Function and Regulation of the Calcium-Activated Chloride Channel Anoctamin 1 (TMEM16A).
Various human tissues express the calcium-activated chloride channel Anoctamin 1 (ANO1), also known as TMEM16A. ANO1 allows the passive chloride flux that controls different physiological functions ranging from muscle contraction, fluid and hormone secretion, gastrointestinal motility, and electrical excitability. Overexpression of ANO1 is associated with pathological conditions such as hypertension and cancer. The molecular cloning of ANO1 has led to a surge in structural, functional, and physiological studies of the channel in several tissues. ANO1 is a homodimer channel harboring two pores - one in each monomer - that work independently. Each pore is activated by voltage-dependent binding of two intracellular calcium ions to a high-affinity-binding site. In addition, the binding of phosphatidylinositol 4,5-bisphosphate to sites scattered throughout the cytosolic side of the protein aids the calcium activation process. Furthermore, many pharmacological studies have established ANO1 as a target of promising compounds that could treat several illnesses. This chapter describes our current understanding of the physiological roles of ANO1 and its regulation under physiological conditions as well as new pharmacological compounds with potential therapeutic applications.


Ameloblastic carcinoma: a multicenter Nigerian study.
To obtain a national profile on the prevalence and management of ameloblastic carcinoma in Nigerians. Data were collected from the case files of patients with a histologic diagnosis of ameloblastic carcinoma from 4 tertiary referral centers in Nigeria from January 1980 to December 2008. Twenty patients were seen within the study period. There were 11 male and 9 female patients, with a male-to-female ratio of 1.2:1. Their ages ranged from 16 to 85 years (mean +/- SD, 41.63 +/- 19.8 years). The duration of the lesion before presentation was 6 months to 4 years. Twelve cases occurred in the posterior mandible alone, 1 case occurred in the anterior mandible alone, and 4 cases involved the anterior and posterior mandible. The posterior part of the maxilla was involved in 3 cases. A majority of the cases (17) occurred de novo, and 3 patients presented with carcinoma ex-ameloblastoma. Treatment included surgical resection with or without neck dissection. Eight patients declined treatment after diagnosis. Surgery was planned for 12 patients, but 2 patients died of intractable bleeding episodes before surgery. Mandibulectomies and maxillectomies were performed for 10 patients. Follow-up was carried out for 5 patients. Recurrence ranged from 6 to 96 months after the first surgery. Overall deaths recorded involved 6 patients. Three patients died within 3 years after the initial surgery and 1 patient died about 8 years after the initial surgery. One patient is still alive and well 1 year after surgery. Ameloblastic carcinoma is an uncommon malignancy. Most cases occur in the mandible and arise de novo. Early diagnosis and radical local excision remain the mainstay of treatment.


Possible multiple binding sites for o-aminophenol on uridine diphosphate glucuronyltransferase.
1. Hepatic microsomal UDP-glucuronyltransferase (EC 184.108.40.206) derived from either weanling or adult rats exhibits three pH optima, at pH 5.4, 7.2 and 9.2, when o-aminophenol is the acceptor substrate, whereas p-nitrophenol is the acceptor substrate only on pH optimum is observed, at pH 5.4.2. Prior treatment of rats of either age with 3-methylcholanthrene results in a 2-3-fold increase in o-aminophenol conjugation at pH 5.4 and a 6-9-fold increase at pH 9.2. At pH 7.2, the induced enzyme is 2 to 3 times more active towards o-aminophenol than the control enzyme, but no pH optimum is demonstrable. 3. o-Aminophenol conjugation at pH 5.4 and 9.2 is inhibited competitively by both p-nitrophenol and p-nitrophenyl glucuronide, suggesting that the two phenolic aglycones share the same binding site. At pH 7.2, however, p-nitrophenyl glucuronide does not inhibit o-aminophenol conjugation, suggesting that the binding site at this pH is not shared by the two phenols. These data are consistent with the existence of more than one binding site for o-aminophenol on UDP-glucuronyltransferase.


Peripheral and central effects of repeated social defeat stress: monocyte trafficking, microglial activation, and anxiety.
The development and exacerbation of depression and anxiety are associated with exposure to repeated psychosocial stress. Stress is known to affect the bidirectional communication between the nervous and immune systems leading to elevated levels of stress mediators including glucocorticoids (GCs) and catecholamines and increased trafficking of proinflammatory immune cells. Animal models, like the repeated social defeat (RSD) paradigm, were developed to explore this connection between stress and affective disorders. RSD induces activation of the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis activation, increases bone marrow production and egress of primed, GC-insensitive monocytes, and stimulates the trafficking of these cells to tissues including the spleen, lung, and brain. Recently, the observation that these monocytes have the ability to traffic to the brain perivascular spaces and parenchyma have provided mechanisms by which these peripheral cells may contribute to the prolonged anxiety-like behavior associated with RSD. The data that have been amassed from the RSD paradigm and others recapitulate many of the behavioral and immunological phenotypes associated with human anxiety disorders and may serve to elucidate potential avenues of treatment for these disorders. Here, we will discuss novel and key data that will present an overview of the neuroendocrine, immunological and behavioral responses to social stressors.


[Human T-lymphotrophic retroviruses].
Investigations of retroviruses, possible etiological agents of T-cell human leukemias and acquired immunodeficiency syndrome are reviewed. Main attention is paid to the genome structure and function.


Nrf2 induces cisplatin resistance via suppressing the iron export related gene SLC40A1 in ovarian cancer cells.
Induction of Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) has been demonstrated to be involved in cisplatin resistance in ovarian cancer. Solute carrier family 40 member 1 (SLC40A1) is an iron exporter, which possesses many putative Nrf2 binding sites. Here we hypothesize that it may be a possible downstream gene of Nrf2. Elevated level of Nrf2 and reduced level of SLC40A1 were found in cisplatin-resistant ovarian cancer cells as compared with cisplatin-sensitive ovarian cancer cells. Exogenous knockdown of Nrf2 leaded to increased expression of SLC40A1. While overexpression of Nrf2 resulted in decreased expression of SLC40A1. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assay revealed that Nrf2 inhibited the transcription of SLC40A1. Overexpression of SLC40A1 was able to reverse cisplatin resistance induced by Nrf2, while knockdown of SLC40A1 restored cisplatin resistance and increased iron concentration. Desferal, an iron chelator, was found to overcome cisplatin resistance through iron deprivation. Its function was boosted when combined with brusatol, an Nrf2 inhibitor. Taken together, this study first demonstrated that Nrf2 could transcriptionally suppress the expression of SLC40A1. Iron overload induced by SLC40A1 resulted in cisplatin resistance in ovarian cancer. Targeting iron metabolism may be a new therapeutic strategy to reverse drug resistance in ovarian cancer treatment.


[Effect of hardness and surface quality of metal cones on fracture load of ceramic ball heads of hip endoprostheses].
The safety of ceramic ball heads attached to hip endoprostheses by means of a conical fitting requires that the connection be designed with the ceramic material in mind. The ISO 7206-5 standard describes a static testing protocol to measure the maximal loading limit of the conical connection. In order to achieve high fracture loads in this test, it is necessary to optimize the load-bearing parts of the connection to prevent stress concentrations, to which the ceramic ball is sensitive. For this reason, manufacturers of ceramic balls give their customers specifications for the design of the metal taper, specifying tolerances for angle, roughness, roundness and straightness. In order to investigate which parameters of the metal taper have an influence on the fracture load achievable according to ISO 7206-5, fracture load tests were conducted with zircon oxide (ZIOLOX) heads in combination with test tapers from various manufacturers. The test tapers were made of Ti- or CoCr-based alloys. Before the tests the tapers were completely measured and characterized according to geometric parameters of roughness, roundness, straightness, profile and angle, and physical parameters such as hardness and elastic modulus. Subsequent measurements after the fracture tests characterized changes that occurred in the metal tapers. The fracture loads achieved depended on the potential for deformation of the taper surface. This potential can be described by a factor computed as hardness/roughness. A dependence of the fracture load on elastic modulus, form deviations or taper angle could not be established within the Cerasiv specifications.


Cancer morbidity in subjects occupationally exposed to high frequency (radiofrequency and microwave) electromagnetic radiation.
Cancer morbidity was registered in the whole population of military career personnel in Poland during a period of 15 years (1971-1985). Subjects exposed occupationally to radiofrequencies (RF) and microwaves (MW) were selected from the population on the basis of their service records and documented exposures at service posts. The population size varied slightly from year to year with a mean count of about 128,000 persons each year; each year about 3700 of them (2.98%) were considered as occupationally exposed to RF/MW. All subjects (exposed and non-exposed to RF/MW) were divided into age groups (20-29, 30-39, 40-49 and 50-59). All newly registered cases of cancer were divided into 12 types based on localisation of the malignancy; for neoplasms of the haemopoietic system and lymphatic organs an additional analysis based on diagnosis was performed. Morbidity rates (per 100,000 subjects annually) were calculated for all of the above localisations and types of malignancies both for the whole population and for the age groups. The mean value of 15 annual rates during 1971-1985 represented the respective morbidity rate for the whole period. Morbidity rates in the non-exposed groups of personnel were used as 'expected' (E) rates for the exposed subjects, while the real morbidity rates counted in the RF/MW-exposed personnel served as 'observed' (O) rates. This allowed the calculation of the observed/expected ratio (OER) representing the odds ratio for the exposed groups. The cancer morbidity rate for RF/MW-exposed personnel for all age groups (20-59 years) reached 119.1 per 100,000 annually (57.6 in non-exposed) with an OER of 2.07, significant at P < 0.05. The difference between observed and expected values results from higher morbidity rates due to neoplasms of the alimentary tract (OER = 3.19-3.24), brain tumours (OER = 1.91) and malignancies of the haemopoietic system and lymphatic organs (OER = 6.31). Among malignancies of the haemopoietic/lymphatic systems, the largest differences in morbidity rates between exposed and non-exposed personnel were found for chronic myelocytic leukaemia (OER = 13.9), acute myeloblastic leukaemia (OER = 8.62) and non-Hodgkin lymphomas (OER = 5.82).


