Association of decreased T-cell-mediated natural cytotoxicity and interferon production in Down's syndrome.
Total peripheral blood lymphocytes (PBL) and isolated subpopulations from children with Down's Syndrome (DS) and age-matched healthy controls were investigated for their (1) natural killer (NK) and antibody-dependent cellular cytotoxic activities, (2) interleukin 2 (IL-2)-induced augmentation of NK activity, (3) lectin-dependent cellular cytotoxicity (LDCC), (4) ability of serum- and culture-derived soluble suppressor factor(s) to inhibit NK activity of normal lymphocytes, and (5) capacity to produce interferon (IFN) against tumor targets in vitro. T lymphocytes from DS patients demonstrated significantly decreased NK activity against K562 target cells compared to controls. DS lymphocytes also demonstrated a significant reduction in LDCC activity and IL-2-induced enhancement of NK activity. Furthermore, the ability of DS lymphocytes to produce IFN in vitro against K562 target cells was also significantly lower than that for normal PBL. Although sera from DS patients showed a significantly greater inhibitory effect on the NK activity of allogeneic normal PBL than normal sera, culture supernates from DS lymphocytes demonstrated suppressive effects comparable to culture supernates from normal PBL. These studies suggest an association between the decreased NK activity of T-cell subpopulations and lower IFN production by PBL from patients with DS.


Golgi and genetic mosaic analyses of visual system mutants in Drosophila melanogaster.
We have used a Golgi staining procedure in Drosophila melanogaster to examine the structure of individual neurons in the visual systems of the Canton-S wild-type strain, of flies expressing mutations at the Glued, rough, glass, and uneven loci, all of which affect the organization of the visual system, and of genetic mosaics involving the Glued and uneven loci. We have found that the structure of the neurons studied in the wild type is quite similar to that reported for other diptera and that the mutants studied evidence a variety of abnormalities in neuronal morphology, each mutant being characterized by a different spectrum of aberrations. The genetic mosaic analysis of the Glued and uneven loci showed that the structure of individual neurons in the optic lobes is profoundly influenced by the genotype of the cells projecting to that region from the compound eye but that the final form attained by a neuron is not solely controlled by that factor.


Post-harvest regulated gene expression and splicing efficiency in storage roots of sugar beet (Beta vulgaris L.).
Sixteen post-harvest upregulated genes from sugar beet comprising five novel sequences were isolated by subtractive cloning. Transcription profiles covering a period of up to 49 days after harvest under controlled storage conditions and in field clamps are reported. Post-harvest induced genes are involved in wound response, pathogen defense, dehydration stress, and detoxification of reactive oxygen species. An early induction of a cationic peroxidase indicates a response to post-harvest damage. Wound response reactions may also involve genes required for cell division such as a regulator of chromatin condensation and a precursor of the growth stimulating peptide phytohormone phytosulfokine-alpha. Surprisingly, also three putative non-protein coding genes were isolated. Two of these genes show intron specific and storage temperature dependent splicing of a precursor mRNA. The temperature dependent splicing of an intron containing sugar beet mRNA is also maintained in transgenic Arabidopsis thaliana. The storage induced genes are integrated into a model that proposes the response to several post-harvest stress conditions. Temperature regulated splicing may be a mechanism to sense seasonal temperature changes.


Immunophenotypic classification of lymphoblastic leukaemia and lymphocytic lymphoma--an experience in the south-western area of the Cape Province of South Africa.
Adequate tumour material was obtained for phenotypic classification using a standard library of monoclonal antibodies from 81 previously untreated patients with acute lymphoblastic leukaemia (ALL), chronic lymphocytic leukaemia (CLL), or lymphocytic lymphoma (LL). Sixty-one individuals were adults and 20 were children of 14 yr or younger. Fifty-eight of the patients (72%) had acute lymphoblastic leukaemia and the remaining 23 (28%) had chronic lymphocytic leukaemia or lymphocytic lymphoma. Considering only the patients with acute lymphoblastic leukaemia (n = 58) the median age was 19 yr (range 3-69 yr): 9% were black, 43% were coloured, 48% were white, and the distribution between adult (n = 38) and paediatric patients (n = 20) was comparable. Complete remission rate in the adults was 58% and in the paediatric group 85%. For the total group (n = 58) median duration of survival was 59 weeks for common, 39 weeks for null, 63 weeks for T-ALL, and 13 weeks for B-ALL subtypes. In both the common and the null groups overall and disease-free survival was superior in the children. In contrast, no difference was evident in the T-ALL group, which was also notable for its high incidence in young coloured males. The 15 patients with CLL and eight with LL were adults and all the cells were phenotypically of B lineage: in view of the small numbers no comments are possible about ethnic differences. A multi-centre collaborative study is needed to define the epidemiology of haematologic malignancy in South Africa, with emphasis on differences among ethnically distinct subpopulations.


A retrospective study of the prevalence and outcomes of syphilis in pregnancy in a 5-year period.
To determine the prevalence of syphilis in pregnancy and to assess the effect of syphilis on maternal and perinatal outcomes. In a retrospective study, data were reviewed for pregnant women who tested positive for syphilis during routine prenatal screening at a center in India between January 2011 and December 2015. Women with both a positive venereal disease research laboratory (VDRL) test and a positive Treponema pallidum hemagglutination assay (TPHA) were considered to have syphilis, and their maternal and fetal outcomes were assessed. Among 51 164 pregnant women who underwent VDRL testing during the study period, 343 women were VDRL-positive (seropositivity rate 0.7%) and 18 were both VDRL- and TPHA-positive and were considered to have syphilis (seropositivity rate <0.1%). Among these 18 women, there were two stillbirths, four preterm births, and five small-for-gestational-age neonates. Although the prevalence of syphilis was low in the study population, women who were affected had adverse perinatal outcomes. Routine screening of all pregnant women for syphilis as early as possible in pregnancy, with appropriate treatment and follow-up of affected women and newborns, should be done to reduce adverse pregnancy outcomes.


Quantification of long-term accumulation of inhaled ultrafine particles via human olfactory-brain pathway due to environmental emissions - a pilot study.
Olfactory pathway as a viable route for brain uptake of environmental pollutants has been hypothesized in past decade. In such a hypothesis, subclinical low-dose exposure and chronic brain accumulation of exogenous airborne agents are critical to define neurodegenerations, however the information is extremely lacking. Advances in granular measurement of air pollutants, real-time personal exposure monitoring and big data analytics have opened-up an unprecedented opportunity to enable researchers conduct longitudinal investigation and potentially link the external environment condition to risks of human developing neurodegenerative diseases in a foreseeable future. Detailed case studies are provided in this work that illustrate the quantification of human brain accumulation of ultrafine particles (UFPs) from exposure, surface deposition, and pathway penetration via the transport route of nasal olfactory in prolonged timespans. The study links the individual components along the olfactory pathway, showcases the available research capacity, and pinpoints the critical areas of research need in environmental, toxicological and epidemiological studies, significant to a joint effort to bring together an interdisciplinary solution to uncover the insight of time course and dose dependency between environmental exposure and risk of developing neurodegenerative diseases in a foreseeable future. It should be noted that current study assumes that nanoparticle penetration along the olfactory pathway is unidirectional and follows the rate observed in the rodent study. Tissue responses in determining the penetration and retention corresponding to size and composition of the inhaled nanoparticles are not considered.


Traditional, complementary and alternative medicine in children constipation: a systematic review.
This review aims to evaluate the efficacy and safety of complementary and alternative medicine methods for constipation in the pediatric population. Medical literature search was performed in several databases for a variety of Traditional, Complementary and Alternative Medicine in childhood constipation. Databases included Web of Science, Scopus, Embase, Cochrane Library, PubMed, ScienceDirect, Google scholar and a number of Persian databases including IranDoc, Magiran and SID. No time limitation was determined. Clinical trials or case series that had evaluated the effectiveness of CAM therapies in functional constipation of 1-18 year old children were included. Papers not in English or Persian language were excluded. Related articles were screened independently by two reviewers according to their titles and abstracts. A data extraction form was filled in for each eligible paper. Quality assessment of eligible documents was also performed. 30 studies were included, comprising 27 clinical trials and 3 case series. Ten documents were on herbal medicine, nine on traditional medicine, ten on manual therapies and one on homeopathy. Except for two herbal and one reflexology interventions, all studies reported positive effects on childhood constipation, with the majority being statistically significant. As the number of studies in each method was limited, we could not perform a meta-analysis. The scarcity of research on the efficacy and safety of different types of complementary and alternative medicine methods in children with constipation necessitates conducting more studies in each field. Graphical abstract.


Morphometric estimation of stromal edema during delayed implantation in the rat.
Morphometric methods were used at the light microscopic level to investigate the appearance of edema in the endometrial stroma of rats during estradiol-induced implantation after an experimental delay. Comparisons between blastocyst-free and blastocyst-containing sites were made at 18, 12, 16 and 24 h after injection of estradiol (h.a.e.). The development of stromal edema during implantation was found to be diphasic. First, during the initial 8--12 h.a.e., a generalized edema developed all along the uterine horns. Later, from 16 h.a.e. onwards, a local edema was present around the blastocysts. The Pontamine Blue Reaction (PBR) became visible between 20 and 24 h.a.e. The results indicate that the blastocyst is recognized by the stroma considerably before the PBR. The appearance of a local edema around the blastocysts before the PBR might be related to a slow increase in vascular permeability and/or to the increased stromal cell synthetic activity that is known to precede the PBR during early implantation.


Hyperthermia-Induced Controlled Local Anesthesia Administration Using Gelatin-Coated Iron-Gold Alloy Nanoparticles.
The lack of optimal methods employing nanoparticles to administer local anesthesia often results in posing severe risks such as non-biocompatibility, in vivo cytotoxicity, and drug overdose to patients. Here, we employed magnetic field-induced hyperthermia to achieve localized anesthesia. We synthesized iron-gold alloy nanoparticles (FeAu Nps), conjugated an anesthetic drug, Lidocaine, and coated the product with gelatin to increase the biocompatibility, resulting in a FeAu@Gelatin-Lidocaine nano-complex formation. The biocompatibility of this drug-nanoparticle conjugate was evaluated in vitro, and its ability to trigger local anesthesia was also evaluated in vivo. Upon exposure to high-frequency induction waves (HFIW), 7.2 ± 2.8 nm sized superparamagnetic nanoparticles generated heat, which dissociated the gelatin coating, thereby triggering Lidocaine release. MTT assay revealed that 82% of cells were viable at 5 mg/mL concentration of Lidocaine, indicating that no significant cytotoxicity was induced. In vivo experiments revealed that unless stimulated with HFIW, Lidocaine was not released from the FeAu@Gelatin-Lidocaine complex. In a proof-of-concept experiment, an intramuscular injection of FeAu@Gelatin-Lidocaine complex was administered to the rat posterior leg, which upon HFIW stimulation triggered an anesthetic effect to the injected muscle. Based on our findings, the FeAu@Gelatin-Lidocaine complex can deliver hyperthermia-induced controlled anesthetic drug release and serve as an ideal candidate for site-specific anesthesia administration.


