District level correlates of COVID-19 pandemic in India during March-October 2020.
COVID-19 is affecting the entire population of India. Understanding district level correlates of the COVID-19's infection ratio (IR) is essential for formulating policies and interventions. The present study aims to investigate the district level variation in COVID-19 during March-October 2020. The present study also examines the association between India's socioeconomic and demographic characteristics and the COVID-19 infection ratio at the district level. We used publicly available crowdsourced district-level data on COVID-19 from March 14, 2020, to October 31, 2020. We identified hotspot and cold spot districts for COVID-19 cases and infection ratio. We have also carried out two sets of regression analysis to highlight the district level demographic, socioeconomic, household infrastructure facilities, and health-related correlates of the COVID-19 infection ratio. The results showed on October 31, 2020, the IR in India was 42.85 per hundred thousand population, with the highest in Kerala (259.63) and the lowest in Bihar (6.58). About 80 percent infected cases and 61 percent deaths were observed in nine states (Delhi, Gujarat, West Bengal, Uttar Pradesh, Andhra Pradesh, Maharashtra, Karnataka, Tamil Nadu, and Telangana). Moran's- I showed a positive yet poor spatial clustering in the COVID-19 IR over neighboring districts. Our regression analysis demonstrated that percent of 15-59 aged population, district population density, percent of the urban population, district-level testing ratio, and percent of stunted children were significantly and positively associated with the COVID-19 infection ratio. We also found that, with an increasing percentage of literacy, there is a lower infection ratio in Indian districts. The COVID-19 infection ratio was found to be more rampant in districts with a higher working-age population, higher population density, a higher urban population, a higher testing ratio, and a higher level of stunted children. The study findings provide crucial information for policy discourse, emphasizing the vulnerability of the highly urbanized and densely populated areas.


Peripartum colloid osmotic pressures: correlation with serum proteins.
Colloid osmotic pressure is a principal regulator of capillary fluid exchange. Alterations in colloid osmotic pressure in preeclamptic patients, as well as significant peripartum changes in colloid osmotic pressure in normotensive patients, are reported. In a study of 72 normotensive and preeclamptic patients, peripartum colloid osmotic pressure, serum albumin, and total serum protein were compared. Both groups exhibited significantly lower colloid osmotic pressure in the postpartum period than that measured antepartum. The mean antepartum colloid osmotic pressure in preeclamptic patients was significantly lower than in normotensive subjects. Regression equations were calculated [colloid osmotic pressure = 5.21 (total serum protein) -11.4 (r2 = 0.851)] and [colloid osmotic pressure = 8.1 (serum albumin) -8.2 (r2 = 0.891)]. Within the physiologic ranges most commonly reported for normotensive and preeclamptic patients, the use of these equations allowed calculation of colloid osmotic pressure to within 10% of measured values in 75 and 80% of the cases, respectively. Where direct measurement of colloid osmotic pressure is not readily available, calculated values may be helpful in patient management.


Transplant uretero-inguinal hernia resulting in urosepsis.
Uretero-inguinal hernias are rare and can be difficult to diagnose. We present a case of a rare transplant kidney uretero-inguinal hernia. An 81-year-old male presented with urosepsis and was found to have an obstructed transplanted kidney secondary to herniation of the ureter into an inguinal hernia. The patient required interventional radiology decompression of the urinary system with a percutaneous nephrostomy tube. In this case, the patient's uretero-inguinal hernia was the extraperitoneal subtype allowing the diagnosis to be made easily on computed tomography imaging of the abdomen and pelvis which facilitated rapid treatment.


Replica symmetry broken states of some glass models.
We have studied in detail the M-p balanced spin-glass model, especially the case p=4. These types of model have relevance to structural glasses. The models possess two kinds of broken replica states; those with one-step replica symmetry breaking (1RSB) and those with full replica symmetry breaking (FRSB). To determine which arises requires studying the Landau expansion to quintic order. There are nine quintic-order coefficients, and five quartic-order coefficients, whose values we determine for this model. We show that it is only for 2≤M<2.4714⋯ that the transition at mean-field level is to a state with FRSB, while for larger M values there is either a continuous transition to a state with 1RSB (when M≤3) or a discontinuous transition for M>3. The Gardner transition from a 1RSB state at low temperatures to a state with FRSB also requires the Landau expansion to be taken to quintic order. Our result for the form of FRSB in the Gardner phase is similar to that found when 2≤M<2.4714⋯, but differs from that given in the early paper of Gross et al. [Phys. Rev. Lett. 55, 304 (1985)0031-900710.1103/PhysRevLett.55.304]. Finally we discuss the effects of fluctuations on our mean-field solutions using the scheme of Höller and Read [Phys. Rev. E 101, 042114 (2020)2470-004510.1103/PhysRevE.101.042114] and argue that such fluctuations will remove both the continuous 1RSB transition and discontinuous 1RSB transitions when 8>d≥6 leaving just the FRSB continuous transition. We suggest values for M and p which might be used in simulations to confirm whether fluctuation corrections do indeed remove the 1RSB transitions.


Endophytic fungal assemblage in Achyranthes aspera Linn. revealed by internal transcribed spacer region of nuclear ribosomal RNA genes.
Only scanty reports are available on endophytic fungal associations in Achyranthes aspera Linn. Hence in this study a total of 504 isolates belonging to ten different species of fungi were isolated from asymptomatic, surface sterilised segments of leaf, stem and root of A. aspera collected from different locations of Kerala, India. Among the isolates ascomycetes were most prevalent. Colonisation rate of fungal endophytes was high in leaf tissue (95%) followed by stem (77.75%) and root segments (33.33%). The most frequent and dominant coloniser of the host plant were Colletotrichum sp., which was isolated from all locations. Scanning electron microscopy demonstrated the presence of hyphae in the intra and intercellular spaces of the plant tissue. Morphological and phylogenetic analyses using internal transcribed spacer (ITS) sequences of nuclear rRNA genes showed that the fungi recovered belonged to the lineages of Sordariomycetes, Dothideomycetes, Eurotiomycetes and Tremellomycetes. A maximum likelihood tree revealed the relationship between the obtained sequence data and the closest sequences retrieved from the GenBank.


Morphological alteration of the pancreatic islet in ovariectomized rats fed a high-fat high-fructose diet.
Diabetes and its complications are major causes of mortality worldwide. Type 2 diabetes coexists with insulin resistance and β-cell dysfunction, which are aggravated by overconsumption and estrogen-deprived conditions. However, the morphology of pancreatic islets in a combined condition of excessive caloric intake and estrogen deficiency has never been described. Herein, we examined morphological changes in the pancreatic islets of ovariectomized (OVX) rats fed a high-fat high-fructose diet (HFFD) for 12 weeks. The histological changes in the size and number of pancreatic islets were assessed by hematoxylin-eosin and immunohistochemical staining. Enlarged pancreatic islets with fat deposition in OVX rats were accompanied by whole-body insulin resistance and hyperglycemia. The addition of a HFFD to OVX rats (OVX + HFFD) further aggravated insulin resistance, with a substantial increase in the density of enlarged pancreatic islets and fat accumulation. The augmented number of enlarged islets was correlated with elevated plasma glucose and insulin levels. Intriguingly, unlike the HFFD and OVX alone, the OVX + HFFD markedly expanded the area of insulin-producing β-cells and glucagon-producing α-cells. Importantly, enlarged islets, pancreatic fat deposits, and diabetic states developing in OVX + HFFD conditions were resolved by estrogen replacement. Collectively, the morphological characteristics of pancreatic islets were influenced in an insulin-resistant state caused by estrogen deficiency and HFFD consumption and were distinct from each factor alone. A combination of estrogen deficiency with HFFD consumption worsened the integrity of pancreatic islets, ultimately resulting in disease progression. These findings expand our understanding of the causal relationship between pancreatic morphology and diabetes development and suggest therapeutic strategies.


[Changes in cardiorhythm and its stochastic parameters in first-graders with normal neuropsychological development and in children with speech disorders during performance of intellectual activity].
Influence of positive and negative motivation on the performance efficiency and some stochastic characteristics of RR-interval fluctuations in speech association experiment was studied in two groups of pupils of the first class: normally developing children and children with speech deviations. It was shown that children with normal development achieve their maximal productivity mostly under the influence of their inner motivation without external stimulation, while for achieving the maximal productivity by children with speech deviations the positive external motivation is required. Baseline ECG recordings in two groups of children significantly differed only in the standard error of the RR-intervals that was decreased in the deviant children. Under conditions of positive motivation, the maximal intellectual productivity in both groups of children was achieved at significantly different values of the fractal index beta. The findings are discussed in terms of the influence of motivation on the verbal performance and concomitant adaptation.


Medication for opioid use disorder treatment continuity post-release from jail: A qualitative study with community-based treatment providers.
People released from jail are at elevated opioid overdose risk. Medications for opioid use disorder (MOUD) are effective in reducing overdoses. MOUD treatment was recently mandated in seven Massachusetts jails, but little is known about barriers and facilitators to treatment continuity post-release. We aimed to assess MOUD provider perspectives on treatment continuity among people released from jail. We conducted qualitative interviews with 36 medical, supervisory, and administrative staff at MOUD programs that serve jail-referred patients. We used the Exploration, Preparation, Implementation, and Sustainment (EPIS) implementation science framework to guide development of instruments, codes, and analyses. We employed deductive and inductive coding, and a grounded theory analytical approach to identify salient themes. Inner context findings highlighted necessary adjustments among jail staff to approve MOUD treatment, especially with agonist medications that were previously considered contraband. Participants perceived that some staff within jails favored abstinence-based recovery, viewing agonists as a crutch. Bridging results highlighted the importance of inter-agency communication and coordination to ensure information transfer for seamless treatment continuity in the community post-release. Pre-release planning, release on pre-scheduled dates, medication provision to cover gaps between jail release and intake at community MOUD sites, and exchange of treatment information across agencies were viewed as paramount to success. Unexpected early releases and releases from court were viewed as barriers to treatment coordination. Outer context domains were largely tied to social determinants of health. Substantial barriers to treatment continuity included shelter, food security, employment, transportation, and insurance reactivation. Through qualitative interviews with community-based MOUD staff, we identified salient barriers and facilitators to treatment continuity post-release from jails. Findings point to needed investments in care coordination, staffing, and funding to strengthen jail-to-community-based MOUD treatment, removing barriers to continuity, and decreasing opioid overdose deaths during this high-risk transition.


Enhancement of tubular organic base accumulation in renal cortical slices by repeated administrations of Tris-hydroxymethyl aminomethane, tromethamol (THAM) to rats of different ages.
After repeated THAM administrations to rats of different ages, an enhancement of THAM accumulation in renal cortical slices was observed, except in newborns. This effect can be interpreted as a specific substrate stimulation of the organic base transport system.