Characterization of Five Novel Anti-MRSA Compounds Identified Using a Whole-Animal Caenorhabditis elegans/Galleria mellonella Sequential-Screening Approach.
There is a significant need to combat the growing challenge of antibacterial drug resistance. We have previously developed a whole-animal dual-screening platform that first used the nematode Caenorhabditis elegans, to identify low-toxicity antibacterial hits in a high-throughput format. The hits were then evaluated in the wax moth caterpillar Galleria mellonella infection model to confirm efficacy and low toxicity at a whole animal level. This multi-host approach is a powerful tool for revealing compounds that show antibacterial effects and relatively low toxicity at the whole organism level. This paper reports the use of the multi-host approach to identify and validate five new anti-staphylococcal compounds: (1) 4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol(PPT), (2) (1S,2S)-2-[2-[[3-(1H-benzimidazol-2-yl)propyl]methylamino]ethyl]-6-fluoro-1,2,3,4-tetrahydro-1-(1-methylethyl)-2-naphthalenyl cyclopropanecarboxylate dihydrochloride(NNC), (3) 4,5,6,7-tetrabromobenzotriazole (TBB), (4) 3-[2-[2-chloro-4-[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methoxy]phenyl]ethenyl] benzoic acid(GW4064), and (5) N-(cyclopropylmethoxy)-3,4,5-trifluoro-2-[(4-iodo-2-methylphenyl)amino] benzamide(PD198306). The compounds reduced the severity of methicillin-resistant Staphylococcus aureus (MRSA, strain MW2) infections in both C. elegans and G. mellonella and showed minimal inhibitory concentrations (MICs) in the range of 2-8 µg/mL. Compounds NNC, PPT, and TBB permeabilized MRSA-MW2 cells to SYTOX green, suggesting that they target bacterial membranes. Compound TBB showed synergistic activity with doxycycline and oxacillin against MRSA-MW2, and compounds PPT, NNC, GW4064, and PD198306 synergized with doxycycline, polymyxin-B, gentamicin, and erythromycin, respectively. The study demonstrates the utility of the multi-host approach with follow-up hit characterization for prioritizing anti-MRSA compounds for further evaluation.


[Arterial hypertension and ischemic heart disease: clinico-echocardiographic aspects].
Doppler M-mode echocardiography was made in 156 males with ischemic heart disease (IHD) verified coronarographically. The patients were normotensive or had mild, moderate and severe arterial hypertension (AH) (groups 1, 2, 3 and 4, respectively). The groups were similar by functional anginal class. Echocardiographic findings were in many cases similar. This supports the hypothesis that IHD and AH are closely related. However, the addition of AH to atherosclerotic affection of the coronary artery or atherosclerosis rise in the presence of AH is associated with development of myocardial hypertrophy which is registered at echocardiography and correlates in severity with severity of AH. Myocardial hypertrophy is, on the one side, compensatory as it prevents dilation of the left ventricle and impairment of its contractility rising at later stage of the disease with depletion of the myocardial and coronary reserves, but, on the other side, it promotes diastolic dysfunction of the left ventricle, lowers its performance. The above phenomena are most pronounced in combination of IHD with severe AH. This combination presents a new qualitative state and, therefore, needs new approaches to its correction.


Integrative Analysis of Glucometabolic Traits, Adipose Tissue DNA Methylation, and Gene Expression Identifies Epigenetic Regulatory Mechanisms of Insulin Resistance and Obesity in African Americans.
Decline in insulin sensitivity due to dysfunction of adipose tissue (AT) is one of the earliest pathogenic events in type 2 diabetes. We hypothesize that differential DNA methylation (DNAm) controls insulin sensitivity and obesity by modulating transcript expression in AT. Integrating AT DNAm profiles with transcript profile data measured in a cohort of 230 African Americans (AAs) from the African American Genetics of Metabolism and Expression cohort, we performed cis-expression quantitative trait methylation (cis-eQTM) analysis to identify epigenetic regulatory loci for glucometabolic trait-associated transcripts. We identified significantly associated cytosine-guanine dinucleotide regions for 82 transcripts (false discovery rate [FDR]-P < 0.05). The strongest eQTM locus was observed for the proopiomelanocortin (POMC; ρ = -0.632, P = 4.70 × 10-27) gene. Epigenome-wide association studies (EWAS) further identified 155, 46, and 168 cytosine-guanine dinucleotide regions associated (FDR-P < 0.05) with the Matsuda index, SI, and BMI, respectively. Intersection of EWAS, transcript level to trait association, and eQTM results, followed by causal inference test identified significant eQTM loci for 23 genes that were also associated with Matsuda index, SI, and/or BMI in EWAS. These associated genes include FERMT3, ITGAM, ITGAX, and POMC In summary, applying an integrative multiomics approach, our study provides evidence for DNAm-mediated regulation of gene expression at both previously identified and novel loci for many key AT transcripts influencing insulin resistance and obesity.


Otolaryngologic manifestations of Down syndrome.
The DS patient has clear anatomic differences in the head and neck region when compared with the general population. These anomalies include a flat occiput, oblique palpebral fissures, epicanthal folds, speckled irides, a protruding tongue, prominent malformed ears, and a flat nasal bridge. Congenital otologic anomalies and acquired conditions such as otitis media are also more frequently observed in the DS population. The DS patient is predisposed to obstructive sleep apnea, and the diagnosis of sleep apnea in DS patients is more likely to be delayed. A child with DS who has a narrowed nasopharynx, large tongue, and a subglottis which is smaller than normal must be given special consideration at the time of intubation. Such a patient requires an endotracheal tube two sizes smaller than the standard size appropriate for the patient's age. The child should also be suspected of having and be evaluated for obstructive sleep apnea, to ensure that appropriate precautions are taken in the perioperative period. Finally, any DS patient undergoing preoperative evaluation for a general anesthetic should have a careful assessment of the cervical spine to avoid dislocation or spinal cord injury. Hearing loss may be suspected in any congenital syndrome. In DS, there is a clearly increased incidence of congenital temporal bone anomalies, external auditory canal stenosis, and otitis media. All DS patients should undergo hearing assessment in the neonatal period, with follow-up as appropriate. Aggressive treatment of conductive hearing loss and early amplification may be necessary to maximize speech and language development.


[Zellweger syndrome caused by PEX6 gene variation in 2 cases and literature review].
Objective: To summarize the clinical features and genetic characteristics of Zellweger spectrum disorder caused by PEX6 gene variation. Methods: This was a case series research. Clinical date and genetic results of 2 neonatal cases of Zellweger syndrome caused by PEX6 gene variation in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology and Affiliated Hospital of Guangdong Medical University from July 2021 to July 2022 were retrospectively collected and analyzed. Literature up to August 2023 was searched from electronic databases of China National Knowledge Infrastructure (CNKI), Wanfang Data and PubMed with the combined keywords of "Zellweger syndrome" "Zellweger spectrum disorder", and "PEX6 gene" both in Chinese and English. The main clinical features and genetic characteristics of Zellweger spectrum disorder caused by PEX6 gene variation were summarized. Results: The 2 male neonates both developed clinical manifestations as dyspnea, hypotonia, feeding difficulties, enlarged fontanelle, and high palatine arch after birth. Biochemical parameters indicated elevated bile acids, and the cranial ultrasound showed the enlarged bilateral ventricles and subependymal cyst in both 2 neonates. Zellweger syndrome was confirmed by whole exome sequencing, and the results revealed PEX6 gene variation in the 2 neonates, including compound heterozygous variants c.315G>A and c.2095-3T>G, and homozygous variant c.506_507del. Case 1 was hospitalized for 5 days, and case 2 for 32 days; they both died shortly after being discharged (the specific time is unknown). Literature review found 26 patients, including 2 neonates in this study, with Zellweger spectrum disorder caused by PEX6 gene defect reported in 1 Chinese article and 11 English articles. Clinical features included hearing loss (19 cases), developmental delay (19 cases), vision impairment (19 cases), elevated very long chain fatty acids (17 cases), brain malformations (15 cases), hypotonia (12 cases), hepatic insufficiency (12 cases), distinctive facies (10 cases), and dental impairment (9 cases). Compound heterozygous variations dominated the variation types (15 cases), and the frameshift variations (16 cases) were the main pathogenic variations. Conclusions: Zellweger spectrum disorder should be considered when neonates show hypotonia, feeding difficulty, distinctive facial appearance, brain malformations and failure of hearing screening, or when older children show retinitis pigmentosa, sensorineural hearing loss, amelogenesis imperfecta and developmental delays. Detection of genetic variation in the PEX gene is crucial for definitive diagnosis.