In vitro permeation of several drugs through the human nail plate: relationship between physicochemical properties and nail permeability of drugs.
The objectives of the present study are to clarify the relationship between the physicochemical properties and the nail permeability of drugs through human nail plates. Homologous p-hydroxybenzoic acid esters were used to investigate the relationship between the octanol/water partition coefficient and the permeability coefficient of several drugs. The nail permeability was found to be independent of the lipophilicity of a penetrating drug. However, the nail permeability of several model drugs was found to markedly decrease as their molecular weights increased. The nail permeability of an ionic drug was found to be significantly lower than that of a non-ionic drug, and the nail permeability of these drugs markedly decreased as their molecular weights increased. The permeation of a model drug, 5-fluorouracil (5-FU), through healthy nail plates was also determined and compared with that through nail plates with fungal infections. The drug permeation through a nail plate decreased with an increase in nail plate thickness. Nail plates with fungal infections exhibited approximately the same 5-FU permeation as healthy nail plates. We suggest that the permeability of a drug is mainly influenced by its molecular weight and permeability through nails with fungal infection can be estimated from data on healthy nail permeability.


Time-Resolved Spectroscopic Study of N,N-Di(4-bromo)nitrenium Ions in Acidic Aqueous Solution.
Nitrenium ions are common reactive intermediates with high activities towards some biological nucleophiles. In this paper, we employed femtosecond transient absorption (fs-TA) and nanosecond transient absorption (ns-TA) as well as nanosecond time-resolved resonance Raman (ns-TR3) spectroscopy and density function theory (DFT) calculations to study the spectroscopic properties of the N(4,4'-dibromodiphenylamino)-2,4,6-trimethylpyridinium BF4- salt (1) in an acidic aqueous solution. Efficient cleavage of the N-N bond (4 ps) to form the N,N-di(4-bromophenyl)nitrenium ion (DN) was also observed in the acidic aqueous solution. As a result, the dication intermediate 4 appears more likely to be produced after abstracting a proton for the nitrenium ion DN in the acid solution first, followed by an electron abstraction to form the radical cation intermediate 3. These new and more extensive time-resolved spectroscopic data will be useful to help to develop an improved understanding of the identity, nature, and properties of nitrenium ions involved in reactions under acidic aqueous conditions.


Novel valve replacement with an extracellular matrix scaffold in an infant with single ventricle physiology.
Valve replacement in children with functionally univentricular hearts remains challenging. The absence of small prostheses, the lack of growth, and the need for anticoagulation limit these procedures. We describe a 1-year follow-up of an extracellular matrix scaffold tube used as systemic atrio-ventricular valve in an infant.


Indolealkylamines in the venom of the scorpion Thorellius intrepidus.
Scorpions are a group of arthropods that strike fear in many people due to their severe medical symptoms, even death, caused by their venomous stings. Even so, not all scorpion species contain harmful venoms against humans but still have valuable bioactive molecules, which could be used in developing new pharmaceutical leads for treating important diseases. This work conducted a comprehensive analysis of the venom from the scorpion Thorellius intrepidus. The venom of T. intrepidus was separated by size exclusion chromatography, and four main fractions were obtained. Fraction IV (FIV) contained small molecules representing over 90% of the total absorbance at 280 nm. Analysis of fraction FIV by RP-HPLC indicated the presence of three main molecules (FIV.1, FIV.2, and FIV.3) with similar UV absorbance spectra profiles. The molecular masses of FIV.1, FIV.2, and FIV.3 were determined, resulting in 175.99, 190.07, and 218.16 Da, respectively. Further confirmation through 1H-NMR and 13C-NMR analyses revealed that these molecules were serotonin, N-methylserotonin, and bufotenidine. These intriguing compounds are speculated to play a pivotal role in self-defense and increasing venom toxicity and could also offer promising biotechnological applications as small bioactive molecules.


Survivability of Lactobacillus plantarum in nutmeg (Myristica fragrans Houtt) flesh extract and its effect on the performance of broiler chicken.
This study aimed to see if increasing the concentration of nutmeg flesh extract in vitro could increase the growth of Lactobacillus plantarum bacteria and if it had any effect on broiler chicken performance. Different concentrations of nutmeg flesh extract (5, 10, 15, and 20/100 ml distilled water) were combined with 10 ml L. plantarum (bacterial concentration 1 × 109 cfu/ml) to produce synbiotics. A total of 250 unsexed Lohmann broiler chickens were reared together from 0 to 7 days of age in the in vivo study. Beginning on day 8, synbiotics nutmeg flesh extract and L. plantarum were added to the ration in amounts of 0.5, 1, 1.5, and 2 ml/kg for T1, T2, T3, and T4, respectively, while no synbiotics were added to the control diet (T0). The levels of nutmeg flesh extract had a significant (p < 0.05) effect on L. plantarum growth. In the survival test against gastric acid, bile salts, and temperature, the addition of nutmeg flesh extract (20/100 ml distilled water) significantly (p < 0.05) maintained the population of L. plantarum. In vivo studies showed that the T1,T2,T3, and T4 groups gained more body weight (p < 0.05) than the T0 group during the rearing period but had no effect (p > 0.05) on the internal organ weight and carcass of broiler chickens. Nutmeg flesh extract could stimulate the growth of L. plantarum bacteria, and using it as a synbiotic could improve broiler chicken performance.


Enhancement of phagocytosis by neurotensin, a newly found biological activity of the neuropeptide.
Specific binding of neurotensin (NT) to mouse peritoneal thioglycollate-elicited macrophages and macrophages differentiated in vitro from bone marrow cells was demonstrated and characterized. NT binding to these phagocytes modulated their phagocytic capacity in a biphasic manner. At concentrations of 10(-14) to 10(-9) M NT, a dose-dependent augmentation of phagocytosis (up to 2-fold) was observed. Further increases in the concentration of NT resulted in a gradual decrease of the augmented response until the basal phagocytic activity (in the absence of NT) was reached. Three partial sequences of NT, NT (8-13), NT (6-13) and NT (1-10), were also effective in augmenting the phagocytic response of thioglycollate elicited macrophages, but the maximal effect was attained at about 10(-7) M and stayed at that level up to a concentration of 10(-5) M. The activity of the three NT partial sequences was comparable to that of substance P and tuftsin. Scatchard analysis of (3H)NT binding to macrophages suggested the existence of two populations of binding sites, a major population of relatively low affinity binding sites and a small population of high affinity binding sites. NT (8-13), NT (6-13), substance P and tuftsin competed with (3H)NT binding to the low affinity sites with a comparable KI to that of NT. NT (1-10) did not compete for the binding at the low affinity sites. It is suggested that NT binding to the high affinity sites leads to enhancement of phagocytosis, whereas its binding to the low affinity sites leads to inhibition of the augmented response. However, the low affinity sites are the sites of interaction of NT (8-13), NT (6-13), substance P and tuftsin with the phagocytes and their saturation with the peptides leads to augmentation of phagocytosis.


Bilateral vocal cord paralysis after anterior cervical discoidectomy and fusion in a case of whiplash cervical spine injury: a case report.
Bilateral vocal cord paralysis is a risk of anterior cervical discoidectomy and fusion. We discuss the mechanism of vocal cord paralysis and the precautions necessary to avoid this catastrophic complication. A rare case of bilateral vocal cord paralysis after anterior cervical discoidectomy and fusion (ACD/F) is reported. The patient, a 37-year-old male, was paraplegic, had bilateral intrinsic hand muscle weakness and sphincter involvement following a whiplash cervical spinal injury. A C5-C6 ACD/F for traumatic C5-C6 disc prolapse was performed. On the third postoperative day, he developed difficulty in coughing and a husky voice. Otolaryngological evaluation revealed bilateral vocal cord paralysis. He later required a tracheostomy that partially alleviated his major symptoms. In patients undergoing ACD/F, a mandatory preoperative evaluation of the vocal cords should be performed. An appropriate modification in surgical planning should be made if vocal cord palsy is diagnosed preoperatively to prevent bilateral vocal cord paralysis. Proper and judicious use of Cloward retractors is advocated.


Two-year effectiveness of erenumab in resistant chronic migraine: a prospective real-world analysis.
Controlled and real-world evidence have demonstrated the efficacy of calcitonin gene related peptide (CGRP) monoclonal antibodies (MABs) in migraine. However, data on the over-one-year sustained effectiveness of CGRP MABs in resistant chronic migraine (CM) is sparse. METHODS: This is a two-year real-world prospective analysis of an ongoing single centre audit conducted in patients with resistant CM. Patients received monthly erenumab for six months before assessing its effectiveness. Responders were considered those who achieved at least 30% reduction in monthly migraine days (MMD) by month 6, compared to baseline. Secondary outcomes were also analysed, including changes of the Headache Impact Test version 6 (HIT-6). One hundred sixty-four patients [135 (82.3%) females; mean age 46 SD 14) years] were included in the audit and 160 patients analysed. Patients had failed a mean of 8.4 preventive treatments at baseline. At month 6, 76 patients (48%) were 30% responders to erenumab, 50 patients (31%) were 50% responders and 25 (15%) were 75% responders. The mean reduction in MMD at month 6 was 7.5 days compared to baseline (P < 0.001). At month 12 and month 18, 61 patients (38%) and 52 patients (33%) remained 30% responders respectively. At month 24, 36 patients (23%) remained 30% responders, 25 patients (16%) and 13 patients (8%) were respectively 50% and 75% responders. Compared to 95% of patients at baseline, at months 6, 12 and 24, 46%, 29% and 16% of responders respectively had severe disability. At least one adverse event at month 6, 12, 18 and 24 was reported by 49%, 19%, 11% and 3% of patients. By month 6, 13% of patients discontinued the treatment because of side effects, often constipation. Long-term sustained effectiveness of erenumab was reported only by a minority of resistant CM patients. Although more research in resistant migraine is needed, Erenumab can provide long-term meaningful reduction in migraine load and migraine-related disability in some patients.