Human induced pluripotent stem cell (hiPSC) line UOMi006-A derived from PBMCs of a patient with Kearns-Sayre syndrome.
Induced pluripotent stem cell (iPSC) line was derived from peripheral blood mononuclear cells (PBMCs) of a Kearns-Sayre syndrome (KSS) patient with mtDNA deletion of 4.8 kilobase fragment. KSS is an ultrarare multi-organ disorder and is characterized with (1.1 to 10 kilobase) deletion of mitochondrial DNA (mtDNA) with a frequency of ~1 in 100,000 individuals. Heteroplasmy in PBMCs allowed us to generate an iPSC line with normal mitochondrial DNA that can be used to study therapeutic prospective of iPSC and their derivatives and design future cell replacement therapies.


Dysregulation of bisphosphoglycerate mutase during in vitro maturation of oocytes.
Oxygen is vital for oocyte maturation; however, oxygen regulation within ovarian follicles is not fully understood. Hemoglobin is abundant within the in vivo matured oocyte, indicating potential function as an oxygen regulator. However, hemoglobin is significantly reduced following in vitro maturation (IVM). The molecule 2,3-bisphosphoglycerate (2,3-BPG) is essential in red blood cells, facilitating release of oxygen from hemoglobin. Towards understanding the role of 2,3-BPG in the oocyte, we characterized gene expression and protein abundance of bisphosphoglycerate mutase (Bpgm), which synthesizes 2,3-BPG, and whether this is altered under low oxygen or hemoglobin addition during IVM. Hemoglobin and Bpgm expression within in vivo matured human cumulus cells and mouse cumulus-oocyte complexes (COCs) were evaluated to determine physiological levels of Bpgm. During IVM, Bpgm gene expression and protein abundance were analyzed in the presence or absence of low oxygen (2% and 5% oxygen) or exogenous hemoglobin. The expression of Bpgm was significantly lower than hemoglobin when mouse COCs were matured in vivo. Following IVM at 20% oxygen, Bpgm gene expression and protein abundance were significantly higher compared to in vivo. At 2% oxygen, Bpgm was significantly higher compared to 20% oxygen, while exogenous hemoglobin resulted in significantly lower Bpgm in the COC. Hemoglobin and 2,3-BPG may play a role within the maturing COC. This study shows that IVM increases Bpgm within COCs compared to in vivo. Decreasing oxygen concentration and the addition of hemoglobin altered Bpgm, albeit not to levels observed in vivo.


MAPK14 over-expression is a transcriptomic feature of polycythemia vera and correlates with adverse clinical outcomes.
The transcriptomic signature has not been fully elucidated in PV, as well as mRNA markers for clinical variables (thrombosis, leukemic transformation, survival, etc.). We attempted to reveal and validate crucial co-expression modules and marker mRNAs correlating with polycythemia vera (PV) by weighted gene co-expression network analysis (WGCNA). The GSE57793/26014/61629 datasets were downloaded from Gene Expression Omnibus (GEO) database and integrated into one fused dataset. By R software and 'WGCNA' package, the PV-specific co-expression module was identified, the pathway enrichment profile of which was obtained by over-representation analysis (ORA). Protein-protein interaction (PPI) network and hub gene analysis identified MAPK14 as our target gene. Then the distribution of MAPK14 expression in different disease/mutation types, were depicted based on external independent datasets. Genome-scale correlation analysis revealed the association of MAPK14 and JAK/STAT family genes. Then gene set enrichment analysis (GSEA) was performed to detect the activated and suppressed pathways associating with MAPK14 expression. Moreover, GSE47018 dataset was utilized to compare clinical variables (thrombosis, leukemic transformation, survival, etc.) between MAPK14-high and MAPK14-low groups. An integrated dataset including 177 samples (83 PV, 35 ET, 17 PMF and 42 normal donors) were inputted into WGCNA. The 'tan' module was identified as the PV-specific module (R2 = 0.56, p = 8e-16), the genes of which were dominantly enriched in pro-inflammatory pathways (Toll-like receptor (TLR)/TNF signaling, etc.). MAPK14 is identified as the top hub gene in PV-related PPI network with the highest betweenness. External datasets validated that the MAPK14 expression was significantly higher in PV than that of essential thrombocytosis (ET)/primary myelofibrosis (PMF) patients and normal donors. JAK2 homozygous mutation carriers have higher level of MAPK14 than that of other mutation types. The expression of JAK/STAT family genes significantly correlated with MAPK14, which also contributed to the activation of oxidated phosphorylation, interferon-alpha (IFNα) response and PI3K-Akt-mTOR signaling, etc. Moreover, MAPK14-high group have more adverse clinical outcomes (splenectomy, thrombosis, disease aggressiveness) and inferior survival than MAPK14-low group. MAPK14 over-expression was identified as a transcriptomic feature of PV, which was also related to inferior clinical outcomes. The results provided novel insights for biomarkers and therapeutic targets for PV.


Identification of an upstream regulatory region essential for cell type-specific transcription of the pro-alpha 2(V) collagen gene (COL5A2).
The transcriptional features of the human alpha 2(V) collagen gene (COL5A2) were examined by transfection experiments coupled to various DNA binding assays. This approach identified an upstream region essential for the cell type-specific expression of the COL5A2 promoter. Within this region are two nuclear factor-binding sites, FP-A and FP-B, responsible for the formation of distinct DNA-protein complexes. Mutations introduced across each of the two binding sites eliminated the formation of the cognate complex and decreased promoter activity by about 3-fold (FP-A) and 40-fold (FP-B) in transfection experiments. Competition experiments using recognition sequences for known transcription factors exhibiting some similarity to the FP-A- and FP-B-binding sites failed to inhibit COL5A2/protein interactions. Thus, COL5A2 expression appears to be under the positive control of a short regulatory sequence likely to harbor two novel nuclear factor-binding sites.


Blockade of ovulation in the rat by systemic and ovarian intrabursal administration of the fungicide sodium dimethyldithiocarbamate.
Dithiocarbamates, acting as inhibitors of catecholamine synthesis, have been reported to block ovulation in female rats following systemic administration by suppressing the neural noradrenergic signaling involved in triggering the ovulatory surge of luteinizing hormone. The ovaries also synthesize norepinephrine and receive noradrenergic input via sympathetic innervation, and it has been suggested that such input may play a role in follicular maturation and ovulation. The current experiments investigated whether the dithiocarbamate fungicide dimethyldithiocarbamate (DMDTC) would block oocyte release in normally cycling rats when administered systemically during the proestrous presurge period, and if so, would the compound also have a comparable direct ovarian effect on ovulation in response to a local intrabursal exposure of one ovary late on the day of vaginal proestrus. The results showed that a dose-related suppression of oocyte release was present in response to both intraperitoneal and intrabursal (IB) injections. But these effects appear to be mediated through different mechanisms. The unilateral IB injections were effective only on the exposed side for each ovarian pair, while no alterations were seen in ovarian norepinephrine. IB administration 24 h earlier blocked ovulation on both sides, while hCG injections were able to restore ovulation on the noninjected side only, implying that diestrous DMDTC was inhibiting the LH surge. The data indicate that while an effect on hypothalamic catecholamine synthesis may underlie the ovulatory blockade following intraperitoneal DMDTC administration, it does not appear to be involved in the response to local ovarian exposure. Moreover, the blockade in response to the diestrous IB exposure likely involves two separate mechanisms, one attributable to an alteration in ovarian hormonal feedback to the brain (or pituitary), inhibiting the LH surge, and the other associated with a direct, as yet undetermined, effect on local preovulatory events within the ovary.


Sex Differences in the Exocrine Pancreas and Associated Diseases.
Differences in pancreatic anatomy, size, and function exist in men and women. The anatomical differences could contribute to the increase in complications associated with pancreatic surgery in women. Although diagnostic criteria for pancreatitis are the same in men and women, major sex differences in etiology are reported. Alcohol and tobacco predominate in men, whereas idiopathic and obstructive etiologies predominate in women. Circulating levels of estrogens, progesterone, and androgens contribute significantly to overall health outcomes; premenopausal women have lower prevalence of cardiovascular and pancreatic diseases suggesting protective effects of estrogens, whereas androgens promote growth of normal and cancerous cells. Sex chromosomes and gonadal and nongonadal hormones together determine an individual's sex, which is distinct from gender or gender identity. Human pancreatic disease etiology, outcomes, and sex-specific mechanisms are largely unknown. In rodents of both sexes, glucocorticoids and estrogens from the adrenal glands influence pancreatic secretion and acinar cell zymogen granule numbers. Lack of corticotropin-releasing factor receptor 2 function, a G protein-coupled receptor whose expression is regulated by both estrogens and glucocorticoids, causes sex-specific changes in pancreatic histopathology, zymogen granule numbers, and endoplasmic reticulum ultrastructure changes in acute pancreatitis model. Here, we review existing literature on sex differences in the normal exocrine pancreas and mechanisms that operate at homeostasis and diseased states in both sexes. Finally, we review pregnancy-related pancreatic diseases and discuss the effects of sex differences on proposed treatments in pancreatic disease.


Systematic review of transanal total mesorectal excision literature according to the ideal framework: The evolution never ends.
Designing studies to assess critically novel procedures can be challenging; thus, the process to achieve robust evidence is frequently problematic. The aim of this systematic review was to evaluate if literature on transanal total mesorectal excision is evolving according to the Idea, Development, Exploration, Assessment, and Long-term results framework. Literature on transanal total mesorectal excision was searched according to the preferred reporting items for systematic reviews and meta-analyses statement, and these variables were recorded: bibliometric data, design, corresponding author's nationality, number of patients enrolled, and Idea, Development, Exploration, Assessment, and Long-term results stages (stage 0, stage 1, stage 2, stage 3, and stage 4). Out of 447 articles retrieved, 247 were selected (76.5% single center and 23.5% multicenter collaborations), including 35 reviews, 15 meta-analyses, 24 other publications, and 173 articles classified according to Idea, Development, Exploration, Assessment, and Long-term results stages (19 stage 0, 27 stage 1, 111 stage 2, 7 stage 3, and 9 stage 4). Overall, impact factor produced was 634.10. Reviewing corresponding authors' nationalities, 32 countries were identified, with the United States, China, and the United Kingdom the most reported; nearly all were from the Northern Hemisphere. Publication of stage 3 and 4 articles started in 2014, whereas stage 0 and 1 articles were stably published over time. The number of patients increased in correspondence with the Idea, Development, Exploration, Assessment, and Long-term results stages (case series with >51 patients, respectively, 100.0% stage 3, 77.8% stage 4, and 33.3% stage 2, P = .005). The number of stage 3 and 4 articles is still low; however, the technical innovation of transanal total mesorectal excision is a non-stop process with preclinical studies stably published over time.