Murine pulmonary responses after sub-chronic exposure to aluminum oxide-based nanowhiskers.
Aluminum oxide-based nanowhiskers (AO nanowhiskers) have been used in manufacturing processes as catalyst supports, flame retardants, adsorbents, or in ceramic, metal and plastic composite materials. They are classified as high aspect ratio nanomaterials. Our aim was to assess in vivo toxicity of inhaled AO nanowhisker aerosols. Primary dimensions of AO nanowhiskers specified by manufacturer were 2-4 nm x 2800 nm. The aluminum content found in this nanomaterial was 30% [mixed phase material containing Al(OH)3 and AlOOH]. Male mice (C57Bl/6 J) were exposed to AO nanowhiskers for 4 hrs/day, 5 days/wk for 2 or 4 wks in a dynamic whole body exposure chamber. The whiskers were aerosolized with an acoustical dry aerosol generator that included a grounded metal elutriator and a venturi aspirator to enhance deagglomeration. Average concentration of aerosol in the chamber was 3.3 ± 0.6 mg/m3 and the mobility diameter was 150 ± 1.6 nm. Both groups of mice (2 or 4 wks exposure) were necropsied immediately after the last exposure. Aluminum content in the lung, heart, liver, and spleen was determined. Pulmonary toxicity assessment was performed by evaluation of bronchoalveolar lavage (BAL) fluid (enumeration of total and differential cells, total protein, activity of lactate dehydrogenase [LDH] and cytokines), blood (total and differential cell counts), lung histopathology and pulmonary mechanics. Following exposure, mean Al content of lungs was 0.25, 8.10 and 15.37 μg/g lung (dry wt) respectively for sham, 2 wk and 4 wk exposure groups. The number of total cells and macrophages in BAL fluid was 2-times higher in animals exposed for 2 wks and 6-times higher in mice exposed for 4 wks, compared to shams (p < 0.01, p < 0.001, respectively). However no neutrophilic inflammation in BAL fluid was found and neutrophils were below 1% in all groups. No significant differences were found in total protein, activity of LDH, or cytokines levels (IL-6, IFN-γ, MIP-1α, TNF-α, and MIP-2) between shams and exposed mice. Sub-chronic inhalation exposures to aluminum-oxide based nanowhiskers induced increased lung macrophages, but no inflammatory or toxic responses were observed.


A Prospective, Placebo-Controlled Pilot Evaluation of the Effect of Omeprazole on Serum Calcium, Magnesium, Cobalamin, Gastrin Concentrations, and Bone in Cats.
Chronic proton pump inhibitor administration has been associated with electrolyte and cobalamin deficiency, disrupted bone homeostasis, hypergastrinemia, and rebound acid hypersecretion in humans. It is unknown if this occurs in cats. Prolonged oral omeprazole results in altered bone mineral density or content, serum calcium, magnesium, cobalamin, and gastrin concentrations in healthy cats. Six healthy adult DSH cats. In a within subjects, before and after design, cats received placebo followed by omeprazole (0.83-1.6 mg/kg PO q12h) for 60 days each. Analysis of serum calcium, magnesium, cobalamin, and gastrin concentrations was performed on days 0, 30, and 60. Bone density and content were evaluated on days 0 and 60 of each intervention. Continuous data were analyzed using a two-way ANOVA (α = 0.006). On day 60 of omeprazole administration, continuous intragastric pH monitoring was performed in 2 cats to evaluate the effects of abrupt withdrawal of omeprazole. No significant changes were detected between treatments for any variables, except serum gastrin, which was significantly higher during omeprazole treatment in comparison to placebo (P = 0.002). Evidence of gastric hyperacidity was seen in both cats in which intragastric pH monitoring was performed following cessation of omeprazole. Although further studies with larger populations of cats will be needed to draw any definitive conclusions, these preliminary results suggest that prolonged PPI treatment results in hypergastrinemia and abrupt PPI withdrawal might result in RAH in cats.


Quantification of Trace Elements in Different Dokha and Shisha Tobacco Products using EDXRF.
The present study aims to quantify trace metals in different dokha (medwakh) and shisha tobacco products available in local markets. Recent research has shown that these products have higher amounts of nicotine and tar compared to various other tobacco products. No specific data are available on the concentration of trace elements in dokha (medwakh) and shisha tobacco products in the Middle East and North Africa (MENA) region. Harmful health effects due to the toxicity of these elements in tobacco and its smoke have not been adequately emphasized. Concentrations of trace elements were extensively studied using HORIBA XGT-7200 EDXRF fluorescence absorption spectroscopy. The mean concentrations of aluminum, calcium, chromium, copper, iron, magnesium, manganese, nickel, potassium, strontium and zinc in 13 dokha products in μg/g were 406.92 ± 41.72, 14703.27 ± 271.73, 11.73 ± 2.12, 25.58 ± 2.63, 753.85 ± 14.87, 5306.54 ± 134.94, 82.31 ± 4.55, 25.58 ± 2.50, 2212.12 ± 39.04, 816.92 ± 15.26 and 35.96 ± 2.63, respectively; and those in the three shisha products in μg/g were 244.83 ± 25.11, 8235.77 ± 144.51, 3.40 ± 0.38, 22.77 ± 4.50, 569.13 ± 10.22, 2096.20 ± 130.69, 72.13 ± 7.13, 27.67 ± 5.31, 4467.50 ± 168.06, 320.20 ± 6.03 and 36.40 ± 3.57, respectively. In our study, the quantified trace metal concentrations in dokha and shisha tobacco using the EDXRF method were ten times higher than the LODs. The percentage of RSD was <10%, validating the precision of the method. Tobacco smoking is a major source of consumption of toxic elements, not only in the smoker but also in non-smokers through passive smoking. In dokha (medwakh) and shisha tobacco products, compared with cigarettes, Ni levels were significantly higher, Cr, Cu and Zn levels were higher, and Fe levels were similar, while Al and Mn levels were lower. The dokha and shisha tobacco products have no filters; many toxic metals can quickly enter the lungs and cause different pulmonary diseases and oral infections. Tobacco smoking causes lung and oral cancers, chronic obstructive pulmonary disease and cardiovascular diseases.


Neglected microcystic adnexal carcinoma: the second reported case in a black patient.
Microcystic adnexal carcinoma (MAC) is a histologically aggressive appendageal neoplasm that often pursues a beguilingly indolent clinical course. MAC has previously been reported only once in a black patient. To present the second MAC ever recorded in a black patient. We describe a MAC of substantial dimension occurring in a black patient. The literature was subsequently examined for MAC occurring in ethnic patients. This MAC is remarkable not only for its occurrence in a black patient, but also because it is one of the largest MACs ever recorded (8 cm), it occurs in a relatively less common site (scalp), and its latency period before diagnosis is the longest ever definitively documented (31 years). MAC is rare among non-Caucasians. Its relatively indolent clinical growth, especially in sites that are poorly accessible to patient observation, may lead to significant delay in diagnosis and treatment.


[Family practitioner's and specialist's role in the care of the patient with epilepsy].
Differences of opinion between GPs and medical specialists about their roles in the care of patients with epilepsy make it difficult to improve this care. To assess the roles of GP and specialist care a random sample of 500 GPs and all clinical neurologists in The Netherlands were sent a questionnaire about their attitude and actual behaviour towards tasks concerning epilepsy. The response was 54%. Non-response analysis did not bring forward statistically significant differences. Both GPs and specialists considered further diagnosis and starting antiepileptic drug regimens tasks for the specialist. The treatment of attacks in the patient's home situation was considered by both groups as a task for the GP. About other tasks opinions were that they ought to be shared or opinions appeared to be divided. According to the authors tasks about which consensus exists as well as tasks about which opinions differ should be considered carefully: on management level by the Epilepsy consultation group of the Dutch Society of General Practitioners and the Dutch Epilepsy Federation, on care level by introducing a patient information card.


Effects of the precalving administration of omega-3 fatty acids alone or in combination with acetylsalicylic acid in periparturient dairy cows.
This study investigated the effects of the administration of long chain omega-3 fatty acids (ω-3 FA) and acetylsalicylic acid (ASA) on inflammation, performance, and fertility in periparturient dairy cows. Five weeks before calving, 26 multiparous dairy cows were randomly assigned to 1 of 3 treatments: ω-3 FA (n = 9; OME), ω-3 FA and ASA (n = 9; OMAS), or palm oil (n = 8; CTR). During the last 3 wk of pregnancy, OME and OMAS groups received daily 12.0 g of fish-derived ω-3 FA, whereas CTR cows received only SFA. In addition, OMAS cows received daily 6.0 mg ASA/kg BW starting at 7 d before calving. Only a few cows had health problems after calving, but those in OMAS were most affected (n = 3 vs. 1 in CTR). Inflammatory status around calving did not improve in OME cows, as confirmed by the patterns of concentration of acute-phase proteins (APP), which were similar to CTR. Compared with CTR and OME, the increase of the positive APP and the decrease of the negative APP (e.g., albumin; P < 0.01) observed in OMAS cows suggested a severe inflammatory status after calving. Compared with OMAS, postcalving energy metabolism was better in OME cows as shown by a lower degree of lipomobilization (smaller BCS drop, greater glucose) and milder ketogenesis (less β-hydroxybutyrate; P < 0.01). Cows in CTR had optimal fertility indices, whereas OMAS was the worst group. The severe inflammation and the more negative energy balance likely contributed to the poor fertility parameters in those cows. It is known that ASA exerts an inhibitory effect on cyclooxygenases, causing a possible decrease in the synthesis of PGF2α. A decreased concentration of PGF2α is connected with alterations in the physiologic processes related to labor and to uterine motility. Cows in OMAS had a longer pregnancy (P < 0.10 vs.OME) and a greater frequency of retained placenta, which may be attributed to decreased synthesis of PGF2α. The administration of ω-3 FA alone did not delay calving or the expulsion of fetal membranes. In conclusion, long-chain ω-3 FA improved the physiological status of cows, partly through better energy balance. The administration of ASA before calving (even at a low dose) in combination with ω-3 FA did not exert any synergistic positive effect on inflammation and performance.