Enhancing KDM5A and TLR activity improves the response to immune checkpoint blockade.
Immune checkpoint blockade (ICB) therapies are now established as first-line treatments for multiple cancers, but many patients do not derive long-term benefit from ICB. Here, we report that increased amounts of histone 3 lysine 4 demethylase KDM5A in tumors markedly improved response to the treatment with the programmed cell death protein 1 (PD-1) antibody in mouse cancer models. In a screen for molecules that increased KDM5A abundance, we identified one (D18) that increased the efficacy of various ICB agents in three murine cancer models when used as a combination therapy. D18 potentiated ICB efficacy through two orthogonal mechanisms: (i) increasing KDM5A abundance, which suppressed expression of the gene PTEN (encoding phosphatase and tensin homolog) and increased programmed cell death ligand 1 abundance through a pathway involving PI3K-AKT-S6K1, and (ii) activating Toll-like receptors 7 and 8 (TLR7/8) signaling pathways. Combination treatment increased T cell activation and expansion, CD103+ tumor-infiltrating dendritic cells, and tumor-associated M1 macrophages, ultimately enhancing the overall recruitment of activated CD8+ T cells to tumors. In patients with melanoma, a high KDM5A gene signature correlated with KDM5A expression and could potentially serve as a marker of response to anti-PD-1 immunotherapy. Furthermore, our results indicated that bifunctional agents that enhance both KDM5A and TLR activity warrant investigation as combination therapies with ICB agents.


Severe toxicity and polymerase-γ gene abnormalities in Malawian adults on stavudine-based antiretroviral therapy.
In a cohort study of Malawian adults who were followed up through their second year of stavudine-containing antiretroviral therapy, we sequenced the polymerase-γ gene (POLG) of 10 of the 14 patients with the most severe stavudine side effects. No mutations were observed, suggesting that monogenic POLG mutations are not a common pathogenic determinant of severe stavudine-associated mitochondrial toxicity in Malawians.


RNA interference-mediated silencing of NANOG reduces cell proliferation and induces G0/G1 cell cycle arrest in breast cancer cells.
Since the processes of normal embryogenesis and neoplasia share many of similar pathways, tumor development has been interpreted as an abnormal form of organogenesis. NANOG is a homeodomain-containing transcription factor that functions to maintain self-renewal and proliferation of embryonic stem cells (ESCs). Aberrant expression of NANOG has been observed in many types of human malignancies. However, its potential implication in tumorigenesis has not been fully clarified. In this study, we have employed small interference RNA (RNAi) technology to silence endogenous NANOG expression in breast cancer cells and successfully selected three independent clones with stably inhibited NANOG expression of MCF-7 cells. Functional analysis revealed that down-regulation of NANOG reduced cell proliferation, colony formation and migration ability of MCF-7 cells. Consistently, proliferation of breast cancer MDA-MB-231 cells was also significantly inhibited after the knockdown of NANOG expression. Interestingly, we found that the expression levels of cyclinD1 and c-myc were markedly down-regulated and the cell cycle were blocked at the G0/G1 phases after the knockdown of NANOG, while the expression of cyclinE and signal transducers and activators of transcription3 (STAT3) remained unaffected. In addition, the expression of NANOG and cyclinD1 can be rescued after the transfection of pcDNA3.1 (-)-NANOG expression vector into the three clones. Finally, our chromatin immunoprecipitation (ChIP) experiment showed that NANOG protein can bind to the promoter region of cyclinD1 and regulate cells cycle. Taken together, our findings may not only establish a molecular basis for the role of NANOG in modulating cell cycle progression of breast cancer cells but also suggest a potential target for the treatment of at least some subtypes of breast cancer.


Vitamin D deficiency and insufficiency after pediatric liver transplantation.
Vitamin D deficiency and insufficiency are increasingly recognized in the general population, including healthy children. There is also an increasing emphasis on the importance of vitamin D status following pediatric liver transplantation and specifically its relationship to metabolic bone disease and growth retardation. Vitamin D insufficiency has also been associated with multiple immunological and metabolic disorders in adults. To our knowledge, this has not been systematically evaluated in children undergoing liver transplantation to date. Between October 2004 and August 2008, serum 25-(OH)-vitamin D levels were measured in 199 children who had undergone liver transplantation at Birmingham Children's Hospital. Potential factors contributing to vitamin D levels were evaluated. Additionally, we evaluated a possible relationship between vitamin D levels and immunological phenomena and metabolic complications. Median 25-(OH)-vitamin D level was 19.5 ng/mL (range: 4.4-71.4 ng/mL). A total of 105 children (53%) had insufficient vitamin D levels and 28 children (14%) showed vitamin D deficiency. The only factors found to be associated with vitamin D deficiency were season of sample, ethnicity, and PTH levels. Vitamin D deficiency was more prevalent during the first year after transplantation. We did not find a significant relationship between vitamin D levels and graft function or any other immunological and metabolic complications. Vitamin D insufficiency and deficiency are common in children after liver transplantation, especially in winter and spring and in non-white patients. Initial post-transplant period and high PTH are significantly associated with vitamin D deficiency. Vitamin D status should be monitored following pediatric liver transplantation and vitamin D supplementation provided as required.


Nanomedicines: An approach to treat placental insufficiency and the current challenges.
Preeclampsia and fetal growth restriction are common pregnancy complications that significantly impact perinatal health and offspring development later in life. The origin of these complex syndromes overlap in placental insufficiency. Progress in developing treatments for maternal, placental or fetal health is mainly limited by the risk of maternal and fetal toxicity. Nanomedicines are a promising approach to safely treat pregnancy complications since they can regulate drug interaction with the placenta to enhance efficacy of the treatment while minimizing exposure of the fetus. This narrative review discusses the current developments and challenges of nanomedicines during pregnancy with a focus on preclinical models of placenta insufficiency syndromes. Firstly, we outline the safety requirements and potential therapeutic maternal and placental targets. Secondly, we review the prenatal therapeutic effects of the nanomedicines that have been tested in experimental models of placental insufficiency syndromes. The majority of liposomes and polymeric drug delivery system show promising results regarding the prevention of trans-placental passage nanomedicines in uncomplicated and complicated pregnancies. The others two studied classes, quantum dots and silicon nanoparticles, have been investigated to a limited extent in placental insufficiency syndromes. Characteristics of the nanoparticles such as charge, size, and timing of administration have been shown to influence the trans-placental passage. The few available preclinical therapeutic studies on placental insufficiency syndromes predominantly show beneficial effects of nanomedicines on both maternal and fetal health, but demonstrate contradicting results on placental health. Interpretation of results in this field is complicated by the fact that results are influenced by the choice of animal species and model, gestational age, placental maturity and integrity, and nanoparticle administration route. Nanomedicines form a promising therapeutic approach during (complicated) pregnancies mainly by reducing fetal toxicity and regulating drug interaction with the placenta. Different nanomedicines have been proven to effectively prevent trans-placental passage of encapsulated agents. This can be expected to dramatically reduce risks for fetal adverse effects. Furthermore, a number of these nanomedicines positively impacted maternal and fetal health in animal models for placental insufficiency. Demonstrating that effective drug concentrations can be reached in the target tissue. While these first animal studies are encouraging, more research is needed to better understand the influence of the pathophysiology of this multi-factorial disease before implementation in clinical practice can be considered. Therefore, extensive evaluation of safety and efficacy of these targeted nanoparticles is needed within multiple animal, in vitro, and/or ex vivo models. This may be complemented by diagnostic tools to assess the disease status to identify the best time to initiate treatment. Together these investigations should contribute to building confidence in the safety of nanomedicines for treating mother and child, as safety has, understandably, the highest priority in this sensitive patient groups.


Correlation between suspended particles in the environmental air and causes of disease among inhabitants: cross-sectional studies using the vital statistics and air pollution data in Japan.
To identify the diseases that correlate with suspended particle concentration in the ambient air, a cross-sectional epidemiological study was conducted using the annual vital statistics and air pollution estimates of 1881 points throughout Japan. The concentration of suspended particulate matters (SPMs) 10 microm or less in diameter were hypothetically converted to PM(2.5) values (converted PM(2.5) or cPM(2.5)) by using a conversion factor obtained from 25 estimates in Japan. Among various causes of death, a significant correlation was observed between both the SPM and cPM(2.5) (SPM/cPM(2.5)) levels and the age-adjusted death rates of ischemic heart disease or hypertensive heart disease in both genders. Correlation was noted with pneumonia, asthma, chronic bronchitis/emphysema, or lung cancer only in females. Unexpectedly, breast, endometrial, and ovarian cancer also showed significant increases in mortality rates related to the SPM/cPM(2.5) level, suggesting a role for suspended particles in the ambient air with or without gaseous component as a possible endocrine-disrupting, estrogenic agent. Multivariate regression analysis of confounding factors, smoking rate, population density, and hormone-related factors revealed consistent significance of SPM/cPM(2.5) in these diseases.


Detection of shrew-borne hantavirus in Eurasian pygmy shrew (Sorex minutus) in Central Europe.
Recently, it was found that not only rodents but also shrews are reservoir hosts of hantaviruses. In Central Europe, only Seewis virus, associated with the Eurasian common shrew (Sorex araneus), has been recognized until now. In the present report, tissue samples from shrews belonging to Crocidurinae and Soricinae subfamilies, trapped in Czech Republic, Germany, and Slovakia, were screened for the presence of novel hantaviruses. Three new hantavirus partial L-segment sequences were obtained from pygmy shrews (Sorex minutus) trapped in Czech Republic and Germany. Complete nucleocapsid protein- and glycoprotein precursor-coding S- and M-segment sequences were then determined for the newly recognized hantavirus strains, CZ/Beskydy/412/2010/Sm, CZ/Drahany/420/2010/Sm, and DE/Dürrbach/1912/2009/Sm. Phylogenetic analyses showed that they represent strains of Asikkala virus (ASIV), a novel hantavirus also found in pygmy shrews from Finland. Our study reveals a broad geographic distribution of ASIV across Europe and indicates pygmy shrew as the primary reservoir host. Future studies will have to determine the pathogenic relevance of ASIV.


Healing of Bone Affections and Gangrene with Low-Intensity Laser Irradiation in Diabetic Patients Suffering from Foot Infections.
OBJECTIVE: Evalution of low-intensity laser irradiation on the healing of bone affections and gangrene in patients suffering from diabetic microangiopathy. DESIGN: Case-report study. PATIENTS: Two consecutive diabetic male patients with gangrene, osteomyelitis, and bone fractures. INTERVENTION: Helium-neon laser irradiation (36 J/cm2 ) 50 min/day. MAIN OUTCOME PARAMETER: Healing of gangrene and corticalis lesion as well as remineralisation of bone affections. RESULTS: Within a mean period of 14 weeks not only a complete healing of the diabetic gangrenes but also a radiographically determined reestablishment of corticalis and remineralisation of preexisting bone affections could be achieved. CONCLUSION: We therefore conclude that low-intensity laser irradiation should be further tested as an additional beneficial therapeutic modality for the healing of gangrene and bone affections in diabetic patients.