Solid state 19F NMR parameters of fluorine-labeled amino acids. Part I: aromatic substituents.
Structural parameters of peptides and proteins in biomembranes can be directly measured by solid state NMR of selectively labeled amino acids. The 19F nucleus is a promising label to overcome the low sensitivity of 2H, 13C or 15N, and to serve as a background-free reporter group in biological compounds. To make the advantages of solid state 19F NMR fully available for structural studies of polypeptides, we have systematically measured the chemical shift anisotropies and relaxation properties of the most relevant aromatic and aliphatic 19F-labeled amino acids. In this first part of two consecutive contributions, six different 19F-substituents on representative aromatic side chains were characterized as polycrystalline powders by static and MAS experiments. The data are also compared with results on the same amino acids incorporated in synthetic peptides. The spectra show a wide variety of lineshapes, from which the principal values of the CSA tensors were extracted. In addition, temperature-dependent T(1) and T(2) relaxation times were determined by 19F NMR in the solid state, and isotropic chemical shifts and scalar couplings were obtained in solution.


Effect of weight loss by a low-fat diet and a low-carbohydrate diet on peptide YY levels.
To compare the effects of weight loss by an energy-restricted low-fat diet vs low-carbohydrate diet on serum peptide YY (PYY) levels. 8-Week prospective study of 30 obese adults (mean age: 42.8+/-2.0 years, mean body mass index 35.5+/-0.6 kg m(-2)). After 8 weeks, subjects on the low-carbohydrate diet lost substantially more weight than those on the low-fat diet (5.8 vs 0.99 kg, P<0.001). Weight loss by either diet resulted in a 9% reduction in both mean fasting serum PYY levels (baseline: 103.5+/-8.8 pg ml(-1), after weight loss: 94.1+/-6.5 pg ml(-1), P<0.01) and postprandial area under the curve (AUC) PYY (baseline: (20.5+/-1.5) x 10(3) pg h(-1) ml(-1), after weight loss: mean AUC PYY (18.8+/-1.4) x 10(3) pg h(-1) ml(-1), P<0.001). There was a trend towards lower levels of PYY with greater degrees of weight loss. Reduced PYY levels after weight loss by an energy-restricted low-fat or low-carbohydrate diet likely represents a compensatory response to maintain energy homeostasis and contributes to difficulty in weight loss during energy-restricted diets.


Antero-ventral internal pallidum stimulation improves behavioral disorders in Lesch-Nyhan disease.
The Lesch-Nyhan syndrome is an X-linked recessive disorder caused by a deficiency in hypoxanthine-guanine phosphoribosyl transferase, a purine salvage enzyme. Affected individuals exhibit a characteristic neurobehavioral disorder with delayed acquisition of motor skills, dystonia, severe self-mutilations, and aggressive behavior. Deep brain stimulation has been previously proposed for controlling isolated involuntary movements and psychiatric disorders. We applied a double bilateral simultaneous stimulation to limbic and motor internal pallidum in one patient for controlling both behavioral and movement disorders, respectively. The injurious compulsions disappeared; dystonia and dyskinesia were decreased at 28 months follow-up.


Molecular basis of the allelic inheritance of rabbit immunoglobulin VH allotypes: implications for the generation of antibody diversity.
Rabbits are unique in that their immunoglobulin VH regions bear allotypic markers encoded by allelic genes. The presence of these markers on most serum immunoglobulins is difficult to explain, as the germline contains several hundred VH genes. We cloned VH genes from normal rabbits of the VHa allotypes a1, a2, and a3 and from a mutant a2 rabbit, Alicia, which expresses almost no a2 allotype. The D-proximal VH gene VH1 of normal rabbits encoded prototype a1, a2, or a3 allotype VH regions in a1, a2, or a3 rabbits, respectively; VH1 was shown to be preferentially utilized in leukemic rabbit B cells. This VH1 gene was deleted from the germline of the Alicia rabbit. These data suggest that the allelic inheritance of a allotypes results from preferential utilization of VH1 in VDJ rearrangements. We suggest that antibody diversity in rabbit primarily results from somatic hypermutation and gene conversion.


A serum microRNA signature predicts trastuzumab benefit in HER2-positive metastatic breast cancer patients.
Trastuzumab is a standard treatment for HER2-positive (HER2+) breast cancer, but some patients are refractory to the therapy. MicroRNAs (miRNAs) have been used to predict therapeutic effects for various cancers, but whether miRNAs can serve as biomarkers for HER2+ metastatic breast cancer (MBC) patients remains unclear. Using miRNA microarray, we identify 13 differentially expressed miRNAs in the serum of HER2+ MBC patients with distinct response to trastuzumab, and four miRNAs are selected to construct a signature to predict survival using LASSO model. Further, our data show that miR-940 is mainly released from the tumor cells and miR-451a, miR-16-5p and miR-17-3p are mainly from the immune cells. All these four miRNAs directly target signaling molecules that play crucial roles in regulating trastuzumab resistance. In summary, we develop a serum-based miRNA signature that potentially predicts the therapeutic benefit of trastuzumab for HER2+ MBC patients and warrants future validation in prospective clinical trials.


Adjuvant and post-surgical treatment in high-grade epithelial ovarian cancer.
Cytoreductive surgery is the mainstay of treatment for high-grade epithelial ovarian cancer. Although for early stage disease outcomes following surgery alone are good, the risk of recurrence necessitates adjuvant chemotherapy for the majority of patients. Post-operative chemotherapy in advanced-stage disease, or neoadjuvant chemotherapy followed by surgery has improved progression-free survival (PFS) and overall survival (OS). However, despite the use of chemotherapy, the rate of recurrence remains high. In recent years, there has been considerable increase in knowledge regarding the biology of ovarian cancer, which has led to a journey of drug discovery, facilitating the use of novel targeted agents such as VEGF inhibitors and, more recently, PARP inhibitors in the first-line treatment of ovarian cancer. Here, we outline the current evidence-based guidance for systemic therapies in ovarian cancer and highlight the ongoing research to improve patient outcomes.


MALDI-TOF Mass Spectrometry in Clinical Analysis and Research.
In the decade after being awarded the Nobel Prize in Chemistry in 2002, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been widely used as an analytical chemistry tool for the detection of large and small molecules (e.g., polymers, proteins, peptides, nucleic acids, amino acids, lipids, etc.) and for clinical analysis and research (e.g., pathogen identification, genetic disorders screening, cancer diagnosis, etc.). In view of the fast development of MALDI-TOF MS in clinical usage, this review systematically summarizes the most important applications of MALDI-TOF MS in clinical analysis and research by analyzing MALDI TOF MS-related reviews collected in the Web of Science database. On the basis of the analysis of keyword co-occurrence of over 2000 review articles, four themes consisting of "pathogen identification", "disease diagnosis", "nucleic acids analysis", and "small molecules analysis" were found. For each theme, the review further outlined their application implications, analytical methods, and systems as well as limitations that need to be addressed. Overall, the review summarizes and elaborates on the clinical applications of MALDI-TOF MS, providing a comprehensive picture for researchers embarking on MALDI TOF MS-related clinical analysis and research.


Palladium-catalyzed 1,1-alkynylbromination of alkenes with alkynyl bromides.
The palladium-catalyzed 1,1-alkynylbromination of terminal alkenes with a silyl-protected alkynyl bromide is reported. The method tolerates a diverse range of alkenes including vinylarenes, acrylates, and even electronically unbiased alkene derivatives to afford propargylic bromides regioselectively. Mechanistic studies and DFT calculations indicate that the 1,1-alkynylbromination reaction proceeds via the migration of the Pd center followed by the formation of a π-allenyl Pd intermediate, leading to the stereoselective reductive elimination of the C(sp3)-Br bond at the propargylic positon.


Radioiodinated D-(+)-N1-ethyl-2-iodolysergic acid diethylamide: a ligand for in vitro and in vivo studies of serotonin receptors.
Radioiodinated D-(+)-N1-ethyl-2-iodolysergic acid diethylamide ([125I]-EIL) has been evaluated as a ligand for in vitro and in vivo studies of cerebral serotonin 5-HT2 receptors. [125I]-EIL exhibited high affinity (KD = 209 pM) for 5-HT2 receptors with a high degree of specific binding (80-95%) in membranes from rat prefrontal cortex. The regional distribution of [125I]-EIL binding in vivo to seven areas of mouse brain correlated significantly (Rs = 0.93) with known densities of 5-HT2 receptors. In vivo specificity, defined by tissue to cerebellum radioactivity ratios, reached a maximum for frontal cortex at 6 hr (21.2) and persisted through 16 hr (8.8). Ketanserin, a 5-HT2 receptor antagonist, fully inhibited binding in a dose dependent fashion in all brain regions except cerebellum. By contrast, blockers for dopamine D2, alpha- or beta-adrenergic receptors did not significantly inhibit radioligand binding in any region. [125I]-EIL selectively labels 5-HT2 receptors in vivo with the highest specificity of any serotonergic ligand reported to date, indicating that [123I]-EIL should prove applicable to single photon emission computed tomography studies in living brain.


Mixed mycobacterial cultures--occurrence in the clinical laboratory.
During a 2-year period we observed at our institution 22 mixed mycobacterial cultures among a total of 991, representing 20 patients. We found no evidence of double infection. Mixed cultures frequently contained saprophytic organisms. Our experiments have shown that subculturing, especially into liquid media, can significantly change the relative quantities of CFU's present in mixed cultures. We believe that the use of agar media is useful for the recognition of mixed cultures.


Evaluation and management of childhood hypertension.
Hypertension in childhood is diagnosed according to age-adjusted values for each sex. It is more commonly diagnosed now than it was 2 decades ago because blood pressure is more frequently measured in children today. Surgically curable forms of hypertension are not common but usually present as moderate or severe hypertension (diastolic blood pressure greater than or equal to 110 mm Hg). Although many patients in this group are asymptomatic, some present with Bell's palsy, enlarged hearts, heart failure, encephalopathy, or stroke. Newer imaging techniques have proved particularly useful for localizing tumors, such as pheochromocytoma. Many antihypertensive drugs are now available, and therapy should be tailored to the patient's needs, with as few adverse or side effects as possible.