Spousal associations of serum metabolomic profiles by nuclear magnetic resonance spectroscopy.
Phenotype-based assortative mating is well established in humans, with the potential for further convergence through a shared environment. To assess the correlation within infertile couples of physical, social, and behavioural characteristics and 155 circulating metabolic measures. Cross sectional study at a tertiary medical center of 326 couples undertaking IVF. Serum lipids, lipoprotein subclasses, and low-molecular weight metabolites as quantified by NMR spectroscopy (155 metabolic measures). Multivariable and quantile regression correlations within couples of metabolite profiles. Couples exhibited statistical correlations of varying strength for most physical, social, and behavioural characteristics including age, height, alcohol consumption, education, smoking status, physical activity, family history and ethnicity, with correlation coefficients ranging from 0.22 to 0.73. There was no evidence of within couple associations for BMI and weight, where the correlation coefficients were - 0.03 (95% CI - 0.14, 0.08) and 0.01 (95% CI - 0.10, 0.12), respectively. Within spousal associations of the metabolite measurements were all positive but with weak to modest magnitudes, with the median correlation coefficient across all 155 measures being 0.12 (range 0.01-0.37 and interquartile range 0.10-0.18). With just four having associations stronger than 0.3: docosahexaenoic acid (0.37, 95% CI 0.22, 0.52), omega-3 fatty acids (0.32, 95% CI 0.20, 0.43) histidine (0.32, 95% CI 0.23, 0.41) and pyruvate (0.32, 95% CI 0.22, 0.43). Infertile couples exhibit spousal similarities for a range of demographic and serum metabolite measures, supporting initial assortative mating, with diet-derived metabolites suggesting possible subsequent convergence of their individual metabolic profile.


Triple anterior screw fixation of an acute combination atlas-axis fracture. Case report.
The authors report the successful treatment of an acute combination atlas-axis fracture in an 85-year-old man using anterior odontoid and C1-2 transarticular facet screw fixation and a Philadelphia collar. Treatment with halo brace immobilization failed, and the patient experienced recurrent episodes of oxygen desaturation when placed partially prone for chest physiotherapy. If a posterior approach is not feasible, an anterior odontoid and C1-2 transarticular facet screw fixation can be considered as a salvage procedure for patients with acute combination atlas-axis fractures.


Retroviral insertions in Evi12, a novel common virus integration site upstream of Tra1/Grp94, frequently coincide with insertions in the gene encoding the peripheral cannabinoid receptor Cnr2.
The common virus integration site (VIS) Evi11 was recently identified within the gene encoding the hematopoietic G-protein-coupled peripheral cannabinoid receptor Cnr2 (also referred to as Cb2). Here we show that Cnr2 is a frequent target (12%) for insertion of Cas-Br-M murine leukemia virus (MuLV) in primary tumors in NIH/Swiss mice. Multiple provirus insertions in Evi11 were cloned and shown to be located within the 3' untranslated region of the candidate proto-oncogene Cnr2. These results suggest that proviral insertion in the Cnr2 gene is an important step in Cas-Br-M MuLV-induced leukemogenesis in NIH/Swiss mice. To isolate Evi11/Cnr2 collaborating proto-oncogenes, we searched for novel common VISs in the Cas-Br-M MuLV-induced primary tumors and identified a novel frequent common VIS, Evi12 (14%). Interestingly, 54% of the Evi11/Cnr2-rearranged primary tumors contained insertions in Evi12 as well, which suggests cooperative action of the target genes in these two common VISs in leukemogenesis. By interspecific backcross analysis it was shown that Evi12 resides on mouse chromosome 10 in a region that shares homology with human chromosomes 12q and 19p. Sequence analysis demonstrated that Evi12 is located upstream of the gene encoding the molecular chaperone Tra1/Grp94, which was previously mapped to mouse chromosome 10 and human chromosome 12q22-24. Thus, Tra1/Grp94 is a candidate target gene for retroviral activation or inactivation in Evi12. However, Northern and Western blot analyses did not provide evidence that proviral insertion had altered the expression of Tra1/Grp94. Additional studies are required to determine whether Tra1/Grp94 or another candidate proto-oncogene in Evi12 is involved in leukemogenesis.


The effect of apamin on the smooth muscle cells of the guinea-pig taenia coli.
The polypeptide apamin caused a small depolarization of the muscle cell membrane of the guinea-pig taenia coli accompanied by enhancement of spike activity and a concomitant muscle contration. The membrane hyperpolarization evoked by intramural stimulation of the non-adrenergic inhibitory nerves (inhibitory junction potential) was reduced by apamin; the antagonism being non-competitive in nature. The rebound depolarization and contraction following the inhibitory junction potential was enhanced by apamin. The membrane hyperpolarization induced by the purinergic compound ATP and by the sympathomimetic adrenaline was converted to a depolarization in the presence of apamin. This depolarization resulted in an increased spike activity and muscle contraction. This was followed by membrane hyperpolarization and muscle relaxation after washout of the drugs. These findings indicate that apamin is a non-competitive, non-specific antagonist of the non-adrenergic inhibitory transmitter and that the inhibitory junction potential and the rebound are mutually independent phenomena.


New mothers' experiences of social disruption and isolation during the severe acute respiratory syndrome outbreak in Hong Kong.
In Hong Kong during the severe acute respiratory syndrome outbreak of 2003, sustained uncertainty caused daily stress for residents for > 3 months. Expectant women experienced unexpected social disruption and isolation within their day-to-day life that have not been described in their own voice. The purpose of this study was to describe the experiences of women who became mothers during the outbreak and the ways in which these experiences impacted their early post-partum mothering. A phenomenological research design was chosen. The participants' responses then led the interview process. As the women's experiences had many similarities, saturation was reached after eight interviews. Four themes emerged: living with uncertainty, intense vigilance, isolation, and disrupted expectations. The participants spoke of disrupted daily routines as they tried to eliminate their risk of contracting this disease, including relationship difficulties with their spouse. None of the women had the birth experience they had hoped for because of changes in hospital practices.


Beta-conglycinin lowers very-low-density lipoprotein-triglyceride levels by increasing adiponectin and insulin sensitivity in rats.
The relationship between insulin sensitivity and the plasma triglyceride-lowering effect induced by beta-conglycinin was investigated. Male Wistar rats (19 weeks old) were fed diets containing casein, soy protein isolate, or beta-conglycinin for 4 weeks. In oral glucose administration, the beta-conglycinin-fed rats showed a significant decrease in the area under the glucose curve (0-60 min) as compared with the casein-fed rats. The hypoglycemic effect was significantly higher in the beta-conglycinin-fed rats than in the casein-fed rats at 30 min after intraperitoneal insulin injection. The liver sterol regulatory element-binding-protein-1 mRNA expression level was significantly lower and the plasma adiponectin concentration was significantly higher in the beta-conglycinin-fed rats than in the casein-fed rats. The hypotriglyceridemic effect of beta-conglycinin depended on a significant decrease in the concentration of very-low-density-lipoprotein triglycerides. These results indicate that beta-conglycinin increases adiponectin levels and improves glucose tolerance. The ability of beta-conglycinin to lower plasma lipid levels might be due to increased insulin sensitivity of the liver.


What can exome sequencing do for you?
Recent advances in next-generation sequencing technologies have brought a paradigm shift in how medical researchers investigate both rare and common human disorders. The ability cost-effectively to generate genome-wide sequencing data with deep coverage in a short time frame is replacing approaches that focus on specific regions for gene discovery and clinical testing. While whole genome sequencing remains prohibitively expensive for most applications, exome sequencing--a technique which focuses on only the protein-coding portion of the genome--places many advantages of the emerging technologies into researchers' hands. Recent successes using this technology have uncovered genetic defects with a limited number of probands regardless of shared genetic heritage, and are changing our approach to Mendelian disorders where soon all causative variants, genes and their relation to phenotype will be uncovered. The expectation is that, in the very near future, this technology will enable us to identify all the variants in an individual's personal genome and, in particular, clinically relevant alleles. Beyond this, whole genome sequencing is also expected to bring a major shift in clinical practice in terms of diagnosis and understanding of diseases, ultimately enabling personalised medicine based on one's genome. This paper provides an overview of the current and future use of next generation sequencing as it relates to whole exome sequencing in human disease by focusing on the technical capabilities, limitations and ethical issues associated with this technology in the field of genetics and human disease.


Real-time luminescence reporting of circadian gene expression in mammals.
Luminescence reporters have been used successfully in studies of circadian rhythms. Real-time measurements of circadian variations in gene expression were made in living cells, cultured tissues, and whole organisms. Because this technique is relatively easy and continuous noninvasive measurement from tissue cultures allows for a drastic reduction in the number of experimental animals, we believe this method will become a common technique for studying circadian rhythms. Using a multichannel recording apparatus, it may also become a powerful tool for the discovery of new drugs. In the past, measurements were done using hand-made apparatuses or by modifying commercially available equipment. We, along with other investigators, have developed user-friendly equipment for performing circadian rhythms experiments, and these systems are now available commercially. This article describes the use of luminescence reporters in circadian research and provides detailed methods used in these experiments. One of our goals in this article is to reduce experimental variability in different laboratories by proposing standard protocols.