[Medial sural artery perforator fasciocutaneous flap for the reconstruction of tongue and mouth base].
Despite the well-known high donor site morbidity of the radial forarm flap, it has still remained the first option for the reconstruction of the tongue and the floor of mouth. However, a desire for an alternative, thin fasciocutaneous flap has led to the use of the median sural artery perforator flap. Three patients had reconstructive surgery used MSAP flaps, after radical tumor excision. The flap was based in all cases on a dominant perforator vessel. The size of the skin paddles ranged between 20-32 cm2, and the length of the vascular pedicle between 8.2-11 cm. The mean thickness of the flap was 6.5 mm. MSAP flap is an ideal solution for surgical reconstruction in the oral cavity.


Observations on template switching during DNA replication through long inverted repeats.
The bacterial Tn5 transposon consists of a pair of long inverted repeats flanking a central region that carries genes for antibiotic resistance. An analysis of DNA replication through Tn5 by two-dimensional gel electrophoresis has revealed two interesting features: (i) a spike representing X-shaped molecules, and (ii) a spot representing a barrier on the arc of Y-shaped replication intermediates. The electrophoretic behavior of various restriction fragments derived from this region indicates that the X molecules contain two linear Tn5 fragments joined together by a cross connection (Holliday junction). However, their formation is recA independent. The junction seems to connect the right inverted repeat of one fragment to the left inverted repeat of the other. The structure of the X molecules suggests that they could be formed by template switching when synthesis of the leading strand enters the right inverted repeat. One possible mechanism is that switching occurs at the center of a transient cruciform structure. A similar switching event, occurring when synthesis of the leading strand enters the left inverted repeat, could give rise to the barrier. These results imply that the inviability of palindromic DNA, which has previously been attributed to the slowing down of replication, may actually be caused by frequent template switching.


Predicting outcome in pediatric submersion victims.
To predict outcome in children after near-drowning. Retrospective cohort study. Vegetative state and death were classified as unfavorable outcomes, whereas all other outcomes were classified as favorable. Demographic, episode-related, clinical, laboratory, and treatment variables available at the time of admission were evaluated for their usefulness in predicting outcome. Pediatric referral hospital. Children admitted after submersion injury in non-icy waters. The study cohort comprised 194 children (median age, 2.6 years; range, 5 months to 18 years); 131 were neurologically normal at the time of discharge, 10 had some degree of neurologic impairment, 15 were in a vegetative state at the time of discharge, and 38 died. We used a combination of partitioning and logistic regression to combine variables in a prediction rule that was always correct when unfavorable outcome was predicted. The final rule predicted favorable outcome for all children who were not comatose. Among comatose children, unfavorable outcome was predicted by a combination of absent pupillary light reflex, increased initial blood glucose concentration, and male sex. This rule had a specificity of 100%--children with favorable outcomes were always predicted to do well--and a sensitivity of 65%. Therefore the rule was overly optimistic for 35% of patients with unfavorable outcomes. Pediatric submersion victims can be assigned to high or low likelihoods of unfavorable outcome with the use of four variables: comatose state, lack of pupillary light reflex, sex, and initial blood glucose concentration. This prediction rule may be useful if it can be validated in another cohort.


Correction of a Secondary Bilateral Cleft Lip Nasal Deformity in Adults Using Repositioning of Both Lower Lateral Cartilages and Nasal Tip Plasty Through an Open Bilateral Reverse-U Incision.
Correcting a secondary bilateral cleft lip nasal deformity is very complex with many challenges due to its complexity. This study presents the surgical results after correcting a secondary bilateral cleft lip nasal deformity using isolation and repositioning of the lower lateral cartilages, the columellar strut, and an onlay graft on the nasal tip. Eighteen patients who had bilateral cleft lip nasal deformities and who had surgery performed between September 2013 and December 2019 were included in this study. The age of the patients ranged between 19 and 52 years. Open rhinoplasty with bilateral reverse-U incision was performed. The lower lateral cartilages were isolated and repositioned. Nasal tip support is provided using a columellar strut with a septal cartilage or Medpor strut. In the vertical component of the nasal tip, a conchal cartilage graft was used. The mean follow-up period was 2 years (ranging from 1 to 6 years). Fourteen of the 18 patients underwent photogrammetric evaluation. After surgery, the projection of the nasal tip and angle increased, but nasal bridge length decreased. The columella-labial angle significantly increased by 10.1% after surgery which was statistically significant (P < 0.05). The angle between the nostril axes significantly decreased by 46.2% postoperatively and also reached statistical significance (P < 0.05), indicating that the displaced alar base and lower nostril sill improved and the major axis of the nostril changed more vertically oblique. All patients were pleased with their surgical results. The proposed technique was highly effective in correcting secondary bilateral cleft lip nasal deformities in adults.


Analysis of collagen isotypes in crystalloid structures of salivary gland tumors.
Extracellular collagenous crystalloids (CCs) have been reported in salivary gland tumors. To study the occurrence and characteristics of these structures we reviewed 230 pleomorphic adenomas and myoepitheliomas of both major and minor salivary glands. Twelve of these cases contained crystalloids composed of radially arranged collagen fibers. However, no CCs were found in 124 malignant salivary gland tumors of different types. We show that CCs contain types I and III collagen but not type II, IV, or VI collagen. Moreover, cells surrounding CCs expressed the basement membrane molecules laminin and type IV collagen. These cells also showed other immunohistochemical features typical of myoepithelial cells.


Endobronchial ultrasound: a pictorial essay.
endobronchial ultrasound has gained widespread popularity in the last decade, becoming the primary technique for minimally invasive evaluation of the mediastinum and staging of lung cancer. Several tertiary and quaternary care institutes use this method, performed by trained and accredited specialists. Its main indications are (I) diagnosis and staging of lung cancer, (II) mediastinal lymphadenopathy diagnosis (III) sampling peripheral pulmonary lesions. this manuscript aims to describe the operational potential of both convex endobronchial ultrasound probe and radial endobronchial ultrasound probe technology, focusing on lung cancer. This narrative review is complemented with by the description of peculiar clinical cases in which endobronchial ultrasound played a pivotal role in reaching the diagnosis.


The effectiveness of nutrition counselling by Australian General Practitioners.
To determine whether General Practitioners (GPs) consider or provide nutrition counselling for hypertension, diabetes, lipid disorders, ischaemic heart disease (IHD), overweight or obesity, and whether GPs include assessment of the patient's usual diet, assessment of the patient's readiness to change their diet, provision and discussion of nutrition leaflets when counselling. A self-completed questionnaire. New South Wales, Australia. A total of 399 GPs were surveyed using a division mailing list. Questionnaires were distributed in May 2004 with two reminders provided at four-weekly intervals. Of the 399 GPs, 28 no longer practiced at the address while nine were on extended leave. Of the remaining 362, 50% responded, 5% declining to participate, while 163 (45%) completed the questionnaire. GPs were less likely to strongly agree to consider nutrition for hypertension (37%), IHD (61%) and overweight (68%), than diabetes (86%), lipid disorders (82%) and obesity (83%). They were also less likely to strongly agree to provide nutrition for hypertension (22%), IHD (46%) and overweight (45%), than diabetes (79%), lipid disorders (71%) and obesity (68%). In total, 97% of GPs provided some nutrition counselling, with 66% 'often' assessing the patients diet and 59% 'often' assessing the patient's readiness to change their diet. In total, 45% were unaware of stage of change behaviour theory. A total of 85% used nutrition leaflets and 59% 'often' discussed these with their patients. Determining what are the barriers to nutrition counselling for hypertension, IHD and overweight is urgently needed. Educating GPs on stage of change behaviour theory could increase the efficacy of the counselling provided.


Differential radiosensitizing potential of temozolomide in MGMT promoter methylated glioblastoma multiforme cell lines.
To investigate the radiosensitizing potential of temozolomide (TMZ) for human glioblastoma multiforme (GBM) cell lines using single-dose and fractionated gamma-irradiation. Three genetically characterized human GBM cell lines (AMC-3046, VU-109, and VU-122) were exposed to various single (0-6 Gy) and daily fractionated doses (2 Gy per fraction) of gamma-irradiation. Repeated TMZ doses were given before and concurrent with irradiation treatment. Immediately plated clonogenic cell-survival curves were determined for both the single-dose and the fractionated irradiation experiments. To establish the net effect of clonogenic cell survival and cell proliferation, growth curves were determined, expressed as the number of surviving cells. All three cell lines showed MGMT promoter methylation, lacked MGMT protein expression, and were sensitive to TMZ. The isotoxic TMZ concentrations used were in a clinically feasible range of 10 micromol/L (AMC-3046), 3 micromol/L (VU-109), and 2.5 micromol/L (VU-122). Temozolomide was able to radiosensitize two cell lines (AMC 3046 and VU-122) using single-dose irradiation. A reduction in the number of surviving cells after treatment with the combination of TMZ and fractionated irradiation was seen in all three cell lines, but only AMC 3046 showed a radiosensitizing effect. This study on TMZ-sensitive GBM cell lines shows that TMZ can act as a radiosensitizer and is at least additive to gamma-irradiation. Enhancement of the radiation response by TMZ seems to be independent of the epigenetically silenced MGMT gene.


[Risk factors for contact lens-related microbial keratitis: A multicenter case-control study].
Currently, the most feared complication by ophthalmologists of contact lens (CL) wear is microbial keratitis (MK), even though its incidence remains low. It is also a significant financial burden for society. This study aimed to identify the risk factors for CL-related MK especially with regard to hygiene and pattern of use, in a large, prospective, multicenter, case-control study. A multicenter retrospective case-control study was designed. The CL-related MK subpopulation (case) was compared with healthy CL wearers (control) using a 52-item anonymous questionnaire designed to determine subject demographics, lens wear history, lens type and disinfection solution, fitting, patient education, hygiene and maintenance of contact lenses, and patient history. Univariate logistic regression analysis was performed to compare both groups. The study included 497 cases and 364 controls. The risk factors associated with the greatest increased odds of CL-related MK were as follows: extended wear (OR=2.96 [1.65-5.33], P<0.001), occasional overnight lens use (OR=6.37 [4,55-8.90], P<0.001), fitting by an optician (OR=1.97 [1.38-2.83], P<0.001), absence of ophthalmologic exam (OR=6.56 [2-22], P<0.01) or no training in handling the contact lens (OR=4.47 [2.27-8.77], P<0.01), use of optician's disinfection solution (OR=5.55 [3.12-9.85], P<0.001), mixing solutions ("topping off") (OR=4.68 [2.73-8.04], P<0.001), no case replacement (OR=3.95 [2.28-6.82] P<0.01), no compliance with hygiene rules and smoking (OR=2.29 [1.67-3.14], P<0.01). The protective factors associated with the greatest reduction in OR were female gender (OR=0.49 [0.36-0.66], P<0.01), hypermetropia (OR=0.28 [0.16-0.48], P=0.01), rigid contact lens wear, fitting by an ophthalmologist, written and verbal instruction, and daily case maintenance. The knowledge of these risks factors incentivizes action at all levels to reduce the incidence of MK, from the prescriber to the patient, including the type of CL, case and contact lens solution.