Comparison of the UV/chlorine and UV/H2O2 processes in the degradation of PPCPs in simulated drinking water and wastewater: Kinetics, radical mechanism and energy requirements.
The degradation of pharmaceuticals and personal care products (PPCPs) by the UV/H2O2 and UV/chlorine processes was compared at practical concentrations in simulated drinking water and wastewater. In pure water, the UV/chlorine process performed better than the UV/H2O2 process for the degradation of 16 PPCPs among the investigated 28 PPCPs under neutral conditions. Interestingly, the UV/chlorine approach was superior to the UV/H2O2 approach for the removal of all PPCPs in simulated drinking water and wastewater at the same molar oxidant dosage. The radical sink by oxidants and/or H2O was 2-3 orders of magnitude higher in UV/chlorine than UV/H2O2 in pure water. Thus, the UV/chlorine process was less affected by the water and wastewater matrices than UV/H2O2. In UV/chlorine, the concentration of ClO• was calculated to be ∼3 orders of magnitude greater than that of HO• in pure water, and the reactivities of ClO• with some PPCPs were as high as > 108 M-1 s-1. ClO• was mainly scavenged by the effluent organic matter (EfOM) with a rate constant of 1.8 × 104 (mg L-1)-1 s-1 in wastewater. Meanwhile, secondary radicals such as Br•, Br2•-, ClBr•- and CO3•- further contributed to PPCP degradation by the UV/chlorine process in wastewater, whose concentrations were at least 2 orders of magnitude higher than that in UV/H2O2. Compared with the UV/H2O2 process, the UV/chlorine process saved 3.5-93.5% and 19.1%-98.1% electrical energy per order (EE/O) for PPCP degradation in simulated drinking water and wastewater, respectively.


Studies on biochemical and synergistic effects of immunosuppressive concentration of imidacloprid with Beauveria bassiana and Metarhizium anisopliae for enhancement of virulence against vector mosquito Culex quinquefasciatus.
In order to increase the virulence of two commonly used entomopathogens namely Beauveria bassiana and Metarhizium anisopliae for effective mosquito control programs, we developed new combined formulation by the use of immunosuppressive concentration of imidacloprid. Exposure of sublethal concentration (LC10 1.34 ppb) of imidacloprid to second instar larvae for 92 h that differently modulated the larval biochemical markers by decreasing the total protein (20.65% reduction), acetylcholinesterase (35.74% reduction) and increases the β-carboxylesterase (26.59% increase) and acid phosphatase (30.69% increase) levels while no significant difference was noticed in alkaline phosphatase of C. quinquefasciatus. Further we demonstrated that the imidacloprid exposure brings about reduction in phenoloxidase level (39.48% decrease) and nitric oxide production (37.64% decrease) in larval homogenate over control. The reduction in viability of hemocytes (15.37% decrease) and phagocytic activity of hemocytes (32.18% decrease) was noticed in imidacloprid treatment. Moreover in laboratory condition, exposure of 1 × 107 spores/ml of B. bassiana (984) and M. anisopliae (6060) alone for 92 h cumulative toxicity assay exhibited larval mortality of 36.47% and 47.64% respectively against C. quinquefasciatus. However in the synergistic experimental studies with LC10 of imidacloprid and 1 × 107 spores/ml of B. bassiana or M. anisopliae to the larvae for 92 h cumulative assay brought 60% and 50.59% more insecticidal activity than the respective entomopathogens alone. The substantial increase of larvicidal activity noticed in the synergistic test conditions against larvae of C. quinquefasciatus revealed that the inclusion of sublethal concentration was proved to be useful for effective larval control.


Effects of obovatol on GSH depleted glia-mediated neurotoxicity and oxidative damage.
Earlier studies indicate that obovatol (OBO), isolated from a medicinal herb Magnolia obovata, has anti-inflammatory and anti-oxidative properties. Depletion of glutathione (GSH) in glial cells with the γ-glutamylcysteine synthase inhibitor D,L-buthionine-S,R-sulfoximine (BSO) is known to produce oxidative stress which, in turn, induces these cells to secrete inflammatory cytokines and other neurotoxic substances. In the present study, we investigated the ability of OBO to protect SH-SY5Y neuroblastoma cells from this effect. Human microglia, astrocytes and their surrogate THP-1 and U373 cell lines were activated by treatment with BSO. Such treatment depleted their intracellular GSH and increased levels of damage to DNA, lipids and proteins (8-OHdG, lipid peroxide, protein carbonyls and 3-nitrotyrosine), and activated the inflammatory pathways P38 MAP kinase and NFκB. These are accompanied by release of proinflammatory factors such as TNFα, IL-6 and nitric oxide. Their conditioned media were toxic to SH-SY5Y cells. All these effects were attenuated by pre-treatment with OBO. Prior treatment of SH-SY5Y cells with OBO also attenuated THP-1 or U373 conditioned media neurotoxicity and also reduced oxidative damage produced by treatment with hydrogen peroxide or BSO. Prior treatment with OBO potentiated survival of SH-SY5Y cells exposed to conditioned medium from BSO-treated THP-1, U373 cells, microglia and astrocytes. The data indicate that OBO could be anti-inflammatory, anti-oxidative and neuroprotective, and be an effective agent for inhibiting pathogenesis in neurological diseases such as Alzheimer disease, Parkinson disease and amyotrophic lateral sclerosis in which glial-mediated neuroinflammation and oxidative stress are thought to contribute to disease progression.


Fundal changes in children receiving Vigabatrin.
Visual field defects and other abnormalities are reported in patients receiving the newer antiepileptic Vigabatrin (VGB). Field testing in children younger than 6 years and those with mental retardation is difficult. The authors, therefore, studied ophthalmoscopic abnormalities in seven pediatric patients receiving VGB for median duration of 9 month (range, 3-32 months). Abnormal findings were seen in two (33.3%) in the form of surface wrinkling retinopathy and abnormal macular reflexes. The proportion of abnormal findings was in agreement with previous reports. Thus it is concluded that simple ophthalmoscopy by an ophthalmologist picks up the abnormalities due to ocular toxicity of VGB, and helps in rationalizing further AED therapy in the clinic.


Periodontal disease is related to local and systemic mediators of inflammation.
Local and systemic biomarkers in gingival crevicular fluid increase odds of periodontitis. Fitzsimmons TR, Sanders AE, Bartold PM, Slade GD. J Clin Periodontol 2010;37(1):30-6. Ananda P. Dasanayake, BDS, MPH, PhD, FACE. The authors attempted to study the independent and combined effects of local (IL-1β) and systemic (CRP) inflammatory biomarkers in gingival crevicular fluid (GCF) on the risk of periodontitis. Government: National Health and Medical Research Council (NHMRC) of Australia and NHMRC Sidney Sax Public Health Fellowship. Case-control study. Level 2: Limited-quality, patient-oriented evidence. Not applicable.


The association between eosinophils (CD16+ eosinophils), basophils (CD203+ basophils), and CD23 B lymphocytes in patients with atopic dermatitis on dupilumab therapy: pilot study.
Eosinophils, basophils, and the molecule CD23 on B cells are involved in the pathophysiology of atopic dermatitis (AD). The molecule CD23 is involved in the regulation of IgE synthesis and is expressed by activated B cells. The molecule CD16 is used to assess the activation of eosinophils and CD203 of basophils. The association between the count of eosinophils, basophils, CD16+ eosinophils, CD203+ basophils and the expression of the activation marker CD23 on B cells in patients with AD (with and without dupilumab therapy) is not described. The aim of this pilot study is to evaluate the association between the blood count of eosinophils, basophils, relative CD16+ eosinophils, relative CD203+ basophils, and the expression of molecule CD23 on B cells and on their subsets (total, memory, naive, switched, non-switched) in patients suffering from AD (with and without dupilumab therapy) and in control group. A total of 45 patients suffering from AD were examined; 32 patients without dupilumab treatment (10 men, 22 women, average age 35 years), 13 patients with dupilumab treatment (7 men, 6 women, average age 43.4 years), and 30 subjects as a control group (10 men, 20 women, average age 44.7 years). Immunophenotype was examined by flow cytometry in which monoclonal antibodies with fluorescent molecules were used. For statistical analysis we used non-parametric Kruskal-Wallis one-factor analysis of variance with post hoc by Dunn's test with Bonferroni modification and the Spearman's rank correlation coefficient; for coefficients higher than 0.41, we report R2 (percent of variation explained). The absolute count of eosinophils was significantly higher in patients with AD (with and without dupilumab) in comparison to healthy subjects. The difference in the relative count of CD16+ eosinophils in patients with AD (with and without dupilumab therapy) compared with control is not statistically significant. In patients with dupilumab therapy the significantly lower count of relative CD203+ basophils was confirmed compared with control. The higher association between the count of eosinophils (absolute and relative) and the expression of CD23 marker on B cells was confirmed in patients with dupilumab therapy; in contrast, this association was low in patients with AD without dupilumab therapy and in healthy subjects. The higher association between the count of eosinophils (absolute and relative) and the expression of CD23 marker on B cells was confirmed in patients with AD under dupilumab therapy. It suggests that IL-4 production by eosinophils may play a role in B lymphocyte activation. The significantly lower count of CD203+ basophils has been demonstrated in patients with dupilumab therapy. This reduction of CD203+ basophil count may contribute to the therapeutic effects of dupilumab by reducing the inflammatory response and allergic reactions in patients with AD.


Implication of VEGF and aquaporin 4 mediating Müller cell swelling to diabetic retinal edema.
Aquaporin 4 (AQP4), a water channel protein, is known to be expressed in retinal Müller cells. The purpose of this study was to determine the effects of VEGF and AQP4 channels on the volumetric changes in Müller cells. Retinas from diabetic rats and a cultured Müller cell line, TR-MUL5, were used in this study. Intravitreal injections of VEGF or PBS were performed on either streptozotocin (STZ)-induced diabetic or normoglycemic rats. Retinal sections were immunostained for anti-glial fibrillary acidic protein (GFAP), anti-AQP4, and anti-VEGF. VEGF protein levels from collected retinas were determined by western blot analysis. Volumetric changes and nitric oxide (NO) levels in cultured Müller cells were determined using flow cytometry (FACS), in the presence or absence of VEGF and TGN-020, a selective AQP4 inhibitor. In the diabetic rat retina, VEGF immunoreactivity was concentrated in the internal retinal layers, and AQP4 immunoreactivity was higher than controls. The expressions of AQP4 were colocalized with GFAP. Protein levels of VEGF in the hyperglycemic rat retina were significantly higher than controls. FACS analyses showed that exposure to VEGF enlarged Müller cells, while exposure to TGN-020 suppressed the enlargement. Intracellular levels of NO were increased after exposure to VEGF, which was suppressed following the addition of TGN-020. The observed Müller cell swelling is mediated by VEGF and AQP4.