Interactions of phagocytes with the Lyme disease spirochete: role of the Fc receptor.
The phagocytic capacity of murine and human mononuclear and polymorphonuclear phagocytes (including peripheral blood monocytes and neutrophils), rabbit and murine peritoneal exudate cells, and the murine macrophage cell line P388D1 against the Lyme disease spirochete was studied. All of these cells were capable of phagocytosing the spirochete; phagocytosis was measured by the uptake of radiolabeled spirochetes, the appearance of immunofluorescent bodies in phagocytic cells, and electron microscopy. Both opsonized and nonopsonized organisms were phagocytosed. The uptake of opsonized organisms by neutrophils was blocked by a monoclonal antibody specific for the Fc receptor and by immune complexes; these findings suggested that most phagocytosis is mediated by the Fc receptor. Similarly, the uptake of opsonized organisms by human monocytes was inhibited by human monomeric IgG1 and by immune complexes. These results illustrate the role of immune phagocytosis of spirochetes in host defense against Lyme disease.


Intracrystalline diffusion in mesoporous zeolites.
Specially synthesized extra-large crystallites of zeolite LTA with intentionally added mesoporosity are used for an in-depth study of guest diffusion in hierarchical nanoporous materials by the pulsed field gradient NMR technique. Using propane as a guest molecule, intracrystalline mass transfer is demonstrated to be adequately described by a single effective diffusivity resulting from the weighted average of the diffusivities in the two (micro- and meso-) pore spaces. Gas-kinetic order-of-magnitude estimates of the diffusivities are in satisfactory agreement with the experimental data and are thus shown to provide a straightforward means for predicting and quantifying the benefit of hierarchically structured nanoporous materials in comparison with their purely microporous equivalent.


Rates of late cenozoic uplift, baldwin hills, los angeles, california.
Radiocarbon ages for the marine late Pleistocene stratigraphic units of the Baldwin Hills are 36,200 +/- 2,750 years and 28,450 +/- 2,600 years, respectively, defining the termination of marine deposition in this area of the Los Angeles Basin at less than 28,000 years ago. Faunas of the older sample suggest that water depths were about 100 meters at the time of deposition. Shoaling of waters by deposition resulted in very shallow marine to nonmarine conditions about 28,000 years ago. The average rates of uplift for the past 36,000 years have been between 0.5 and 0.8 meter per 100 years.


Clinical efficiency and reusability of the reciprocating nickel-titanium instruments according to the root canal anatomy.
The application of the single-file technique using the reciprocating motion is gaining concern in root canal preparation. The purpose of this research is to compare the efficiency of the reciprocating motion-employing files (RECIPROC and WaveOne) by measuring the working time for complete canal shaping, and to evaluate their reusability under scanning examinations. One hundred curved root canals of the extracted molars were used. The working length was determined and the glide path was confirmed using a #15 K-file. Canals shaping was completed to the length either with RECIPROC R25 file (n = 50), or with WaveOne Primary file (n = 50). The time taken for the file to reach the working length was also measured. Each file was repeatedly used in a maximum of 10 canals for comparing the change of the efficiency (shaping time) according to the working length, canal curvature, and number of file re-use. The deformations or surface defects of the files after the in vitro use were observed using a scanning electron microscope (SEM). There was no difference under the SEM between the 2 file groups with no initiation of micro-cracks until they were re-used up to 5 canals. WaveOne Primary file showed significantly shorter working time than RECIPROC R25 (p < 0.05). There was a statistically significant correlation between the working time and three variables. As the working length and the curvature of the canal increased, the shaping time was increased in both file systems. Reusability of these reciprocating instruments might be maximum 5 canals with minimal surface deformations.


Back-to-school upper respiratory infection in preschool and primary school-age children in Israel.
Increased upper respiratory infection (URI) among children at the beginning of school year is well known to parents and pediatricians. However, this phenomenon is not well documented or characterized. Computerized datasets from a large health maintenance organization in Israel were used to calculate the weekly rates of URI among children 3-14 years old for the years 2007-2012. In addition, nasopharyngeal swabs were collected in 2010-2012 from children with URI symptoms and controls during school opening time. Swabs were tested by real-time polymerase chain reaction for the presence of respiratory viruses. Time-series analysis demonstrated a peak of URI in September each year. The peaks reached their height 2 weeks after school opening and returned to baseline within 4-7 weeks. The main 3 viruses detected both in URI patients and in healthy controls during the first weeks of school opening were rhinovirus, adenovirus and enterovirus. The detection rate of any respiratory virus, and of rhinovirus in particular, was significantly higher among cases than among controls (54% vs. 16%, P < 0.001 for any virus, and 35% vs. 6.0%, P < 0.01 for rhinovirus). When adjusting for age and sex cases had 5.8 times more viral detection when compared with controls. Upper respiratory symptoms were significantly more prevalent among the virus-positive cases when compared with negative ones. Back-to-school illness consisting of URI has a distinct epidemiological pattern demonstrating a rapid rise peaking within 2 weeks of school opening and is associated predominantly with rhinovirus.


The inter-rater reliability of the Risk Instrument for Screening in the Community.
Predicting risk of adverse healthcare outcomes is important to enable targeted delivery of interventions. The Risk Instrument for Screening in the Community (RISC), designed for use by public health nurses (PHNs), measures the 1-year risk of hospitalisation, institutionalisation and death in community-dwelling older adults according to a five-point global risk score: from low (score 1,2) to medium (3) to high (4,5). We examined the inter-rater reliability (IRR) of the RISC between student PHNs (n=32) and expert raters using six cases (two low, medium and high-risk), scored before and after RISC training. Correlations increased for each adverse outcome, statistically significantly for institutionalisation (r=0.72 to 0.80, p=0.04) and hospitalisation (r=0.51 to 0.71, p<0.01) but not death. Training improved accuracy for low-risk but not all high-risk cases. Overall, the RISC showed good IRR, which increased after RISC training. That reliability fell for some high-risk cases suggests that the training programme requires adjustment to improve IRR further.


Effect of carbon black exposure on respiratory function and symptoms.
Carbon black is a widely used pigment and filler. Some, but not all, previous studies have suggested an effect of long-term exposure upon the lungs. Carbon black production facility employees (1755) participated in the third round of the industry-wide medical surveillance testing. They were employed in 22 North American plants. Spirometry and a systematically administered questionnaire were included in the year 2000 round of the industry-wide medical surveillance program. Industrial hygiene data from an industry-wide survey in 2000-2001, as well as all available exposure assessment data collected since 1979, were integrated with process questionnaires and exposure rating questionnaires completed by plant personnel. Analyses included multiple linear regression and categorical data analyses. Multiple regression analyses showed statistically significant, consistent relationships between cumulative exposure and small reductions in forced expiratory volume in 1 second (FEV1) but not with other spirometry parameters. The estimated slopes were -2 mL FEV1 per mg-year/m3 of cumulative 'total' dust exposure and -0.7 mL FEV1 per mg-year/m3 of cumulative exposure for the inhalable fraction. In addition, heavy cumulative exposures were associated with a small increase in chronic bronchitis in nonsmokers. Recent exposures, typically much lower than in the past, were not demonstrated to be associated with these effects. Consistent with good occupational hygiene practice for any contaminant, workplace exposures to carbon black should be controlled to lowest practical levels.


Rapid 3D printing of anatomically accurate and mechanically heterogeneous aortic valve hydrogel scaffolds.
The aortic valve exhibits complex three-dimensional (3D) anatomy and heterogeneity essential for the long-term efficient biomechanical function. These are, however, challenging to mimic in de novo engineered living tissue valve strategies. We present a novel simultaneous 3D printing/photocrosslinking technique for rapidly engineering complex, heterogeneous aortic valve scaffolds. Native anatomic and axisymmetric aortic valve geometries (root wall and tri-leaflets) with 12-22 mm inner diameters (ID) were 3D printed with poly-ethylene glycol-diacrylate (PEG-DA) hydrogels (700 or 8000 MW) supplemented with alginate. 3D printing geometric accuracy was quantified and compared using Micro-CT. Porcine aortic valve interstitial cells (PAVIC) seeded scaffolds were cultured for up to 21 days. Results showed that blended PEG-DA scaffolds could achieve over tenfold range in elastic modulus (5.3±0.9 to 74.6±1.5 kPa). 3D printing times for valve conduits with mechanically contrasting hydrogels were optimized to 14 to 45 min, increasing linearly with conduit diameter. Larger printed valves had greater shape fidelity (93.3±2.6, 85.1±2.0 and 73.3±5.2% for 22, 17 and 12 mm ID porcine valves; 89.1±4.0, 84.1±5.6 and 66.6±5.2% for simplified valves). PAVIC seeded scaffolds maintained near 100% viability over 21 days. These results demonstrate that 3D hydrogel printing with controlled photocrosslinking can rapidly fabricate anatomical heterogeneous valve conduits that support cell engraftment.