Cell type-specific NRBF2 orchestrates autophagic flux and adult hippocampal neurogenesis in chronic stress-induced depression.
Dysfunctional autophagy and impairment of adult hippocampal neurogenesis (AHN) each contribute to the pathogenesis of major depressive disorder (MDD). However, whether dysfunctional autophagy is linked to aberrant AHN underlying MDD remains unclear. Here we demonstrate that the expression of nuclear receptor binding factor 2 (NRBF2), a component of autophagy-associated PIK3C3/VPS34-containing phosphatidylinositol 3-kinase complex, is attenuated in the dentate gyrus (DG) under chronic stress. NRBF2 deficiency inhibits the activity of the VPS34 complex and impairs autophagic flux in adult neural stem cells (aNSCs). Moreover, loss of NRBF2 disrupts the neurogenesis-related protein network and causes exhaustion of aNSC pool, leading to the depression-like phenotype. Strikingly, overexpressing NRBF2 in aNSCs of the DG is sufficient to rescue impaired AHN and depression-like phenotype of mice. Our findings reveal a significant role of NRBF2-dependent autophagy in preventing chronic stress-induced AHN impairment and suggest the therapeutic potential of targeting NRBF2 in MDD treatment.


Money and mental disorder: toward behavioral cost accounting for primary prevention.
This paper reviews recent retrospective sociological research suggesting that rises as well as falls in the economy are associated with such indicators of mental disorder as suicide and mental hospitalization. The review emphasizes that a lag exists between economic change and the changes in associated mental indicators. It is suggested that these findings hold promise both for early warning for practitioners and for primary prevention. Also described is a survey in four centers of 93 community mental health workers, indicating that such workers are receptive to the use of such economic indicators but not well-informed about them. Suggestions are made for prospective research to relate economic change to mental disorder through such intervening constructs as life change and stress. Such research, it is hoped, would expand the capacities of community psychologists to account for the behavioral costs of economic policy alternatives.


High GRP78 levels in Covid-19 infection: A case-control study.
Covid-19 infection was declared a global pandemic by WHO on March 11, 2020. GRP78 protein is known to be involved in the intrusion of numerous viruses. Our current study tries to provide some insight into the variation of GRP78 protein levels in patients with Covid-19 (-) pneumonia, Covid-19 (+) pneumonia, and CT negative Covid-19 infection in comparison to the normal population through a larger number of cases. 42 patients who have Covid-19 (-) pneumonia; 72 patients who have Covid-19 infection (30 pneumonia,42 CT negative patients) and 30 patient who have no known diseases (control group) have included in the study after the clinical and radiological evaluation. Serum GRP78 levels of the subjects were measured through a commercially available enzyme-linked immunosorbent assay (ELISA) kit. The GRP78 level was found to be significantly higher in the Covid-19 infection group than both Covid-19 (-) pneumonia and control group (p = 0.031 and p = 0.0001, respectively).No significant difference was evident between Covid-19 (-) pneumonia, Covid-19 (+) pneumonia and CT negative Covid 19 infection groups with respect to GRP78 levels (p = 0.09). In addition, the GRP78 levels were significantly higher in the Covid-19 (-) pneumonia group than the control group (p = 0.0001). This prospective case-control study reveals that the serum GRP78 levels significantly increased during Covid-19 infection in comparison to both the Covid-19 (-) pneumonia and the control group. As the association between SARS-CoV-2 virus and GRP78 protein is revealed more clearly, this association may come to the fore as a therapeutic target.


Gonococcal infections of penile prostheses.
The first two known cases of Neisseria gonorrhoeae infection of a penile implant are reported. The literature regarding periprosthetic infections is reviewed, and the mode of transmission of the gonococcal organism to the corpora is discussed.


Early Diagnosis of Typhoid By PCR For FliC-d Gene of Salmonella Typhi in Patients Taking Antibiotics.
To compare PCR (Polymerase Chain Reaction) with blood culture, typhi-dot and Widal test for the diagnosis of typhoid in patients taking antibiotics. Cross-sectional, comparative study. National University of Sciences and Technology, Islamabad, Pakistan, from April 2013 to August 2014. One hundred and five patients were included in the study. Blood was collected and inoculated into tryptone soya broth for culture. Any growth obtained was identified by API 20 E and confirmed by Salmonella anti-sera. Typhi-dot and Widal test were also done on all the samples. DNA extraction was done and PCR was carried out. Among the 105 patients, 79 (75.2%) were males and 26 (24.8%) were females, with mean age of 20.64 ±14 years. Typhi-dot was positive in 58 (55.2%) and negative in 47 (44.8%) patients. Blood widal test was positive in 27 (25.7%) and negative in 78 (74.3%) patients. Salmonella Typhi was positive on blood culture in only one (1%) patient. PCR for Salmonella Typhi was positive in 102 (97.1%) and negative in 3 (2.9%) patients. Positive cases detected by PCR were significantly higher as compared to Typhi-dot (p < 0.001), blood Widal test (p < 0.001) and blood culture (p < 0.001). Positivity rate of PCR was significantly higher as compared to blood culture, Typhi-dot or Widal test for diagnosing typhoid in patients who were already taking antibiotics.


Ballistic diaphyseal forearm fractures result in high incidence of neurovascular injury and compartment syndrome but have low rates of early infection: A single level I trauma center experience.
Ballistic injuries to the upper extremity represent a small subset of injuries, and there is little data to provide guidance on management and outcomes. The purpose of this study is to assess the incidence of neurovascular injuries, compartment syndrome, and early postoperative infection, as well as patient and injury factors predictive of neurovascular injury following ballistic fractures of the forearm. A retrospective review of operatively treated ballistic forearm fractures at a single level I trauma center between 2010 and 2022 was performed. Thirty-three patients with 36 forearm fractures were identified. Only diaphyseal injuries in patients greater than 18 years old were included. Medical and radiographic records were reviewed to identify pre-injury patient-specific factors, including age, sex, smoking status, and history of diabetes. Injury characteristics, including the type of firearm used, forearm fracture location, and any associated neurologic or vascular injury, as well as compartment syndrome, were collected and analyzed. Short-term outcomes such as post-operative infection and recovery of neurologic function were also collected and analyzed. The median age was 27 years (range: 18-62), with a majority of male patients (78.8%, n = 26). 4 patients (12.1%) sustained high-energy injuries. 4 patients (12.1%) were found to have compartment syndrome pre-operatively or intra-operatively. 11 patients (33.3%) had nerve palsies postoperatively with 8 patients (24.2%) continuing to have nerve palsies at their final follow-up (mean follow-up= 149.9 +/- 187.2 days). The median length of stay was 4 days. There were no patients with infection at follow-up. Ballistic forearm fractures are complex injuries and can result in severe complications such as neurovascular injury and compartment syndrome. As such, a comprehensive evaluation and appropriate management of ballistic forearm fractures are essential to minimize the risk of severe complications and optimize patient outcomes. In our experience, when treated operatively, these injuries have a low rate of infection.


The Effect of MIpaste Plus and Reminpro on Incipient Caries Using DIAGNOdent and SEM: An Invitro Study.
The remineralization of early caries lesion has an effective role on decreasing caries. For initial remineralization of caries lesion, using Compounds of Casein phosphopeptides (CPP) in different studies has been proposed. REMINPRO including Fluoride, Xylitol and Calcium phosphate has just been offered in the market. This study aims to investigate the efficacy of Reminpro and MI paste plus in terms of remineralization of early enamel lesions. In 15 samples of healthy enamels of the maxillary first premolar teeth and 15 samples of Primary Mandibular First Molar under the effect of demineralized gel, artificial caries has been created. The samples have been divided in 3 groups of 20. After performing the cycles of demineralization and remineralization during 5 weeks, the samples were investigated by DIAGNOdent and two samples from each group were compared with SEM. To investigate the remineralization of enamel, two-way ANOVA and to compare the groups in pair, the post hoc tests were used. The mean of mineralization of teeth in the group using reminpro was 25.2 ± 6.16 and in the group using MI paste plus was 23 ± 5.60, which was significantly high. MI paste plus in mineralization of initial enamel caries were more efficient that reminpro pate.


Event-related potentials in patients with temporal lobe epilepsy reveal topography specific lateralization in relation to the side of the epileptic focus.
Event-related potentials (ERPs) were recorded during a continuous recognition memory paradigm in patients with left-sided (LTLE; n = 8) or right-sided temporal lobe epilepsy (RTLE; n = 6), and in healthy control subjects (n = 24). Control subjects and both patient groups exhibited consistent OLD/NEW ERP-differences from 200-600 ms after stimulus onset. ERPs did not differ significantly between LTLE and RTLE patients, with respect to OLD/NEW distinction or the type of presented material (verbal vs. non-verbal). However, ERP topography showed significant differences between LTLE and RTLE patients: in lateral fronto-temporal recordings, patients showed larger negativities contralateral to the seizure focus, whereas we found larger negativities ipsilateral to the seizure focus in parietal recordings. Differences between the groups were significant from 300 to 600 ms post-stimulus. As a consequence, the amplitude gradient from fronto-temporal to parietal recordings was higher on the right side in LTLE patients and on the left side in RTLE patients. Again, differences between LTLE and RTLE patients were highly significant. We assume that ERPs reflect disturbances of a cortico-cortical network dependent on the side of the seizure focus in temporal lobe epilepsy. Furthermore, scalp-recorded ERPs might be a useful tool in the prediction of the side of the seizure focus in patients with temporal lobe epilepsy.