Expressed STSs and transcription of human Xq28.
STSs, which have been used to build and format clone contigs, have been used here to assemble a transcriptional map across a cytogenetic band. Of fifty one STSs in Xq28, 20 were positive by RT-PCR. Thus, an additional 20 possible ESTs were detected among the STSs, and seven of these also identified cDNAs in at least one library. The transcripts confirm the high expression level of this region, correlated with its GC compositional map and CpG island content.


Lymphocyte function in the critically ill surgical patient.
Lymphocyte function is commonly altered in critical ill surgical patients. There is controversy whether or not formation of antibodies is impaired; however, cellular immune responses are routinely depressed. Patients who have suffered major surgical or accidental trauma or burns frequently become anergic. Their lymphocytes respond poorly to mitogenic or antigenic stimulation, and serum factors suppressive of lymphocyte activation appear. Mechanisms underlying these abnormalities remain to be defined.


Infliximab monotherapy provides rapid and sustained benefit for plaque-type psoriasis.
Effective, rapid-acting, safe therapies are needed for the long-term treatment of psoriasis. We sought to evaluate infliximab monotherapy in maintaining clinical benefit in psoriasis. A total of 33 patients received 3 doses of 5 or 10 mg/kg of infliximab or placebo at weeks 0, 2, and 6 (double-blind phase). During the open-label phase (weeks 10-26), responding patients were evaluated for relapse (loss of at least half of the improvement in the Psoriasis Area Severity Index score at week 10) and retreated with open-label infliximab (5 or 10 mg/kg) as needed. Placebo nonresponders were treated with an induction regimen of infliximab (5 or 10 mg/kg) and followed up through week 26. In all, 29 patients received either 5 or 10 mg/kg of infliximab in the open-label extension. At week 26, psoriasis area severity index response was maintained in 40% and 73% of patients receiving 5 and 10 mg/kg of infliximab, respectively. Infliximab produced a rapid, effective, and sustainable (through week 26) effect in patients with moderate to severe psoriasis.


Downregulation of Mad2 and BubR1 increase the malignant potential and nocodazole resistance by compromising spindle assembly checkpoint signaling pathway in cervical carcinogenesis.
To explore the involvement of Mad2 and BubR1 in cervical carcinogenesis. The expressions of Mad2 and BubR1 in tissues of high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL) and chronic cervicitis were analyzed immunohistochemistrily and compared with those of p16INK4A . PEGFP-Mad2 and pEGFP-BubR1 were transfected into SiHa cells to overexpress Mad2 and BubR1 and Si-RNAs to knockdown. Cell viability was measured by cell counting kit-8 (CCK-8) assay. Migration and invasion capabilities were detected by Transwell. Propidium iodide staining with flow cytometry was used for cell cycle analysis and apoptosis was detected using Annexin V/7-AAD staining after nocodazole treatment. The expression of Mad2 was significantly lower in HSIL than those in chronic cervicitis and LSIL, however, the expression of BubR1 showed no significant differences. To detect HSIL in cervical lesions, Mad2 had a sensitivity of 88.44% and a specificity of 87.23%, Mad2 was less sensitive and more specific than p16INK4a . In SiHa cells, knockdown of Mad2 and BubR1 increased cell growth, reinforced invasion capacity and migration potency, inhibited apoptosis and decreased G2-phase distribution after nocodazole treatment. Oppositely, the overexpression strategies made cells show decreased malignant behaviors, raised apoptosis and increased G2-phase distribution. Mad2 negativity was specific to identify HSIL immunohistochemistrily. Downregulation of Mad2 and BubR1 increase the malignant behavior and nocodazole resistance of SiHa cells via causing spindle assembly checkpoint defect. This mechanism may contribute to cervical carcinogenesis and resistance to microtubule-targeting drugs.


Analysis of growth hormone receptor gene expression in tall and short stature children.
The majority of children who present for evaluation of tall stature fall under the diagnosis of constitutional tall stature (CTS). To investigate mechanisms of tall stature, we evaluated serum IGF-I values and the expression of the GHR gene in the peripheral blood cells of 46 subjects with normal height, 38 with tall stature and 30 healthy children with short stature. Our results showed significantly lower IGF-I levels in children with short stature (-0.57±0.18 SDS) compared to control children (0.056±0.19 SDS; p<0.0001) and to subjects with tall stature (0.594±0.17; p=0.00067). Furthermore, we found significantly higher GHR gene expression levels in tall children (321.84±90.04 agGHR/5×105agGAPDH) compared with other groups of subjects (short children: 30.13±7.5 agGHR/5×105agGAPDH, p<0.0001; controls: 86.81ag±19.5 GHR/5×105agGAPDH, p=0.035). The GHR gene expression level in short children was significantly lower compared with control subjects (p=0.0068). Significantly higher GHR gene expression levels in tall subjects suggests a sensitization of the GHR-IGF system leading to overgrowth in CTS.


Building an empowerment policy paradigm: self-reported strengths of homeless mothers.
Self-reported strengths and goals of a sample of 64 mothers of young children residing in a temporary shelter for homeless families, were documented. The strengths most frequently reported included ability to take action, parental competence, and determination in the face of stress. Program and policy implications of these positive attributes of homeless mothers are discussed.


Conjugating MMAE to a novel anti-HER2 antibody for selective targeted delivery.
To investigate the target delivery properties of RC48-ADC, a novel antibody drug conjugate (ADC) comprising cytotoxic monomethyl auristatin E (MMAE) and an anti-human epidermal growth factor receptor 2 (HER2) antibody tethered via valine-citrulline linker, in vitro and in vivo. Dissociation rate of MMAE from RC48-ADC was used as an estimate of its stability in serum. Cytotoxicity of the antibody and RC48-ADC towards multiple cell lines was measured. Subcellular distribution of the drug was determined by fluorescence imaging. The mechanism of lysosome targeting was verified. Endocytic pathways of RC48-ADC were assessed by the cellular fluorescence intensity of fluorescently-labelled drugs. Intracellular and extracellular distribution of MMAE was analysed after RC48-ADC or MMAE administration to characterize MMAE release. The serum and tumour concentration of MMAE was compared after tail-vein injection of RC48-ADC into tumour-bearing mice. RC48-ADC was highly stable in human serum. HER2-overexpressed cell line SK-BR-3 proliferation was stronger when suppressed by RC48-ADC than by the naked antibody. Both RC48-ADC and naked antibody were internalized via caveolae-mediated and clathrin-mediated endocytosis and concentrated in lysosomes. Higher HER2 expression was associated with enhanced uptake and intracellular release of conjugated MMAE; free MMAE could kill tumour cells via the bystander effect. Although serum RC48-ADC concentration was higher than that in tumours, exposure of MMAE in tumours was ~200 times higher than in serum, which rationalized the reduced toxicity of RC48-ADC. In vitro and in vivo experiments confirmed the targeted transport and release of RC48-ADC; it could selectively deliver MMAE to the targeted HER2-positive cell or tumour tissue, which could reduce off-target toxicity and enhance anti-tumour potency in humans.


[Close teamwork between pathologist and surgeon can improve results in colorectal cancer treatment].
Colorectal cancer is common in the Western world and is a leading cause of cancer related mortality. The introduction of multidisciplinary teams and focus on quality control has led to improved outcomes in which pathologists play a central role through feedback to surgeons, radiologists, and oncologists. This review focuses on the importance of pathological examination of the resection specimen and subsequent feedback to the surgical team regarding quality. Specific markers of oncological quality including grading the plane of surgery, tissue morphometry and lymph node yields are discussed.


3, 3'- (3, 5-DCPBC) Down-Regulates Multiple Phosphokinase Dependent Signal Transduction Pathways in Malignant Melanoma Cells through Specific Diminution of EGFRY1086 Phosphorylation.
Melanoma is the most dangerous skin malignancy due to its strong metastatic potential with high mortality. Activation of crucial signaling pathways enforcing melanoma progression depends on phosphorylation of distinct tyrosine kinases and oxidative stress. We here investigated the effect of a bis-coumarin derivative [3, 3'- ((3″, 5'-Dichlorophenyl) methylene) bis (4-hydroxy-2H-chromen-2-one)] [3, 3'- (3, 5-DCPBC)] on human melanoma cell survival, growth, proliferation, migration, intracellular redox state, and deciphered associated signaling pathways. This derivative is toxic for melanoma cells and non-toxic for melanocytes, their benign counterpart, and fibroblasts. 3, 3'- (3, 5-DCPBC) inhibits cell survival, migration, and proliferation of different metastatic and non-metastatic melanoma cell lines through profound suppression of the phosphorylation of Epidermal Growth Factor receptor (EGFR) and proto-oncogene cellular sarcoma (c-SRC) related downstream pathways. Thus, 3, 3'- (3, 5-DCPBC) endowed with the unique property to simultaneously suppress phosphorylation of multiple downstream kinases, such as EGFR/JAK/STAT and EGFR/SRC and their corresponding transcription factors.


Comparative genetics and innate immune functions of collagenous lectins in animals.
Collagenous lectins such as mannan-binding lectins (MBLs), ficolins (FCNs), surfactant proteins A and D (SP-A, SP-D), conglutinin (CG), and related ruminant lectins are multimeric proteins with carbohydrate-binding domains aligned in a manner that facilitates binding to microbial surface polysaccharides. MBLs and FCNs are structurally related to C1q, but activate the lectin complement pathway via interaction with MBL-associated serine proteases (MASPs). MBLs, FCNs, and other collagenous lectins also bind to some host macromolecules and contribute to their removal. While there is evidence that some lectins and the lectin complement pathway are conserved in vertebrates, many differences in collagenous lectins have been observed among humans, rodents, and other vertebrates. For example, humans have only one MBL but three FCNs, whereas most other species express two FCNs and two MBLs. Bovidae express CG and other SP-D-related collectins that are not found in monogastric species. Some dysfunctions of human MBL are due to single nucleotide polymorphisms (SNPs) that affect its expression or structure and thereby increase susceptibility to some infections. Collagenous lectins have well-established roles in innate immunity to various microorganisms, so it is possible that some lectin genotypes or induced phenotypes influence resistance to some infectious or inflammatory diseases in animals.