A Competing-Risk Approach for Modeling Length of Stay in Severe Malaria Patients in South-East Asia and the Implications for Planning of Hospital Services.
Management of severe malaria with limited resources requires comprehensive planning. Expected length of stay (LOS) and the factors influencing it are useful in the planning and optimisation of service delivery. A secondary, competing-risk approach to survival analysis was performed for 1217 adult severe malaria patients from the South-East Asia Quinine Artesunate Malaria Trial. Twenty percent of patients died; 95.4% within 7 days compared to 70.3% of those who were discharged. Median time to discharge was 6 days. Compared to quinine, artesunate increased discharge incidence (subdistribution-Hazard ratio, 1.24; [95% confidence interval 1.09-1.40]; P = .001) and decreased incidence of death (0.60; [0.46-0.80]; P < .001). Low Glasgow coma scale (discharge, 1.08 [1.06-1.11], P < .001; death, 0.85 [0.82-0.89], P < .001), high blood urea-nitrogen (discharge, 0.99 [0.99-0.995], P < .001; death, 1.00 [1.00-1.01], P = .012), acidotic base-excess (discharge, 1.05 [1.03-1.06], P < .001; death, 0.90 [0.88-0.93], P < .001), and development of shock (discharge, 0.25 [0.13-0.47], P < .001; death, 2.14 [1.46-3.12], P < .001), or coma (discharge, 0.46 [0.32-0.65], P < .001; death, 2.30 [1.58-3.36], P < .001) decreased cumulative incidence of discharge and increased incidence of death. Conventional Kaplan-Meier survival analysis overestimated cumulative incidence compared to competing-risk model. Clinical factors on admission and during hospitalisation influence LOS in severe malaria, presenting targets to improve health and service efficiency. Artesunate has the potential to increase LOS, which should be accounted for when planning services. In-hospital death is a competing risk for discharge; an important consideration in LOS models to reduce overestimation of risk and misrepresentation of associations.


Temporal Dynamics of Corticomuscular Coherence Reflects Alteration of the Central Mechanisms of Neural Motor Control in Post-Stroke Patients.
The neural control of muscular activity during a voluntary movement implies a continuous updating of a mix of afferent and efferent information. Corticomuscular coherence (CMC) is a powerful tool to explore the interactions between the motor cortex and the muscles involved in movement realization. The comparison of the temporal dynamics of CMC between healthy subjects and post-stroke patients could provide new insights into the question of how agonist and antagonist muscles are controlled related to motor performance during active voluntary movements. We recorded scalp electroencephalography activity, electromyography signals from agonist and antagonist muscles, and upper limb kinematics in eight healthy subjects and seventeen chronic post-stroke patients during twenty repeated voluntary elbow extensions and explored whether the modulation of the temporal dynamics of CMC could contribute to motor function impairment. Concomitantly with the alteration of elbow extension kinematics in post-stroke patients, dynamic CMC analysis showed a continuous CMC in both agonist and antagonist muscles during movement and highlighted that instantaneous CMC in antagonist muscles was higher for post-stroke patients compared to controls during the acceleration phase of elbow extension movement. In relation to motor control theories, our findings suggest that CMC could be involved in the online control of voluntary movement through the continuous integration of sensorimotor information. Moreover, specific alterations of CMC in antagonist muscles could reflect central command alterations of the selectivity in post-stroke patients.


Gluten sensitive enteropathy in patients with iron deficiency anemia of unknown origin.
To determine the prevalence of gluten sensitive enteropathy (GSE) in a large group of patients with iron deficiency anemia (IDA) of obscure origin. In this cross-sectional study, patients with IDA of obscure origin were screened for GSE. Anti-endomysial antibody (EMA) and tissue transglutaminase antibody (tTG) levels were evaluated and duodenal biopsies were taken and scored according to the Marsh classification. The diagnosis of GSE was based on a positive serological test and abnormal duodenal histology. Gluten free diet (GFD) was advised for all the GSE patients. Of the 4120 IDA patients referred to our Hematology departments, 206 (95 male) patients were found to have IDA of obscure origin. Thirty out of 206 patients (14.6%) had GSE. The mean age of GSE patients was 34.6 +/- 17.03 (range 10-72 years). The female to male ratio was 1.3:1. Sixteen patients had Marsh 3, 12 had Marsh 2, and 2 had Marsh 1 lesions. The severity of anemia was in parallel with the severity of duodenal lesions. Twenty-two GSE patients (73.3%) had no gastrointestinal symptoms. Fourteen GSE patients who adhered to GFD without receiving iron supplementation agreed to undergo follow up visits. After 6 mo of GFD, their mean hemoglobin levels (Hb) increased from 9.9 +/- 1.6 to 12.8 +/- 1.0 g/dL (P < 0.01). Interestingly, in 6 out of 14 patients who had Marsh 1/2 lesions (e.g. no villous atrophy) on duodenal biopsy, mean Hb increased from 11.0 +/- 1.1 to 13.1 +/- 1.0 g/dL (P < 0.01) while they did not receive any iron supplementation. There is a high prevalence (e.g. 14.6%) of GSE in patients with IDA of obscure origin. Gluten free diet can improve anemia in GSE patients who have mild duodenal lesions without villous atrophy.


Neurological manifestations associated with COVID-19: a review and a call for action.
While the epidemic of Coronavirus disease 2019 (COVID-19) continues to spread globally, more and more evidences are collected about the presence of neurological manifestations and symptoms associated with it. A systematic review has been performed of papers published until 5 April 2020. 29 papers related to neurological manifestations associated with COVID-19 were examined. The results show presence of central and peripheral nervous system manifestations related to coronavirus. Neurological manifestations, or NeuroCOVID, are part of the COVID-19 clinical picture, but questions remain regarding the frequency and severity of CNS symptoms, the mechanism of action underlying neurological symptoms, and the relationship of symptoms with the course and severity of COVID-19. Further clinical, epidemiological, and basic science research is urgently needed to understand and address neurological sequalae of COVID-19. Concomitant risk factors or determinants (e.g. demographic factors, comorbidities, or available biomarkers) that may predispose a person with COVID-19 to neurological manifestations also need to be identified. The review shows that although more and more papers are reporting neurological manifestations associated with COVID-19; however, many items remain unclear and this uncertainty calls for a global action that requires close coordination and open-data sharing between hospitals, academic institutions and the fast establishment of harmonised research priorities and research consortia to face the NeuroCOVID-19 complications.


Significance of telomere capture in myelodysplastic syndromes.
Addition of telomeres to the ends of broken chromosomes has been observed in many malignant cells through the capture of the ends of other chromosomes as a result of nonreciprocal translocations. In this study, we aimed to evaluate the percentage of nuclei with telomere capture (TC%) as a prognostic marker in myelodysplastic syndromes (MDS) patients. This study included 45 newly diagnosed MDS patients, 36 cases with denovo MDS and 9 cases with therapy-related MDS, and another 35 apparently healthy volunteers as a control group. Telomere capture percentage was investigated with fluorescent in situ hybridization technique using a probe for 15qter. We found that median TC% rate was significantly increased in those with bad cytogenetic abnormalities, patients with blast cells>10% in BM, and patients categorized as high risk according to WHO and IPSS classification; also, there was a significant negative correlation with progression-free survival. Telomere capture serves as a useful marker for the assessment of MDS patient's risk, and also it had a clinical importance for the early detection of disease progression.


Analyzing Particularities of Sensor Datasets for Supporting Data Understanding and Preparation.
Data scientists spend much time with data cleaning tasks, and this is especially important when dealing with data gathered from sensors, as finding failures is not unusual (there is an abundance of research on anomaly detection in sensor data). This work analyzes several aspects of the data generated by different sensor types to understand particularities in the data, linking them with existing data mining methodologies. Using data from different sources, this work analyzes how the type of sensor used and its measurement units have an important impact in basic statistics such as variance and mean, because of the statistical distributions of the datasets. The work also analyzes the behavior of outliers, how to detect them, and how they affect the equivalence of sensors, as equivalence is used in many solutions for identifying anomalies. Based on the previous results, the article presents guidance on how to deal with data coming from sensors, in order to understand the characteristics of sensor datasets, and proposes a parallelized implementation. Finally, the article shows that the proposed decision-making processes work well with a new type of sensor and that parallelizing with several cores enables calculations to be executed up to four times faster.


Antimalarials as Antivirals for COVID-19: Believe it or Not!
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus responsible for the coronavirus disease -19 (COVID-19). Since December 2019, SARS-CoV-2 has infected millions of people worldwide, leaving hundreds of thousands dead. Chloroquine (CQ) and Hydroxychloroquine (HCQ) are antimalarial medications that have been found to have in vitro efficacy against SARS-CoV-2. Several small prospective studies have shown positive outcomes. However, this result has not been universal, and concerns have been raised regarding the indiscriminate use and potential side effects. The clinicians are conflicted regarding the usage of these medications. Appropriate dose and duration of therapy are unknown. Here, we will discuss the pharmacokinetic and pharmacodynamic properties of CQ and HCQ, as well as review the antiviral properties. The manuscript will also examine the available data from recent clinical and preclinical trials in order to shed light on the apparent inconsistencies.


Rampant centrosome amplification underlies more aggressive disease course of triple negative breast cancers.
Centrosome amplification (CA), a cell-biological trait, characterizes pre-neoplastic and pre-invasive lesions and is associated with tumor aggressiveness. Recent studies suggest that CA leads to malignant transformation and promotes invasion in mammary epithelial cells. Triple negative breast cancer (TNBC), a histologically-aggressive subtype shows high recurrence, metastases, and mortality rates. Since TNBC and non-TNBC follow variable kinetics of metastatic progression, they constitute a novel test bed to explore if severity and nature of CA can distinguish them apart. We quantitatively assessed structural and numerical centrosomal aberrations for each patient sample in a large-cohort of grade-matched TNBC (n = 30) and non-TNBC (n = 98) cases employing multi-color confocal imaging. Our data establish differences in incidence and severity of CA between TNBC and non-TNBC cell lines and clinical specimens. We found strong correlation between CA and aggressiveness markers associated with metastasis in 20 pairs of grade-matched TNBC and non-TNBC specimens (p < 0.02). Time-lapse imaging of MDA-MB-231 cells harboring amplified centrosomes demonstrated enhanced migratory ability. Our study bridges a vital knowledge gap by pinpointing that CA underlies breast cancer aggressiveness. This previously unrecognized organellar inequality at the centrosome level may allow early-risk prediction and explain higher tumor aggressiveness and mortality rates in TNBC patients.