Visualization and genetic modification of resident brain microglia using lentiviral vectors regulated by microRNA-9.
Functional studies of resident microglia require molecular tools for their genetic manipulation. Here we show that microRNA-9-regulated lentiviral vectors can be used for the targeted genetic modification of resident microglia in the rodent brain. Using transgenic reporter mice, we demonstrate that murine microglia lack microRNA-9 activity, whereas most other cells in the brain express microRNA-9. Injection of microRNA-9-regulated vectors into the adult rat brain induces transgene expression specifically in cells with morphological features typical of ramified microglia. The majority of transgene-expressing cells colabels with the microglia marker Iba1. We use this approach to visualize and isolate activated resident microglia without affecting circulating and infiltrating monocytes or macrophages in an excitotoxic lesion model in rat striatum. The microRNA-9-regulated vectors described here are a straightforward and powerful tool that facilitates functional studies of resident microglia.


Influence of cardioplegic solution on incidence of delirium after CABG surgery: Use of Calafiore blood cardioplegia versus HTK - Bretschneider - solution in a single-center retrospective analysis from 2017 to 2021.
Purpose of the present study is an evaluation of postoperative incidence for delirium after coronary artery bypass surgery (CABG). Study addressed whether application of Histidine-Tryptophan-Ketoglutarate (HTK) solution (Bretschneider) or blood cardioplegia (Calafiore) is associated with increased of postoperative delirium cases. In a retrospective, single center evaluation a total number of 273 patients were enrolled in the study from January 2017 to October 2021. There were 124 patients assigned to the Calafiore group blood cardioplegic solution (BCC) and 149 patients were included in the Bretschneider group (HTK). The primary endpoint was the postoperative delirium rate in its frequency of occurrence. Definition of the dilirium status was performed using the Confusion Assessment Method in the Intensive Care Unit (CAM-ICU) score during the first three postoperative days. Secondary endpoints were the time intervals of intensive care duration of stay, mechanical ventilation, total extracorporeal circulation, ischemia and reperfusion. Serum levels of the electrolytes Sodium, Potassium, ionized Calcium, and Chloride were monitored. Although no significant difference in delirium status between the groups were noticed, on third postoperative day, delirium rate dependent on cardioplegia solution used (HTK 12.0%; BCC 3.0%; p = .024) and duration of intensive care stay differed (HTK 4.5 vs. BCC 3.0 days; p = .001). Although Ischemic time (HTK 73.0 vs. BCC 83.0 min; p < .001) and reperfusion time (HTK 35.0 vs. Calafiore 24.0 min; p < .001) were extended in the BCC group less cases of delirium were diagnosed. Serum sodium levels after HTK cardioplegic infusion were decreased (HTK 129.68 vs. BCC 138.96 mmol/l; p < .001). The significant difference persists up to the hundredth extracorporeal circulation circuit min (p = .005). The present data suggest an impact of the cardioplegic solution used upon postoperative delirium rates. Optimization of cardiac arrest protocols is needed. Present data encourage further prospective studies regarding the impact of cardioplegic solutions on electrolyte imbalance for postoperative delirium rates in CABG surgery.


Genetic variance and phenotypic plasticity in a component of female mate choice in an ultrasonic moth.
Female response to male advertisement signals in lesser waxmoths showed substantial genetic variation, phenotypic plasticity across rearing environments, and genotype-by-environment interactions resulting in crossing reaction norms. These results represent two previously underemphasized means by which genetic variation may be maintained in sexually selected traits: genetic variation in female response to male traits, and variation in the selection acting on both males and females. Genotype-by-environment interactions and reaction norms that cross indicate that divergent selection may act on male and female sexual traits if the level of environmental change is high. The processes that contribute to the maintenance of genetic variation may thus also contribute to population differentiation.


Efficacy of shared decision making on treatment satisfaction for patients with first-admission schizophrenia: study protocol for a randomised controlled trial.
Shared decision making is a promising model for patient-centred medicine, resulting in better clinical outcomes overall. In the mental health field, interventions that consider the patient-centred perspective--such as patient quality of life, involvement in the treatment, treatment satisfaction, and working alliance--have increased and better clinical outcomes discovered for patients with schizophrenia. However, few studies have examined the efficacy of shared decision making for schizophrenia treatment. The objective of this study is to evaluate the effect of a shared decision making intervention compared to treatment as usual on patient satisfaction at discharge for first-admission patients with schizophrenia. This is a randomised, parallel-group, two-arm, open-label, single-centre study currently being conducted in an acute psychiatric ward of Numazu Chuo Hospital, Japan. We are recruiting patients between 16 and 65 years old who are admitted to the ward with a diagnosis of schizophrenia without prior experience of psychiatric admission. Fifty-eight participants are being randomised into a shared decision making intervention group or a treatment as usual control group in a 1:1 ratio. The intervention program was developed based on a shared decision making model and is presented as a weekly course lasting the duration of the patients' acute psychiatric ward stay. The primary outcome measure is patient satisfaction at discharge as assessed by the Client Satisfaction Questionnaire. Due to the study's nature, neither the patient nor staff can be blinded. This is the first randomised controlled trial to evaluate the efficacy of shared decision making for patients with early-treatment-stage schizophrenia. The intervention program in this study is innovative in that it includes both of the patient and staff who are involved in the treatment. The study has been registered with ClinicalTrials.gov as NCT01869660.


Three-dimensional observations on the alterations of lobular architecture in chronic hepatitis with special reference to its angioarchitecture for a better understanding of the formal pathogenesis of liver cirrhosis.
For a better understanding of the formal pathogenesis of liver cirrhosis, the angioarchitecture of the liver lobule in chronic viral hepatitis was investigated three dimensionally. The histological reconstruction method, using serial histological sections, was adopted for the three-dimensional observation. Histology of the case showed chronic active hepatitis with occasional fibrous bridging of the portal to portal tract or hepatic vein. Graphic reconstructions revealed various degrees of altered angioarchitecture from place to place. While the conducting portion of the portal vein was almost preserved, the pathological changes mostly began at the parenchymal portion, especially second step or subsequent branches of the portal vein. In general, portal vein branches showed damage such as stenoses, disappearance, an increase and decrease in number and distorted spatial arrangements. Even in less damaged portal tracts, portal veins showed such changes to some extent. In severely damaged places with bridging fibrosis, a normal lobular angioarchitecture was completely lost; instead, portal veins, arteries and hepatic veins were tangled with each other. Parenchymal nutrition was suggested to be dependent on the remaining third-step portal branches or newly formed ones. However, the hepatic vein system had a tendency to be preserved and distributed fluently in the parenchyma. The distortion of these portal vessels indicated various degrees of loss of the lobular architecture. In conclusion, it is suggested that an early histological sign of cirrhosis develops in the course of chronic hepatitis.


Identification of prostaglandin D2 as a major prostaglandin in homogenates of rat brain.
Prostaglandin (PG) E2, D2, F2alpha and thromboxane B2 (TxB2) were determined in homogenates of rat brain by gas-chromatography--mass spectrometry. The level of PGD2 was 735 +/- 19 ng/g, of PGF2alpha 150 +/- 13 ng/g, of TxB2 112 ng/g and of PGE2 86 +/- 8 ng/g. The same relative proportions of cyclooxygenase products were found in incubates of unstimulated sliced rat brain. 14C-PGH2 was converted in high yield into PGD2 by enzyme(s) present in the soluble fraction of the homogenate. These results indicate that PGD2 is the major cyclooxygenase product in the central nervous system of the rat.


The nutritional status and dietary pattern of Chinese adolescents, 1991 and 1993.
To increase understanding about current dietary patterns and short-term relationships between economic change and adolescent nutrition in a lower-income country, using the 1991 and 1993 China Health and Nutrition Survey data. Cross-sectional study. Eight provinces in China that vary substantially in geography, economic development, public resources, and health indicators. 2236 and 2018 adolescents aged 10-18 years who completed three 24-hour recalls in the 1991 and 1993 survey, respectively. Chinese adolescents experienced an improvement of diet and nutritional status. The prevalence of stunting declined from 23% in 1991 to 19% in 1993. Under-nutrition was a problem of concern although the prevalence (12-13%) was relatively low. Overweight was emerging as a problem associated with young, high-income and urban adolescents, but the prevalence (4%) was quite low compared with developed countries. Chinese adolescents' energy and protein intakes were adequate compared with the American RDA. About 27% of the participants derived more than 30% of their dietary energy from fat and 16% of them derived over 10% of energy from saturated fat by 1993. Chinese adolescents have experienced an improvement in diet and nutritional status, but undernutrition is still an important nutrition problem, especially among young and poor groups. More attention should focus on the increase of dietary fat intake and obesity.


Effect of Acute High-Intensity Interval Training on Immune Function and Oxidative Stress in Canoe/Kayak Athletes.
The aim of this study was to investigate the effects of acute high-intensity interval training (HIIT) on immune function and oxidative stress in male canoe/kayak athletes who were well trained. A total of 22 participants were voluntarily recruited with an age range of 15.9 ± 2.3 years, height of 172.2 ± 5.5 cm, body mass of 63.30 ± 6.95 kg, and body fat of 13.77 ± 3.76%. The modified Wingate kayaking test on a kayak ergometer was performed by all participants. Blood samples were collected at three different time points: before the test (Pre-T), immediately after (Post-T), and 3 h post-test (Post-3 h). Saliva samples were collected at two different time points: before the test (Pre-T) and 3 h after the test (Post-3 h). Results indicated that acute canoe/kayak ergometry HIIT had significant effects on the percentages and counts of leukocytes, neutrophils, lymphocytes, and lymphocyte subsets. Additionally, it resulted in increased total LPS-stimulated neutrophil elastase release and alterations in plasma concentrations of superoxide dismutase, catalase, and TBARS. These findings suggest that conventional kayak HIIT regimens can have short-term effects on immune function and induce oxidative stress in athletes.