The upper airway in sleep-disordered breathing: a clinical prediction model.
An examination of the upper airway in patients with suspected sleep disordered breathing (SDB) is recommended prior to nighttime polysomnography (PSG) despite a reported low predictive value of those examinations. The aim of this study was to evaluate the data of the clinical examination and to create a clinical prediction model. Retrospective cohort study. A recently introduced method of dynamic examination of the upper airway during simulated snoring (SS) in awake patients is conducted in patients with suspected SDB. Clinical parameters, body mass index (BMI), and the Epworth sleepiness scale (ESS) scores of 622 patients were included in a clinical prediction model and correlated to the apnea-hypopnea index (AHI). A correlation was detected between the AHI and alterations of the upper airway during SS, BMI, and ESS score. A clinical prediction model including clinical data, BMI, and ESS score revealed a high sensitivity but low specificity predicting the nocturnal AHI: calculated AHI = tonsil size x 2.648 + uvula size x 3.776 + dorsal movement during SS x 2.842 + collapse at tongue base level during SS x 4.769 + BMI x 0.609 + ESS score x 1.177 - 27.685. The dynamic examination of the upper airway during SS in awake patients in combination with clinical data, the BMI, and ESS score is an easy-to-perform screening procedure prior to nighttime PSG and might support the otorhinolaryngologic diagnostic approach in patients with suspected SDB.


Vitamin C preserves endothelial function in patients with coronary heart disease after a high-fat meal.
It has been suggested that an oxidative mechanism is involved with the impaired endothelium-dependent vasodilatation that occurs after a high-fat meal. The study was undertaken to evaluate the effect of a single oral dose of vitamin C (2 g) on postprandially impaired endothelium-dependent vasodilatation in patients with coronary heart disease (CHD). This study included 74 patients with CHD and 50 subjects without CHD with risk factors. The two groups were divided into two subgroups that did or did not receive 2 g of vitamin C (CHD/VitC and CHD/control, n = 37; non-CHD/VitC and non-CHD/control, n = 25) after a high-fat meal (800 calories, 50 g fat). Serum levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in the fasting state and at 2, 4, 5, and 7 h after the high-fat meal were measured. Endothelial function was assessed in the brachial artery by high-resolution ultrasound at baseline and at 4 h postprandially. The postprandial serum triglyceride concentration increased significantly at 2-5 h after the high-fat meal in all groups. The fasting flow-mediated dilatation (FMD) (p < 0.02) and nitroglycerin-induced dilatation (NID) (p < 0.05) of patients with CHD were impaired compared with those of non-CHD subjects. Postprandial FMD was significantly aggravated in the non-CHD/control group (p < 0.01) and the CHD/control group (p < 0.001), but the postprandial FMD in patients and subjects taking vitamin C showed no significant change, although the CHD/VitC group had a mild tendency toward improvement (p = 0.064) and non-CHD/VitC group had a mild tendency toward aggravation (p = 0.852). The change of NID after a high-fat meal did not reach statistical significance in the four groups. The decrement of postprandial FMD correlated positively with the increment of 2-h serum triglyceride concentration in the patients without vitamin C (n = 62, r = 0.545, p < 0.001). The postprandial state after a high-fat meal is critical in atherogenesis, as it induces endothelial dysfunction through an oxidative stress mechanism. Vitamin C treatment has a promising benefit for patients with CHD.


Detection of Toxoplasma gondii in cerebrospinal fluid from AIDS patients by polymerase chain reaction.
The polymerase chain reaction (PCR) was used to detect Toxoplasma gondii DNA in cerebrospinal fluid (CSF) from 14 patients with AIDS by amplification of the repetitive B1 gene. Positive PCRs were obtained in CSF from four of nine patients with toxoplasmic encephalitis. CSF samples from five control patients were negative for T. gondii DNA by PCR.


Recovery of central respiratory function following anticholinesterase intoxication.
Spontaneous recovery of central respiratory function was studied in anesthetized guinea pigs intoxicated with pinacolyl methylphosphonofluoridate (Soman) or isopropyl methylphosphonofluoridate (Sarin). I.v adiministration of either agent produced an immediate disruption phrenic nerve activiity and resulting ventilatory failure. Animals were maintained on artifical respiration until spontaneous functional recovery was complete, as evidenced by the re-establishment of synchronized burst activity on the phrenic nerve and return of tracheal airflow. This usually occurred within 1 h. Animals were sacrificed at predetermined intervals after intoxication, and the brainstem homogenates were analyzed for AChE activity. Results showed no significant return of AChE activity after 1 h, although functional recovery of respiration was complete within this time. Additional doses of the agents were administered at various times after recovery from the respiratory blockade. Following spontaneous restoration of ventilatory function, subsequent injections of the organophosphorus compounds failed to reinstate central respiratory paralysis, although they further depressed brainstem AChE levels. These data suggest that spontaneous recovery of central respiratory function after intoxication with Soman or Sarin may not be related to the return of AChE activity.


Bacteriophage therapy for challenging bacterial infections: achievements, limitations and prospects for future clinical use by veterinary dermatologists.
Bacteriophages were discovered just over 100 years ago and have been used to treat bacterial infections in animals since the 1920s. The antimicrobial resistance crisis has led to a new surge of interest in the use of bacteriophage therapy as an alternative or supplement to antimicrobial therapy in humans and other animals. To describe the nature of bacteriophages and provide a critical review and update on the clinical use of bacteriophages in the treatment of challenging bacterial infections, with an emphasis on companion animal veterinary applications. The scientific literature on the subject was critically evaluated. Findings from the most pertinent papers have been presented in summary form and critiqued. Over the last 20 years there has been a considerable increase in the volume and quality of publications dealing with bacteriophage therapy. Some recent papers build on excellent work published in the 1980s and describe promising veterinary applications. Challenges related particularly to the registration and approval of phage remedies will need to be overcome before phage therapy can become a mainstream tool for use in veterinary settings. Considerably more research, particularly controlled clinical trials, needs to be done. Bacteriophage therapy is one of the most promising approaches to tackling the looming antimicrobial resistance crisis, yet substantial regulatory challenges will need to be overcome before it enters widespread use. Phage therapy also may, in the future, improve the management of challenging bacterial infections that are not necessarily multidrug-resistant.


A recombinant fowl adenovirus expressing the S1 gene of infectious bronchitis virus protects against challenge with infectious bronchitis virus.
The spike peplomer S1 subunit sequence from avian infectious bronchitis virus (IBV) Vic S strain was expressed in a plasmid under the control of the fowl adenovirus (FAV) major late promoter (MLP). Two recombinants were constructed in FAV serotype 8 (FAV 8) by inserting the expression cassette between the SnaBI and XbaI restriction enzyme sites (clone DA3) or between the SpeI sites (clone CA6-20). Expression of the S1 gene in the recombinants was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) by 20h post-infection. Commercial broiler chickens were orally vaccinated at day 0 or day 6 post-hatch and challenged at day 35 post-hatch. FAV antibody ELISA confirmed that maternal antibody directed against inclusion body hepatitis (serotype 8) had decayed in control birds and that FAV specific serum IgG responses were produced in vaccinated birds at the time of challenge. Further, an S1 specific antibody response was detected prior to challenge. Birds were challenged with either Vic S (serotype B) or N1/62 (serotype C) strains of IBV. The tracheas of challenged birds were analyzed by RT-PCR and re-isolation of virus. In birds vaccinated at day 6, 90-100% protection at the trachea was induced against either homologous or heterologous challenge. The construction of a recombinant FAV expressing S1 of IBV demonstrates the potential of an alternative vaccination strategy against IBV.


The choline transporter is the major site of control of choline oxidation in isolated rat liver mitochondria.
The degree of control exerted by the mitochondrial choline transporter over the oxidation pathway was measured in isolated rat liver mitochondria. Choline transporter activity was titrated with hemicholinium-3, a known competitive inhibitor of the transporter. It was shown that the rate of betaine efflux from mitochondria was an accurate measure of choline oxidation. The relative rate of choline oxidation was measured as a function of the relative degree of inhibition of the transporter. The resulting data gave a flux control coefficient over choline oxidation of 0.9 for the choline transporter. It is concluded that the choline transporter is the major site for control of choline oxidation in isolated rat liver mitochondria.


Impact of epidural analgesia on quality of life and pain in advanced cancer patients.
Patients with advanced cancer often experience chronic postoperative pain and poor quality of life. The objective of this study was to determine if epidural self-controlled analgesia reduced the incidence of chronic pain and improved the quality of life when compared with intravenous self-controlled analgesia. A total of 50 patients diagnosed with advanced cancer who received analgesia treatment were randomly divided into two groups, epidural self-controlled analgesia group (EA group, n = 26) and intravenous self-controlled analgesia group (IA group, n = 24). Visual analog scale (VAS) and Karnofsky score were used to assess the pain and the quality of life, respectively. A multifunction monitor was used to continuously record the physical signs of patients after treatment. The physical signs, such as heart failure, respiration, pulse, blood pressure, and oxygen saturation, in the two groups were better after analgesia treatment. Meanwhile, the respiration and oxygen saturation in the EA group were significantly improved compared with that of the IA group (p < .05). The VAS in the EA group was significantly lower than that in the IA group (p < .05), and the Karnofsky score in the EA group was significantly higher than that in the IA group (p < .05). Moreover, patients treated with EA felt more satisfied and experienced fewer complications than those with IA (p < .05). The epidural self-controlled analgesia may greatly improve the quality of life and relieve the pain in patients with advanced cancer.


Management of angle-closure glaucoma with X-linked retinoschisis: a case report.
X-linked retinoschisis (XLRS), due to mutations in the RS1 gene, is a common genetically determined form of macular degeneration. This report describes an unusual case of angle-closure glaucoma (ACG) with XLRS and discusses the treatment. A 39-year-old Chinese man with an X chromosome-recessive inherited c.489G > A variant in the RS1 gene was diagnosed as XLRS and ACG, presenting with cystic macular lesions, shallow anterior chamber depth (ACD), and angle-closure with uncontrolled intraocular pressure (IOP). Malignant glaucoma occurred following trabeculectomy combining phacoemulsification with intraocular lens (IOL) implantation and goniosynechialysis. Subsequent anterior vitrectomy and irido-zonulo-hyaloid-vitrectomy (IZHV) effectively lowered IOP and deepened ACD, but the cystic cavity became larger. There is a potential risk of malignant glaucoma in ACG patients with XLRS after filtering surgery. Although anterior vitrectomy can effectively resolve aqueous misdirection, the macular retinoschisis may get worse. Awareness of this risk may aid in surgical planning and postoperative management in these patients.