Stakeholder feedback on The CARD™ System to improve the vaccination experience at school.
School-based vaccination programs can be a source of distress for many students due to the pain from the needle injection and related fears. We created a multifaceted Knowledge Translation (KT) intervention to address vaccination and pain, fear, and fainting called The CARD™ System. The objectives were to document acceptability of key tools included in the multifaceted KT intervention and their effectiveness in improving knowledge and attitudes about vaccination pain and fear. Quantitative and qualitative methods were used. Students, school staff, public health nurses, and parents participated in separate focus groups whereby they independently completed a knowledge and attitudes survey and provided structured and qualitative feedback on key KT tools of the multifaceted KT intervention. They then repeated the knowledge and attitudes survey. Altogether, 22 students (grade 6 and 7), 16 school staff (principals, grade 7 and 8 teachers, resource teachers, secretaries), 10 nurses (injecting, charge, and school nurses), and 3 parents participated. Knowledge test scores increased post-KT tool review: 8.5 (2.1) versus 7.3 (1.9); P<0.001. Attitudes were more positive about the individual nature of pain and fear experience during vaccination. Student fear scores were lower post-tool review: 5.1 (2.9) versus 4.6 (3.0); P<0.001. The majority of the participants reported they understood all the information, the amount was just right and that the information was useful. The KT tools were demonstrated to be acceptable and to improve knowledge. Future research is warranted to determine their impact on student experience during school vaccinations.


Why did she leave? Development of working alliance in a case of psychotherapy for depression.
The present case study aims to explore the unfolding of the working alliance in a case that ended with the client dropping out of psychotherapy, unilaterally cutting off her contact with the therapist. However, both quantitative and qualitative outcome assessments strongly suggested that. An analysis of session transcripts, the Client Change Interview, and the Interpersonal Process Recall interviews for three selected sessions was used to analyze the development of the working alliance and its contribution to the dropout. This case study illustrates how the working alliance is constructed differently during the different phases of the therapeutic process. Specifically, the fruitful problem-solving in the first part of psychotherapy helped the client to improve her functioning. Yet this intervention seemed to exhaust its potential over time, and later the dyad had trouble finding another useful mode of interaction due to the interpersonal context, leading to more serious ruptures and, eventually, to the dropout. The findings are discussed in terms of therapist responsiveness and of its role in the continuous negotiation of the working alliance.


The cranial base of Australopithecus afarensis: new insights from the female skull.
Cranial base morphology differs among hominoids in ways that are usually attributed to some combination of an enlarged brain, retracted face and upright locomotion in humans. The human foramen magnum is anteriorly inclined and, with the occipital condyles, is forwardly located on a broad, short and flexed basicranium; the petrous elements are coronally rotated; the glenoid region is topographically complex; the nuchal lines are low; and the nuchal plane is horizontal. Australopithecus afarensis (3.7-3.0 Ma) is the earliest known species of the australopith grade in which the adult cranial base can be assessed comprehensively. This region of the adult skull was known from fragments in the 1970s, but renewed fieldwork beginning in the 1990s at the Hadar site, Ethiopia (3.4-3.0 Ma), recovered two nearly complete crania and major portions of a third, each associated with a mandible. These new specimens confirm that in small-brained, bipedal Australopithecus the foramen magnum and occipital condyles were anteriorly sited, as in humans, but without the foramen's forward inclination. In the large male A.L. 444-2 this is associated with a short basal axis, a bilateral expansion of the base, and an inferiorly rotated, flexed occipital squama--all derived characters shared by later australopiths and humans. However, in A.L. 822-1 (a female) a more primitive morphology is present: although the foramen and condyles reside anteriorly on a short base, the nuchal lines are very high, the nuchal plane is very steep, and the base is as relatively narrow centrally. A.L. 822-1 illuminates fragmentary specimens in the 1970s Hadar collection that hint at aspects of this primitive suite, suggesting that it is a common pattern in the A. afarensis hypodigm. We explore the implications of these specimens for sexual dimorphism and evolutionary scenarios of functional integration in the hominin cranial base.


On the growth and microstructure of carbon nanotubes grown by thermal chemical vapor deposition.
Carbon nanotubes (CNTs) were deposited on various substrates namely untreated silicon and quartz, Fe-deposited silicon and quartz, HF-treated silicon, silicon nitride-deposited silicon, copper foil, and stainless steel mesh using thermal chemical vapor deposition technique. The optimum parameters for the growth and the microstructure of the synthesized CNTs on these substrates are described. The results show that the growth of CNTs is strongly influenced by the substrate used. Vertically aligned multi-walled CNTs were found on quartz, Fe-deposited silicon and quartz, untreated silicon, and on silicon nitride-deposited silicon substrates. On the other hand, spaghetti-type growth was observed on stainless steel mesh, and no CNT growth was observed on HF-treated silicon and copper. Silicon nitride-deposited silicon substrate proved to be a promising substrate for long vertically aligned CNTs of length 110-130 μm. We present a possible growth mechanism for vertically aligned and spaghetti-type growth of CNTs based on these results.


Association analysis of GSTT1, GSTM1 genotype polymorphisms and serum total GST activity with ischemic stroke risk.
Oxidative stress plays a major role in pathogenesis of atherosclerosis which is responsible for stroke. Glutathione S-transferases (GSTs) detoxify metabolites produced by oxidative stress within the cell and protect the cells against injury. This study aimed to investigate the association of polymorphisms in GSTT1, GSTM1 genes and GST activity with ischemic stroke risk. Patients had almost the same GST activity as that of controls. No significant differences were found between patients and controls in terms of GSTT1 null, GSTM1 null and GSTT1/GSTM1 double null genotype frequencies. Besides, both patients and controls with double GSTT1/GSTM1 null genotypes had the lowest serum GST activities. Compared to the present genotypes, GSTT1 null (OR = 4.888; P = 0.006) and GSTM1 null (OR = 2.383; P = 0.011) genotype groups contained relatively more hypertensive stroke patients. This study showed that GSTT1 and GSTM1 null genotypes, together with hypertension, may play a significant role in the pathogenesis of ischemic stroke.


Automated screening system for retinal health using bi-dimensional empirical mode decomposition and integrated index.
Posterior Segment Eye Diseases (PSED) namely Diabetic Retinopathy (DR), glaucoma and Age-related Macular Degeneration (AMD) are the prime causes of vision loss globally. Vision loss can be prevented, if these diseases are detected at an early stage. Structural abnormalities such as changes in cup-to-disc ratio, Hard Exudates (HE), drusen, Microaneurysms (MA), Cotton Wool Spots (CWS), Haemorrhages (HA), Geographic Atrophy (GA) and Choroidal Neovascularization (CNV) in PSED can be identified by manual examination of fundus images by clinicians. However, manual screening is labour-intensive, tiresome and time consuming. Hence, there is a need to automate the eye screening. In this work Bi-dimensional Empirical Mode Decomposition (BEMD) technique is used to decompose fundus images into 2D Intrinsic Mode Functions (IMFs) to capture variations in the pixels due to morphological changes. Further, various entropy namely Renyi, Fuzzy, Shannon, Vajda, Kapur and Yager and energy features are extracted from IMFs. These extracted features are ranked using Chernoff Bound and Bhattacharyya Distance (CBBD), Kullback-Leibler Divergence (KLD), Fuzzy-minimum Redundancy Maximum Relevance (FmRMR), Wilcoxon, Receiver Operating Characteristics Curve (ROC) and t-test methods. Further, these ranked features are fed to Support Vector Machine (SVM) classifier to classify normal and abnormal (DR, AMD and glaucoma) classes. The performance of the proposed eye screening system is evaluated using 800 (Normal=400 and Abnormal=400) digital fundus images and 10-fold cross validation method. Our proposed system automatically identifies normal and abnormal classes with an average accuracy of 88.63%, sensitivity of 86.25% and specificity of 91% using 17 optimal features ranked using CBBD and SVM-Radial Basis Function (RBF) classifier. Moreover, a novel Retinal Risk Index (RRI) is developed using two significant features to distinguish two classes using single number. Such a system helps to reduce eye screening time in polyclinics or community-based mass screening. They will refer the patients to main hospitals only if the diagnosis belong to the abnormal class. Hence, the main hospitals will not be unnecessarily crowded and doctors can devote their time for other urgent cases.


Data-driven analysis to understand long COVID using electronic health records from the RECOVER initiative.
Recent studies have investigated post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID) using real-world patient data such as electronic health records (EHR). Prior studies have typically been conducted on patient cohorts with specific patient populations which makes their generalizability unclear. This study aims to characterize PASC using the EHR data warehouses from two large Patient-Centered Clinical Research Networks (PCORnet), INSIGHT and OneFlorida+, which include 11 million patients in New York City (NYC) area and 16.8 million patients in Florida respectively. With a high-throughput screening pipeline based on propensity score and inverse probability of treatment weighting, we identified a broad list of diagnoses and medications which exhibited significantly higher incidence risk for patients 30-180 days after the laboratory-confirmed SARS-CoV-2 infection compared to non-infected patients. We identified more PASC diagnoses in NYC than in Florida regarding our screening criteria, and conditions including dementia, hair loss, pressure ulcers, pulmonary fibrosis, dyspnea, pulmonary embolism, chest pain, abnormal heartbeat, malaise, and fatigue, were replicated across both cohorts. Our analyses highlight potentially heterogeneous risks of PASC in different populations.