Comparison between 3-point Dixon- and CHESS-based OMERACT-recommended MRI protocols in hands of patients with suspicion of early rheumatoid arthritis.
To compare fat suppression effectiveness, image quality and disease activity scores between MRI protocols based on the Dixon method and the Chemical Shift Selective (CHESS) technique in hands of patients with suspicion of early rheumatoid arthritis (RA). Both hands of 28 patients (19 women; mean age 45.2 years old) with suspicion of early RA were prospectively imaged with Dixon- and CHESS-based OMERACT recommended protocols at 1.5 T including fat-suppressed T2-weighted and contrast-enhanced T1-weighted imaging. Two radiologists (R1/R2) separately assessed effectiveness of fat suppression and determined RAMRIS scores woth the Dixon- and CHESS-based protocols. R1 repeated the RAMRIS scoring and measured contrast-to-noise ratios (CNRs) on Dixon and CHESS images. Statistics included 2-way ANOVA test for the comparison of CNRs and Bland-Altman methodology for inter-technique and intra-observer agreement (p < 0.05). Fat suppression failure occurred in up to 1 patient with the Dixon- and 25 patients with the CHESS-based protocols. CNRs were significantly higher on T1-weighted and lower on T2-weighted Dixon images than on the corresponding CHESS images (p ≤ 0.042). Median bias of the difference between Dixon- and CHESS-based RAMRIS scores was not significantly different from 0 (-0.8 to +1.0 and -1.1 to +1.4 for R1/R2). Median bias of the difference between RAMRIS scores at first and second readings was significantly different from 0 with the CHESS-based protocols (-0.8 to +1.7) but not with the Dixon-based protocols (+0.0 to +1.0). Dixon sequences yield more effective fat suppression and more reproducible RAMRIS scoring than CHESS sequences in hands with suspicion of early RA.


Quantification of Conflicts of Interest in an Online Point-of-Care Clinical Support Website.
Online medical reference websites are utilized by health care providers to enhance their education and decision making. However, these resources may not adequately reveal pharmaceutical-author interactions and their potential conflicts of interest (CoIs). This investigation: (1) evaluates the correspondence of two well-utilized CoI databases: the Centers for Medicare and Medicaid Services Open Payments (CMSOP) and ProPublica's Dollars for Docs (PDD) and (2) quantifies CoIs among authors of a publicly available point of care clinical support website which is used to inform evidence-based medicine decisions. Two data sources were used: the hundred most common drugs and the top fifty causes of death. These topics were entered into a freely available database. The authors (N = 139) were then input into CMSOP and PDD and compensation and number of payments were determined for 2013-2015. The subset of highly compensated authors that also reported "Nothing to disclose" were further examined. There was a high degree of similarity between CMSOP and PDD for compensation (R2 ≥ 0.998) and payment number (R2 ≥ 0.992). The amount received was 1.4% higher in CMSOP ($4,059,194) than in PDD ($4,002,891). The articles where the authors had received the greatest compensation were in neurology (Parkinson's Disease = $1,810,032), oncology (Acute Lymphoblastic Leukemia = $616,727), and endocrinology (Type I Diabetes = $377,388). Two authors reporting "Nothing to disclose" received appreciable and potentially relevant compensation. CMSOP and PDD produced almost identical results. CoIs were common among authors but self-reporting may be an inadequate reporting mechanism. Recommendations are offered for improving the CoI transparency of pharmaceutical-author interactions in point-of-care electronic resources.


Convective heat transfer characteristics of toothed leaves.
Model leaves were used to test the hypothesis that serrate leaves have more convective heat loss than entire leaves of the same average size. Convection coefficients were positively correlated with size of teeth, supporting the hypothesis. Experimental results were in close agreement with theoretical predictions, which assumed an inverse correlation between depth of serration and effective leaf dimension.


Peptide-Targeted Polyplexes for Aerosol-Mediated Gene Delivery to CD49f-Overexpressing Tumor Lesions in Lung.
Peptide ligands can enhance delivery of nucleic acid-loaded nanoparticles to tumors by promoting their cell binding and internalization. Lung tumor lesions accessible from the alveolar side can be transfected, in principle, using gene vectors delivered as an aerosol. The cell surface marker CD49f (Integrin α6) is frequently upregulated in metastasizing, highly aggressive tumors. In this study, we utilize a CD49f binding peptide coupled to linear polyethylenimine (LPEI) promoting gene delivery into CD49f-overexpressing tumor cells in vitro and into lung lesions in vivo. We have synthesized a molecular conjugate based on LPEI covalently attached to the CD49f binding peptide CYESIKVAVS via a polyethylene glycol (PEG) spacer. Particles formed with plasmid DNA were small (<200 nm) and could be aerosolized without causing major aggregation or particle loss. In vitro, CD49f targeting significantly improved plasmid uptake and reporter gene expression on both human and murine tumor cell lines. For evaluation in vivo, localization and morphology of 4T1 murine triple-negative breast cancer tumor lesions in the lung of syngeneic BALB/c mice were identified by MRI. Polyplexes applied via intratracheal aerosolization were well tolerated and resulted in measurable transgene activity of the reporter gene firefly luciferase in tumor areas by bioluminescence imaging (BLI). Transfectability of tumors correlated with their accessibility for the aerosol. With CD49f-targeted polyplexes, luciferase activity was considerably increased and was restricted to the tumor area.


Twenty years' experience in allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in the Nagoya Blood and Marrow Transplantation Group.
Between October 1981 and December 2000, 46 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) underwent allogeneic hematopoietic stem cell transplantation (HSCT) in the Nagoya Blood and Marrow Transplantation Group. The median age was 28.5 years (range, 4-51 years). All but one patient achieved engraftment. Grade II-to-IV acute graft-versus-host disease (GVHD) developed in 32.5% of patients, and chronic GVHD developed in 40.5%. The incidences of relapse and treatment-related mortality (TRM) at 5 years were 65% and 26%, respectively. The estimated overall survival rate at 5 years was 23%. Univariate analysis showed that improved disease-free survival (DFS) was independently associated with complete remission (CR) at transplantation (39%), compared with non-CR (8%) (P = .023). Non-CR at transplantation was associated with a higher risk of relapse. Donor type, acute GVHD, and time from diagnosis to HSCT all had a significant effect on TRM. In a multivariate analysis, 9 months or more from diagnosis to HSCT was the only variable statistically significant for DFS (relative risk, 3.22; P = .01). This study demonstrates that allogeneic HSCT cures a significant population of patients with Ph+ ALL. Relapse is the major obstacle limiting the success of HSCT. Early transplantation during CR from donors, including unrelated persons or mismatched relatives, may offer improved long-term DFS.


Presence of human papillomavirus infection of the uterine cervix as determined by different detection methods in a low-risk community-based population.
To evaluate the effectiveness of various screening tests for detecting genital human papillomavirus (HPV) in a community-based population and to determine the prevalence of cervical lesions on colposcopically directed biopsies in patients found to have HPV by any screening test. Cross-sectional analysis of 208 female patients screened for HPV by clinical examination, Papanicolaou test, dot blot hybridization test (ViraPap, Digene Inc, Silver Spring, Md), and polymerase chain reaction (PCR) analysis. All persons with abnormal or positive results by any method were offered colposcopic evaluation. Two community-based family practice offices in southeastern Michigan. The presence of HPV as determined by each test and results of colposcopic biopsies (gold standard) in patients who had HPV identified by any test. The prevalence of HPV infection was 20.3% by PCR analysis, 3.1% by ViraPap, 3.0% by the Papanicolaou test, and 0% by clinical examination. Symptomatic patients (those with complaints of vaginal odor, swelling, or itching) were more likely to harbor HPV as determined by PCR analysis than were asymptomatic women (P = .03, odds ratio = 2.65). Human papillomavirus type 16 or 18 was found in 41% of patients with positive PCR analyses and in all patients with positive ViraPap tests that were typed. Colposcopy with biopsy (gold standard for the presence of HPV disease) was performed on 34 of the 41 patients who tested positive for HPV by PCR analysis. Histologic results revealed that 79.4% of these patients had cervical disease: 14.6% had cervical intraepithelial neoplasia, 38.3% had condyloma, and 26.5% had cervicitis. Human papillomavirus as detected by PCR analysis was present in 20.3% of women in our population and was often one of the higher-risk types (16 or 18). A positive PCR analysis was predictive of cervical disease on colposcopic biopsy. The ViraPap test, Papanicolaou test, and clinical examination were insensitive measures for detecting HPV-related lesions in this population.


Reconstitution of oxygen evolution in high salt washed photosystem II particles.
Photosystem II thylakoid particles possessing high rates of oxygen evolution, were shown to have a very simple polypeptide composition. Upon washing of these particles with 250 mM NaCl the oxygen evolution was inhibited up to 80% concomitant with a release of two polypeptides of 23 and 16 kDa. Readdition of the pure 23 kDa protein to the depleted thylakoids under low ionic strength reconstituted more than half of the lost activity. No stimulation was obtained with the 16 kDa protein alone or in combination with glycerol. The results give further strong evidence that the 23 kDa protein is an essential component in the oxygen evolving complex. The possible involvement of other proteins in this complex is discussed in light of the demonstrated simple polypeptide pattern of the photosystem II particles.


Achieving efficacy in subjects with sustained pegvaliase-neutralizing antibody responses.
Pegvaliase (Palynziq®) is an enzyme substitution therapy using PEGylated recombinant Anabaena variabilis phenylalanine ammonia lyase (PAL) to reduce blood phenylalanine (Phe) levels in adults with phenylketonuria (PKU). In Phase 3 clinical studies, all subjects treated with pegvaliase developed anti-drug antibodies. To specifically evaluate pegvaliase-neutralizing antibodies (NAbs) and assess impact on pegvaliase efficacy, a novel hybrid ligand-binding/tandem mass spectrometry NAb assay was developed. Analysis of Phase 3 study samples revealed that pegvaliase NAb titers developed during early treatment (≤6 months after treatment initiation), and then plateaued and persisted in the majority of subjects during late treatment (>6 months). Subjects with the lowest/undetectable NAb titers had relatively high plasma pegvaliase concentrations and experienced the most rapid decline in blood Phe concentrations at relatively low pegvaliase dose concentrations. In contrast, subjects with higher NAb titers generally had lower plasma pegvaliase concentrations on similar low doses, with little change in blood Phe concentrations. However, with additional time on treatment and individualized dose titration, the majority of subjects achieved substantial and sustained blood Phe reduction, including those with higher NAb titers. Moreover, after maturation of the anti-pegvaliase immune response, NAb titers were stable over time and did not rise in response to dose increases; thus, subjects did not require additional dose increases to maintain reduction in blood Phe.


Opiate and Cerebral Atrophy.
How to cite this article: Zirpe K, Bamne SN. Opiate and Cerebral Atrophy. Indian J Crit Care Med 2020;24(4):218-219.


Effect of cholecystectomy on mouth-to-cecum transit of a liquid meal.
Mouth-to-cecum transit and serum bile acid profile after ingestion of a lactulose-labeled liquid meal (440 kcal) were measured in eight patients with gallstones and a radiologically functioning gallbladder before and three to five months after cholecystectomy and in 15 controls. In the patients mouth-to-cecum transit was longer after the operation, 87.5 +/- 18.5 (mean +/- SEM) min vs 57.5 +/- 9.7 min (P less than 0.05). Mouth-to-cecum transit times before and after the operation were not different from controls (58.0 +/- 6.7 min). Serum bile acid AUCs were similar (P = NS) in patients and controls, while total bile acid and cholylglycine fasting concentrations were higher after cholecystectomy (P less than 0.05 and P less than 0.01 respectively). Cholecystectomy prolongs mouth-to-cecum transit of a liquid meal.