A model for obstructive sleep apnea detection using a multi-layer feed-forward neural network based on electrocardiogram, pulse oxygen saturation, and body mass index.
To develop and evaluate a model for obstructive sleep apnea (OSA) detection using an artificial neural network (ANN) based on the combined features of body mass index (BMI), electrocardiogram (ECG), and pulse oxygen saturation (SpO2). Polysomnography (PSG) data for 148 patients with OSA and 33 unaffected individuals were included. A multi-layer feed-forward neural network (FNN) was used based on the features obtained from ECG, SpO2, and BMI. The receiver operating characteristic (ROC) curve and the metrics of accuracy, sensitivity, and specificity were used to evaluate the performance of the overall classification. Some other machine learning methods including linear discriminant, linear Support Vector Machine (SVM), Complex Tree, RUSBoosted Trees, and Logistic Regression were also used to compare their performance with the FNN. The accuracy, sensitivity, and specificity of the proposed multi-layer FNN were 97.8%, 98.6%, and 93.9%, respectively, and the area under the ROC curve was 97.0%. Compared with the other machine learning methods mentioned above, the FNN achieved the highest performance. The satisfactory performance of the proposed FNN model for OSA detection indicated that it is reliable to screen potential patients with OSA using the combined channels of ECG and SpO2 and also taking into account BMI. This strategy might be a viable alternative method for OSA diagnosis.


Immunostimulatory probiotic Lactobacillus rhamnosus HN001 and Bifidobacterium lactis HN019 do not induce pathological inflammation in mouse model of experimental autoimmune thyroiditis.
The possibility that intestinal microflora contribute to the pathogenesis of autoimmune diseases has raised issues regarding the safety of probiotic organisms, especially those with immunostimulating properties, in individuals with such immune dysfunctions. In this study, the effect of consumption of probiotic lactic acid bacteria (LAB) strains Lactobacillus rhamnosus HN001(HN001) and Bifidobacterium lactis HN019 (HN019) on the induction and progression of experimental autoimmune thyroiditis (EAT) was investigated in CBA/CaH (H-2k) mice. HN001 or HN019 in skim milk were fed to mice daily (1-1.5 x 10(8) cfu/mouse/day) for 5 to 9 weeks. A mild form of EAT was induced by subcutaneous injection of mouse thyroglobulin (MTg) with either Freund's adjuvant (complete and incomplete, CFA and IFA) or lipopolysaccharide (LPS). The proliferative responses of spleen lymphocyte to MTg stimulation in vitro and the presence (and degree) of mononuclear cell infiltration in thyroid gland tissues were examined to assess the development and severity of EAT. The levels of serum anti-MTg antibodies (IgG1 and IgG2a) and spleen weight index were determined to detect the presence of autoimmune responses of mice receiving MTg. Results showed that 8 weeks after immunization, 16.67-50% of the mice developed mild EAT with lymphocyte infiltration in the thyroid glands. Probiotic feeding did not induce full-blown EAT. There were no differences in spleen weight index or the proliferative spleenocytes in response to PMA between mice that received MTg alone and mice that received MTg and probiotic LAB strains.


Multiple basal cell carcinoma in tropical Australia.
No association between HLA DR1 and the development of multiple basal cell carcinomas (BCC) was found among patients who had lived at least two-thirds of their lives in the tropics. The percentage of patients with multiple BCCs increased with age; this was different from what has been found in people living in the temperate zone of Australia.


Historical narrative from fatty liver in the nineteenth century to contemporary NAFLD - Reconciling the present with the past.
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder worldwide. This historical narrative traces the evolution from basic descriptions of fatty liver in the nineteenth century to our contemporary understanding of NAFLD in the twentieth and twenty-first centuries. A detailed historiographic review of fatty liver from 1800s onwards was performed alongside a brief review of contemporary associations. Archived published literature dating back to the 1800s describe clinicopathological features of fatty liver. In the nineteenth century, doyens of medicine associated fatty liver with alcohol, malnutrition or wasting conditions, and subsequently adiposity, unhealthy diets and sedentary lifestyle. Microscopically, fatty liver was described when 5% or more hepatocytes were distended with fat. Recommendations to reverse fatty liver included reducing consumption of fat, sugar, starchy carbohydrates and alcohol, plus increasing physical exercise. Fatty liver was associated with liver fibrosis and cirrhosis in the late 1800s, and with diabetes in the early 1900s. The diagnostic labels NAFLD and non-alcoholic steatohepatitis (NASH) were introduced in the late 1900s. Metabolic dysfunction-associated fatty liver disease (MAFLD) was recently proposed to update the nosology of fatty liver, recognising the similar metabolic pathogenesis evident in individuals with typical NAFLD and those with heterogenous "secondary" co-factors including alcohol and other aetiologies. Fatty liver has emerged from being considered a disorder of nutritional extremes or alcohol excess to contemporary recognition as a complex metabolic disorder that risks progression to cirrhosis and hepatocellular carcinoma. The increasing prevalence of NAFLD and our growing understanding of its lifestyle and metabolic determinants justify the current exercise of re-examining the evolution of this common metabolic disorder.


[Dehiscence of anastomosis in surgery of the colon. Causes and prevention].
150 operations on the large intestine performed in 1976-81 are presented with the percentage of dehiscences following surgery. In considering the problem of fistulas arising on the colonic sutures, the more frequent aetiopathogenetic factors are examined. The percentages reported are compared with those produced by the best medical schools. Curves recommended in recent literature are also reported.


The hsp70 inhibitor VER155008 induces paraptosis requiring de novo protein synthesis in anaplastic thyroid carcinoma cells.
In this study, we evaluated the effect of the hsp70 inhibitor VER155008 on survival of anaplastic thyroid carcinoma (ATC) cells. In ATC cells, VER155008 increased the percentages of dead cells and vacuolated cells. VER155008 did not lead to the cleavage of caspase-3 protein regardless of pretreatment with z-VAD-fmk. VER155008 increased LC3-II protein levels but the protein levels were not changed by autophagy inhibitors. VER155008 caused the dilatation of endoplasmic reticulum (ER), and the increased mRNA levels of Bip and CHOP, suggesting paraptosis. VER155008-induced paraptosis was attenuated by pretreatment with cycloheximide. In conclusion, VER155008 induces paraptosis characterized by cytoplasmic vacuolation, independence of caspase, dilatation of ER and induction of ER stress markers in ATC cells. Moreover, VER155008-induced paraptosis requires de novo protein synthesis in ATC cells.


Genetic analysis of metabolic defects in the spontaneously hypertensive rat.
Abnormalities in carbohydrate and lipid metabolism are common in patients with essential hypertension and in the spontaneously hypertensive rat (SHR). To identify chromosome regions contributing to this clustering of cardiovascular risk factors in the SHR, we searched for quantitative trait loci (QTL) associated with insulin resistance, glucose intolerance, and dyslipidemia by using the HXB/BXH recombinant inbred (RI) strains. Analysis of variance in RI strains suggested significant effects of genetic factors. A genome screening of the RI strains with more than 700 markers revealed QTL significantly associated with insulin resistance on Chromosomes (Chrs) 3 and 19. The Chr 19 QTL was confirmed by testing a previously derived SHR-19 congenic strain: transfer of a Chr 19 segment delineated by markers D19Rat57 and D19Mit7 from the Brown Norway (BN/Cr) strain onto the genetic background of the SHR/Ola was associated with decreased insulin and glucose concentrations and ameliorated insulin resistance at the tissue level. These findings suggest that closely linked genes on Chr 19, or perhaps even a single gene with pleiotropic effects, influence the clustering of metabolic disturbances in the SHR-BN model.


Diagnostic considerations in virilization: iodomethyl-norcholesterol scanning in the localization of androgen secreting tumors.
Accurate localization of the source of androgen hypersecretion is critical to the appropriate surgical or medical management of women with virilization. Seven patients with virilization and hyperandrogenism of various causes were evaluated with the use of sequential studies: testosterone stimulation and suppression tests; computerized tomography (CT); selective venous catheterization; and 131I-iodomethyl-norcholesterol (NP-59) scintigraphy. Comparison of the diagnostic accuracies of these localization studies with the ultimate diagnoses in this group of virilized women showed that: endocrinologic suppression/stimulation studies are of limited value in tumor localization and helpful only in patients with steroidogenic enzyme deficiencies; both selective catheterization and CT scanning may provide spurious localization data; and NP-59 scintigraphy, by depicting both the anatomic localization and functional androgen hypersecretion, may provide the most significant localization data in the evaluation of patients with virilizing syndromes.


Factors Influencing Adolescent Generalized Anxiety Disorder: A Zero-Inflated Negative Binomial Regression Model.
The current study used secondary data from the 17th Korea Youth Risk Behavior Survey conducted in 2021 to identify risk factors influencing the frequency with which adolescents in Korea experience generalized anxiety. Participants were 54,848 adolescents. Risk factors for generalized anxiety were analyzed using a zero-inflated negative binomial regression model. Of participants, 23.7% reported no generalized anxiety experiences. Risk factors identified in the count model were being female and having low household economic status as well as perceived stress, sadness, subjective sleep insufficiency, and loneliness. In the logit model, being female, in middle school, having middle and low household economic status, not living with family, having perceived stress, sadness, suicidal ideation, subjective sleep insufficiency, loneliness, and body image distortion were significant predictors of future anxiety among participants without anxiety. These results may be useful for planning nursing interventions to improve and prevent future health problems in adolescents. [Journal of Psychosocial Nursing and Mental Health Services, xx(x), xx-xx.].


Being ostensive (reply to commentaries on "Expression unleashed").
One of our main goals with "Expression unleashed" was to highlight the distinctive, ostensive nature of human communication, and the many roles that ostension can play in human behavior and society. The commentaries we received forced us to be more precise about several aspects of this thesis. At the same time, no commentary challenged the central idea that the manifest diversity of human expression is underpinned by a common cognitive unity. Our reply is organized around six issues: (1) languages and their cultural evolution; (2) the pervasiveness of expression in human behavior; (3) artificial intelligence and ostensive communication; (4) communication in other animals; (5) the ecology and evolution of ostensive communication; and (6) biolinguistics and pragmatics.


Aspirin use is associated with improvement in distant metastases outcome in patients with residual disease after neoadjuvant chemotherapy.
Aspirin (ASA) use has been correlated with improved outcomes in high-risk patients at risk for distant metastases. Breast cancer (BC) patients with residual disease, particularly nodal disease (ypN +) after neoadjuvant chemotherapy (NAC), are high-risk patients portending worse outcomes. We hypothesized that ASA use can reduce distant metastases and improve outcomes in these patients. Patients at our institutions from 2005 to 2018, with BC who did not achieve complete response (pCR) after NAC were reviewed (IRB protocol STU- 052012-019). Data, including evidence of ASA use, and clinico-pathologic parameters were analyzed. Survival outcomes were obtained (Kaplan Meier analysis) and univariate (UVA) and multivariable (MVA) Cox proportional hazards regression analyses were performed. 637 did not achieve pCR (ypN+ = 422). 138 were ASA users. Median follow-up for the control and ASA group were 3.8 (IQR 2.2-6.3) and 3.8 (IQR 2.5-6.4) years, respectively. Majority were stage II/III. 387 were hormone receptor positive, 191 HER2 +, and 157 triple negative. On UVA, ASA use, PR status, pathologic and clinical stage showed significance for DMFS, and disease-free survival (DFS). On MVA, ASA use associated with improved 5-year DFS (p = .01, 87.0% vs 79.6%, adjusted HR = 0.48) and improved 5-year DMFS (p = .04, 92.8% vs 89.2%, adjusted HR = 0.57). In the ypN + patients, ASA use associated with improved 5-year DMFS (p = .008, 85.7% vs 70.7%, adjusted HR = 0.43) and DFS (p = .02, 86.8% vs 74.3%, adjusted HR = 0.48). For non-responders, particularly ypN + patients, ASA use associated with improved outcome. These hypotheses-generating results suggest for development of prospective clinical trials of augmented ASA use in selected very high-risk BC patients.


Robotic approach mitigates the effect of major complications on survival after pancreaticoduodenectomy for periampullary cancer.
Major complications (MCs) after pancreaticoduodenectomy (PD) are a known independent predictor of worse oncologic outcomes. There are limited data on the effect of major complications on long-term outcomes after robotic PD (RPD). The aim of this study is to compare the effect of MC on overall (OS) and disease-free survival (DFS) after RPD and open PD (OPD). This is a single-center, retrospective review of a prospectively maintained database of all patients undergoing PD for periampullary cancer including ampullary adenocarcinoma, distal cholangiocarcinoma, and duodenal carcinoma. Univariate analysis was performed on all clinical, pathologic, and treatment factors. MCs were defined as Clavien-Dindo ≥ grade 3. Kaplan-Maier survival analysis was performed with log-rank test for group comparison. Multivariable Cox regression analysis was used to identify factors associated with overall survival (OS) in both the OPD and RPD groups. A total of 190 patients with ampullary carcinoma (n = 98), cholangiocarcinoma (n = 55), and duodenal adenocarcinoma (n = 37) were examined over the study period with 61.1% (n = 116) undergoing RPD and 38.9% (n = 74) undergoing OPD. There was no significant difference in patient demographics between the RPD and OPD cohorts. Furthermore, R0 resection rates, tumor size, and lymph node involvement were similar between the RPD and OPD cohorts. OPD had higher rate of MC (40.5% vs 28.3% in RPD, p = 0.011) including clinically relevant pancreatic fistula (25.7% vs 8.6%, p = 0.001) and wound infection (34.5% vs 13.8%, p < 0.001). MCs were associated with a lower OS in the OPD cohort (HR = 2.18, 95%CI 1.0-4.55, p = 0.038). MCs were not associated with OS in the RPD cohort (HR = 1.55, 95%CI 0.87-2.76, p = 0.14). MCs are associated with worse patient outcomes after OPD but not after RPD. Robotic approach mitigates and possibly abrogates the negative effects of MCs on patient outcomes after PD for malignancy and is associated with improved adjuvant chemotherapy completion rates.


Unemployment among patients with newly diagnosed first-episode psychosis: prevalence and clinical correlates in a U.S. sample.
Although it is well established that people with schizophrenia have markedly high rates of unemployment, less is known about the prevalence and clinical correlates of unemployment in patients newly diagnosed with first-episode psychosis. This analysis documented the prevalence of unemployment and examined previously reported clinical correlates of unemployment in patients with first-episode psychosis hospitalized in an urban, public-sector setting in the southeastern US. Participants (n = 181) were assessed as part of an overarching study of first-episode psychosis using a variety of standardized research instruments. The rate of unemployment was compared to that documented in the general population according to US census data. Bivariate tests of associations between employment status and a number of variables of interest were followed by a multiple logistic regression model based on a previous study from Dublin, Ireland. Some 65.0% of first-episode patients were unemployed in the month prior to hospital admission, which is substantially higher than the rate of unemployment during the same period in the two counties in which recruitment took place. In bivariate tests, unemployment was associated with younger age, fewer years of educational attainment, lower global functioning scores, and more severe negative symptoms. In the logistic regression model, only age and global functioning were independently significant correlates. The remarkably high rate of unemployment in this young, first-episode sample, and the evidence of associations between unemployment, greater symptomatology, and poorer functioning, argue for further research and development on supported employment programs for such patients.


[Double bronchogenic cyst].
Bronchogenic cysts are rare congenital malformations of the tracheobronchial tree and are mostly found in an intrathoracic location. We report a very rare case of a double location - cervical and mediastinal - in a young female patient.


Corporate social marketing: message design to recruit program participants.
To identify variables for a corporate social marketing (SM) health message based on the 4 Ps of SM in order to recruit future participants to an existing national, commercial, self-administered weight-loss program. A systematically evaluated, author-developed, 310-response survey was administered to a random sample of 270 respondents. A previously established research plan was used to empirically identify the audience segments and the "marketing mix" appropriate for the total sample and each segment. Tangible product, pertaining to the unique program features, should be emphasized rather than positive core product and outcome expectation related to use of the program.


Transmission of hepatitis E virus by water: An issue still pending in industrialized countries.
Hepatitis E virus (HEV) is an enteric virus divided into eight genotypes. Genotype 1 (G1) and G2 are specific to humans; G3, G4 and G7 are zoonotic genotypes infecting humans and animals. Transmission to humans through water has been demonstrated for G1 and G2, mainly in developing countries, but is only suspected for the zoonotic genotypes. Thus, the water-related HEV hazard may be due to human and animal faeces. The high HEV genetic variability allows considering the presence in wastewater of not only different genotypes, but also quasispecies adding even greater diversity. Moreover, recent studies have demonstrated that HEV particles may be either quasi-enveloped or non-enveloped, potentially implying differential viral behaviours in the environment. The presence of HEV has been demonstrated at the different stages of the water cycle all over the world, especially for HEV G3 in Europe and the USA. Concerning HEV survival in water, the virus does not have higher resistance to inactivating factors (heat, UV, chlorine, physical removal), compared to viral indicators (MS2 phage) or other highly resistant enteric viruses (Hepatitis A virus). But the studies did not take into account genetic (genogroups, quasispecies) or structural (quasi- or non-enveloped forms) HEV variability. Viral variability could indeed modify HEV persistence in water by influencing its interaction with the environment, its infectivity and its pathogenicity, and subsequently its transmission by water. The cell culture methods used to study HEV survival still have drawbacks (challenging virus cultivation, time consuming, lack of sensitivity). As explained in the present review, the issue of HEV transmission to humans through water is similar to that of other enteric viruses because of their similar or lower survival. HEV transmission to animals through water and how the virus variability affects its survival and transmission remain to be investigated.


Temporal Modulation Detection Depends on Sharpness of Spatial Tuning.
Prior research has shown that in electrical hearing, cochlear implant (CI) users' speech recognition performance is related in part to their ability to detect temporal modulation (i.e., modulation sensitivity). Previous studies have also shown better speech recognition when selectively stimulating sites with good modulation sensitivity rather than all stimulation sites. Site selection based on channel interaction measures, such as those using imaging or psychophysical estimates of spread of neural excitation, has also been shown to improve speech recognition. This led to the question of whether temporal modulation sensitivity and spatial selectivity of neural excitation are two related variables. In the present study, CI users' modulation sensitivity was compared for sites with relatively broad or narrow neural excitation patterns. This was achieved by measuring temporal modulation detection thresholds (MDTs) at stimulation sites that were significantly different in their sharpness of the psychophysical spatial tuning curves (PTCs) and measuring MDTs at the same sites in monopolar (MP) and bipolar (BP) stimulation modes. Nine postlingually deafened subjects implanted with Cochlear Nucleus® device took part in the study. Results showed a significant correlation between the sharpness of PTCs and MDTs, indicating that modulation detection benefits from a more spatially restricted neural activation pattern. There was a significant interaction between stimulation site and mode. That is, using BP stimulation only improved MDTs at stimulation sites with broad PTCs but had no effect or sometimes a detrimental effect on MDTs at stimulation sites with sharp PTCs. This interaction could suggest that a criterion number of nerve fibers is needed to achieve optimal temporal resolution, and, to achieve optimized speech recognition outcomes, individualized selection of site-specific current focusing strategies may be necessary. These results also suggest that the removal of stimulation sites measured with poor MDTs might improve both temporal and spectral resolution.


Preliminary characterization of the material released to the culture medium by Candida albicans yeast and mycelial cells.
Culture filtrate concentrates were obtained from Candida albicans yeast and mycelial cells grown in the presence of 14C-protein hydrolysate for radioactive labeling of cellular polypeptides. Both growth forms released to the medium minor but significant amounts of proteinaceous materials. The analysis of culture filtrate concentrates by means of SDS-polyacrylamide gel electrophoresis and fluorography revealed a similar and complex electrophoretic pattern, though some qualitative and quantitative differences between samples obtained from yeast and mycelial cells were observed. Materials released, mostly composed of mannoproteins as shown by their affinity towards concanavalin A, presented (i) cross-reactivity (by Western immunoblotting and ELISA) against polyclonal antisera to genuine cell wall components (among them the 58-kilodalton fibrinogen-binding mannoprotein) and (ii) high affinity for polystyrene-latex microbeads. Results presented suggest a possible common identity for the molecules shed to the medium and the cell wall protein and mannoprotein constituents.


Effectiveness of interventions involving social networks for self-management and quality of life in adults with diabetes: a systematic review protocol.
The purpose of this systematic review is to explore the effect of interventions involving social networks on self-management and quality of life in adults with diabetes. There is growing evidence that interventions involving social networks have a positive impact on people with diabetes through social support and social participation. However, the existing literature or protocols relate to only one type of diabetes, a certain population, or one type of intervention involving social networks. This study will comprehensively assess the impact of interventions involving social networks on self-management and quality of life for all types of diabetes. This study will consider studies that compare interventions involving the social networks (families, friends and peers) of adults with all types of diabetes with interventions that do not involve social networks. We plan to collect relevant randomized and non-randomized controlled trials for systematic evaluation and meta-analysis by searching PubMed, Embase, Web of Science, CINAHL Complete, Cochrane Central Register of Controlled Trials, ProQuest Dissertations and Theses, and Google Scholar. Studies published in English from database inception to the present will be included. After the search, two researchers will independently screen the literature according to inclusion and exclusion criteria, evaluate the selected literature critically and extract the relevant data required, then meta-analysis will be performed using Joanna Briggs Institute System for the Unified Management, Assessment and Review of Information. PROSPERO CRD42019135949.