Epidemiological analysis of Salmonella enterica from beef sampled in the slaughterhouse and retailers in Dakar (Senegal) using pulsed-field gel electrophoresis and antibiotic susceptibility testing.
Seventy-eight isolates of Salmonella spp. isolated from beef sampled from the official city slaughterhouse and from retailers in Dakar, Senegal were analyzed using serotyping, antimicrobial testing and macrorestriction profiling by Pulsed-Field Gel Electrophoresis (PFGE). These analyses were done to identify clonal relationships and potential transmission routes in beef channel. XbaI macrorestriction allowed defining 17 genotypes among the six main analyzed serotypes: Salmonella bredeney (3 genotypes), S. muenster (6), S. waycross (1), S. corvallis (3), S. kentucky (1) and S. brandenburg (3). The cross analysis of PFGE profiles and origin of the beef samples reveals a wide range of contamination sources in the beef channel in Dakar. Comparison of PFGE and antimicrobial resistance types shows that the Salmonella contamination sources are equally shared by the slaughterhouse (56% of the isolates) and by the distribution channel (44% of the isolates) by handlings and houseflies.


Emotional modulation of pain and spinal nociception in persons with major depressive disorder (MDD).
Major depressive disorder (MDD) is associated with risk for chronic pain, but the mechanisms contributing to the MDD and pain relationship are unclear. To examine whether disrupted emotional modulation of pain might contribute, this study assessed emotional processing and emotional modulation of pain in healthy controls and unmedicated persons with MDD (14 MDD, 14 controls). Emotionally charged pictures (erotica, neutral, mutilation) were presented in 4 blocks. Two blocks assessed physiological-emotional reactions (pleasure/arousal ratings, corrugator electromyography (EMG), startle modulation, skin conductance) in the absence of pain and 2 blocks assessed emotional modulation of pain and the nociceptive flexion reflex (NFR, a physiological measure of spinal nociception) evoked by suprathreshold electric stimulations. Results indicated pictures generally evoked the intended emotional responses; erotic pictures elicited pleasure, subjective arousal, and smaller startle magnitudes, whereas mutilation pictures elicited displeasure, corrugator EMG activation, and subjective/physiological arousal. However, emotional processing was partially disrupted in MDD, as evidenced by a blunted pleasure response to erotica and a failure to modulate startle according to a valence linear trend. Furthermore, emotional modulation of pain was observed in controls but not MDD, even though there were no group differences in NFR threshold or emotional modulation of NFR. Together, these results suggest supraspinal processes associated with emotion processing and emotional modulation of pain may be disrupted in MDD, but brain to spinal cord processes that modulate spinal nociception are intact. Thus, emotional modulation of pain deficits may be a phenotypic marker for future pain risk in MDD.


Perfluorooctane sulfonic acid modulates expression of placental steroidogenesis-associated genes and hormone levels in pregnant rats.
Perfluorooctane sulfonate (PFOS) is a widespread and persistent chemical in the environment. Reports show that PFOS is a potential endocrine disruptor; however, the possible effects of PFOS on placental endocrine function are unclear. This study aimed to investigate the endocrine-disrupting effects of PFOS on the placenta in pregnant rats and its potential mechanism. Pregnant rats from gestational days 4-20 were exposed to 0, 10, and 50 μg/mL PFOS through drinking water followed by analysis of various biochemical parameters. PFOS dose-dependently decreased fetal and placental weight in both sexes, with a specific decrease in weight of labyrinth but not junctional layer. Plasma progesterone (↑166%), aldosterone (↑201%), corticosterone (↑205%), testosterone (↑45%), luteinizing hormone (↑49%) levels were significantly increased, while estradiol (↓27%), prolactin (↓28%) and hCG (↓62%) levels were reduced in groups exposed to higher doses of PFOS. Real-time quantitative reverse transcriptase-polymerase chain reaction analysis revealed a significant increase in mRNA levels of placental steroid biosynthesis enzymes, including Cyp11A1 and 3β-HSD1 in male placenta and StAR, Cyp11A1, 17β-HSD1 and 17β-HSD3 in female placenta of PFOS dams. Cyp19A1 expression in ovaries was significantly decreased in PFOS dams. mRNA levels for placental steroid metabolism enzyme UGT1A1 increased in male but not in female placenta of PFOS dams. These results suggest that the placenta is a target tissue of PFOS and PFOS-induced dysregulation in steroid hormone production might be related to the altered expression of hormone biosynthesis and metabolism enzyme genes in the placenta. This hormone disruption might affect maternal health and fetal growth.


Loss of growth hormone-dependent characteristics of rat hepatocytes in culture.
The liver of rodents is sexually differentiated, i.e. the female liver differs from the male liver. This differentiation is largely controlled by the pattern of growth hormone (GH) secretion. We have attempted to maintain GH-dependent differentiation of cultured rat hepatocytes. We examined the level of alcohol dehydrogenase (ADH) activity, which responds to GH and is higher in female than in male liver, and the estrogen receptor, which is dependent on GH but is present is equal amounts in males and females. ADH activity was maintained in cells from male rats, but fell by 40% in cells from females in medium supplemented with insulin and dexamethasone. The estrogen receptor content of female cells fell dramatically to undetectable levels within 2 d of culture. Extensive supplementation of the medium failed to prevent the decrease in ADH activity in female cells; similarly, the addition of female sex steroids; rat serum; pituitary extracts; rat, human, or bovine GH; or ovine prolactin failed to maintain the enzyme activity. Insulin, dexamethasone, thyroid hormone plus GH or prolactin, or the combination of all five hormones also failed to prevent the loss of estrogen receptors. Short-term cultures of rat hepatocytes, although retaining the liver-specific expression of ADH at the male level, lose GH-dependent expression of the estrogen receptor and stimulation of ADH activity.


Inflammatory Myofibroblastic Tumor After Treatment of Wilms Tumor in a 6-Year-Old Boy: A Case Report and Literature Review.
Inflammatory myofibroblastic tumor (IMT) is a rare tumor with an indolent course. It is less often reported as a second tumor that occurs after treatment of malignant tumors in pediatric patients. Here, we report a case of IMT following Wilms tumor (WT), and conduct a literature review concerning IMTs and WT to evaluate the diagnostic possibility of IMT as a second tumor. The coexistence of the 2 tumors may cause confusion as to whether they share genetic links or that IMTs may appear as late effects of the treatment of WT.


Metagenomic Studies in Inflammatory Skin Diseases.
Next-generation sequencing (NGS) technologies together with an improved access to compute performance led to a cost-effective genome sequencing over the past several years. This allowed researchers to fully unleash the potential of genomic and metagenomic analyses to better elucidate two-way interactions between host cells and microbiome, both in steady-state and in pathological conditions. Experimental research involving metagenomics shows that skin resident microbes can influence the cutaneous pathophysiology. Here, we review metagenome approaches to study microbiota at this barrier site. We also describe the consequences of changes in the skin microbiota burden and composition, mostly revealed by these technologies, in the development of common inflammatory skin diseases.


Understanding Breast-Cancer-Associated Fibroblasts and Their Epigenetic Activation to Unveil Novel Targets for Breast Cancer Therapy.
The review article 'Cancer-Associated Fibroblasts: Epigenetic Regulation and Therapeutic Intervention in Breast Cancer' by Lee et al [...].


LYVE1+ macrophages of murine peritoneal mesothelium promote omentum-independent ovarian tumor growth.
Two resident macrophage subsets reside in peritoneal fluid. Macrophages also reside within mesothelial membranes lining the peritoneal cavity, but they remain poorly characterized. Here, we identified two macrophage populations (LYVE1hi MHC IIlo-hi CX3CR1gfplo/- and LYVE1lo/- MHC IIhi CX3CR1gfphi subsets) in the mesenteric and parietal mesothelial linings of the peritoneum. These macrophages resembled LYVE1+ macrophages within surface membranes of numerous organs. Fate-mapping approaches and analysis of newborn mice showed that LYVE1hi macrophages predominantly originated from embryonic-derived progenitors and were controlled by CSF1 made by Wt1+ stromal cells. Their gene expression profile closely overlapped with ovarian tumor-associated macrophages previously described in the omentum. Indeed, syngeneic epithelial ovarian tumor growth was strongly reduced following in vivo ablation of LYVE1hi macrophages, including in mice that received omentectomy to dissociate the role from omental macrophages. These data reveal that the peritoneal compartment contains at least four resident macrophage populations and that LYVE1hi mesothelial macrophages drive tumor growth independently of the omentum.


Immune responses in the lung: basic principles.
The basic elements which regulate immunomodulation at the lung level and the constituents of in situ pulmonary host defense mechanisms that recognize, destroy, and remove potentially harmful inhaled antigenic materials are discussed. The relevance of these processes in term of pathogenesis of some lung disorders is briefly exemplified.


Activation of the essential kinase PDK1 by phosphoinositide-driven trans-autophosphorylation.
3-phosphoinositide-dependent kinase 1 (PDK1) is an essential serine/threonine protein kinase, which plays a crucial role in cell growth and proliferation. It is often referred to as a 'master' kinase due to its ability to activate at least 23 downstream protein kinases implicated in various signaling pathways. In this study, we have elucidated the mechanism of phosphoinositide-driven PDK1 auto-activation. We show that PDK1 trans-autophosphorylation is mediated by a PIP3-mediated face-to-face dimer. We report regulatory motifs in the kinase-PH interdomain linker that allosterically activate PDK1 autophosphorylation via a linker-swapped dimer mechanism. Finally, we show that PDK1 is autoinhibited by its PH domain and that positive cooperativity of PIP3 binding drives switch-like activation of PDK1. These results imply that the PDK1-mediated activation of effector kinases, including Akt, PKC, Sgk, S6K and RSK, many of whom are not directly regulated by phosphoinositides, is also likely to be dependent on PIP3 or PI(3,4)P2.


Kloeckera apis st. nov.; the imperfect state of Hanseniaspora guilliermondii Pijper.
K. apiculata var. apis (nom. nud.) was found to be the imperfect state of H. guilliermondii Pijper by a high degree of DNA reassociation. The name is validated and raised to species rank, K. apis Lavie ex Smith, Simione and Meyer. K. apis and H. guilliermondii could be distinguished from H. uvarum and H. valbyensis by a low DNA reassociation and by growth at 37 C.