A microcomputer program for comparison and alignment of DNA sequence gel readings.
During the course of determining the sequence of a large DNA fragment, it is necessary to cross-check numerous gel readings from different DNA fragments, in order to track and eliminate mistakes. An algorithm is presented that takes advantage of the high degree of homology between such sequences to construct an alignment of the matching regions. It does not require knowledge of a starting homology zone, neither large memory areas, even for sequences of several kilobases, and it can overcome large gaps or mismatch zones that correspond for instance to misinterpretation of compressions on sequence gels. This algorithm has been implemented in 6502 assembly language on an Apple II computer as an extension to the PEGASE sequence handling system.


Multiple positive and negative regulatory elements in the promoter of the mouse homeobox gene Hoxb-4.
Mouse Hoxb-4 (Hox-2.6) is a homeobox gene that belongs to a family which also includes Hoxa-4, Hoxc-4, and Hoxd-4 and that is related to the Deformed gene in Drosophila melanogaster. We have determined the sequence of 1.2 kb of 5' flanking DNA of mouse Hoxb-4 and by nuclease S1 and primer extension experiments identified two transcription start sites, P1 and P2, 285 and 207 nucleotides upstream of the ATG initiator codon, respectively. We have shown that this region harbors two independent promoters which drive CAT expression in several different cell lines with various efficiencies, suggesting that they are subject to cell-type-specific regulation. Through detailed mutational analysis, we have identified several cis-regulatory elements, located upstream and downstream of the transcription start sites. They include two cell-type-specific negative regulatory elements, which are more active in F9 embryonal carcinoma cells than in neuroblastoma cells (regions a and d at -226 to -186 and +169 to +205, respectively). An additional negative regulatory element has been delimited (region b between +22 and +113). Positive regulation is achieved by binding of HoxTF, a previously unknown factor, to the sequence GCCATTGG (+148 to +155) that is essential for efficient Hoxb-4 expression. We have also defined the minimal promoter sequences and found that they include two 12-bp initiator elements centered around each transcription start site. The complex architecture of the Hoxb-4 promoter provides the framework for fine-tuned transcriptional regulation during embryonic development.


Diffraction-limited imaging through a phase-distorting medium.
An achromatic method of seeing through a phase-distorting medium, such as a turbulent atmosphere, utilizes a grating interferometer. Measurements are made at sample points throughout the region of fringe formation. A set of nonlinear simultaneous equations is generated and then solved by computer.


'Progressive diabetic nephropathy. How useful is microalbuminuria?: contra'.
The concept of microalbuminuria has been central to the development of clinical practice and research in the area of diabetic kidney disease (DKD). However, in recent times, the value of a paradigm of DKD based solely on microalbuminuria has been questioned. Although both the absolute level and rate of change of microalbuminuria are linked to the development and progression of DKD, microalbuminuria on its own lacks the necessary sensitivity or specificity to accurately predict kidney outcomes for people with diabetes. The development of microalbumiuria can no longer be viewed as a committed and irreversible stage of DKD, as spontaneous remission is now reported as a common occurrence. In addition, the absence of microalbuminuria or its progression to proteinuria does not signify that an individual patient is safe from a progressive decline in glomerular filtration rate (GFR). Furthermore, although reductions in albuminuria within the microalbuminuric range can be linked to a slower GFR decline in observational studies, this relationship has not been robustly demonstrated in intervention studies. Conclusions regarding the kidney health of individuals with diabetes will continue to be flawed if an inappropriate emphasis is placed on the presence or absence of albuminuria or changes in albuminuria within the microalbuminuric range. This has important implications in terms of undermining the value of microalbuminuria as a surrogate renal end point for intervention trials. There is a need to develop broader models of progressive DKD that include novel pathways and risk markers apart from those related to the traditional 'albuminuric pathway' to renal impairment.


Efficacy and safety of bimatoprost in patients with uncontrolled glaucoma as alternative to filtration surgery.
To evaluate the efficacy and safety of bimatoprost 0.03% as an alternative to filtration surgery in patients with uncontrolled glaucoma. Interventional study. A total of 83 consecutive patients (83 eyes) awaiting glaucoma surgery were enrolled in eight ophthalmic centers. Reasons for listing were inadequate intraocular pressure (IOP) control despite medical therapy and documented progression of visual field loss. All patients discontinued the previous treatment and were switched to bimatoprost 0.03% QD (one drop at 9 pm). The primary efficacy outcome was a 20% IOP reduction from baseline at each timepoint. IOP was measured at day 7, day 30, day 60, and day 90 of treatment; less than 20% IOP reduction was considered as a failure. An IOP reduction of at least 20% was achieved in 74 patients (89.1%) after 7 days and in 64 patients (86.5%) after 30 days. Sixty-two patients (74.6%) maintained IOP readings 20% lower than baseline after 60 and 90 days. In these patients, visual field indices improved in 8 eyes (13%), and remained unchanged in 54 eyes (87%). Ocular side effects were conjunctival injection (15.6%), burning sensation (9.6%), foreign body sensation (4.8%), and eyelash growth (2.4%). This preliminary study shows that bimatoprost 0.03% could represent a useful therapeutic tool that might defer filtration surgery.


Testing a model for excimer laser-ablation rates on corneal shape after refractive surgery.
We have tested whether a recent model [Appl. Phys. Lett.95, 174105 (2009)APPLAB0003-695110.1063/1.3254236] that considers the angular dependence of laser-ablation rates, including reflection losses and geometrical dependence of incident fluence, and the effect of plume absorption can have significant effects for refractive surgery patients. We have developed a mathematical procedure and deduced equations that show that this model can significantly influence postsurgical corneal parameters (radius and asphericity) and, thus, should be considered in ablation algorithms in order to achieve a better emmetropization and an effective correction of eye aberrations.


Promotion of breast-feeding in a Chinese community in Montreal.
Following a prospective survey that showed a very low rate of breast-feeding (10%) in 1977-79 among Chinese women in Montreal, a culturally targeted program, which included individual prenatal counselling and a community-wide promotion and education campaign, was developed to improve the rates. The study group consisted of all Chinese women delivering in 1980 and 1981 who had taken their infants to one pediatrician for continuing care. The rates of breast-feeding in the 88 women who had received prenatal counselling and the 93 women who had not were compared. Although the rates were substantially increased for both groups over the 1977-79 rate (54% and 34% in 1980 and 65% and 55% in 1981 respectively), the 2-year rate was significantly higher for the counselled group compared with the uncounselled group in the later study (59% v. 43%). The greatest effect of counselling was seen in young, primiparous women of higher socioeconomic status who spoke French or English in addition to Chinese. However, 33% of the counselled women who had started breast-feeding had stopped by 1 month, compared with only 15% of the uncounselled women. Thus, although the rates of breast-feeding in ethnic groups can be increased with the use of a language- and culture-specific approach, more support and encouragement must be given to women who start breast-feeding so that they will continue longer.


Representations of regular and irregular shapes by deep Convolutional Neural Networks, monkey inferotemporal neurons and human judgments.
Recent studies suggest that deep Convolutional Neural Network (CNN) models show higher representational similarity, compared to any other existing object recognition models, with macaque inferior temporal (IT) cortical responses, human ventral stream fMRI activations and human object recognition. These studies employed natural images of objects. A long research tradition employed abstract shapes to probe the selectivity of IT neurons. If CNN models provide a realistic model of IT responses, then they should capture the IT selectivity for such shapes. Here, we compare the activations of CNN units to a stimulus set of 2D regular and irregular shapes with the response selectivity of macaque IT neurons and with human similarity judgements. The shape set consisted of regular shapes that differed in nonaccidental properties, and irregular, asymmetrical shapes with curved or straight boundaries. We found that deep CNNs (Alexnet, VGG-16 and VGG-19) that were trained to classify natural images show response modulations to these shapes that were similar to those of IT neurons. Untrained CNNs with the same architecture than trained CNNs, but with random weights, demonstrated a poorer similarity than CNNs trained in classification. The difference between the trained and untrained CNNs emerged at the deep convolutional layers, where the similarity between the shape-related response modulations of IT neurons and the trained CNNs was high. Unlike IT neurons, human similarity judgements of the same shapes correlated best with the last layers of the trained CNNs. In particular, these deepest layers showed an enhanced sensitivity for straight versus curved irregular shapes, similar to that shown in human shape judgments. In conclusion, the representations of abstract shape similarity are highly comparable between macaque IT neurons and deep convolutional layers of CNNs that were trained to classify natural images, while human shape similarity judgments correlate better with the deepest layers.


Human Milk Glucose, Leptin, and Insulin Predict Cessation of Full Breastfeeding and Initiation of Formula Use.
Objective: We aimed to investigate prospective associations between milk bioactives related to metabolic health (glucose, insulin, leptin, C reactive protein [CRP], and interleukin 6 [IL-6]) and incident formula initiation at 3 and 6 months postpartum. Design: This study included 363 mother-infant dyads who were fully breastfed at 1 month and participated in the prospective Mothers and Infants Linked for Healthy Growth study from pregnancy to 6 months postpartum. Associations between milk glucose, leptin, insulin, CRP, and IL-6 at 1 and 3 months and incident formula feeding (FF) at 3 and 6 months, respectively, were tested using multiple logistic regression, adjusting for numerous potential confounders such as maternal age and prepregnancy body mass index. Results: At 3 months postpartum, 1-month glucose (odds ratio [OR] 0.45 [95% confidence interval (CI): 0.27-0.75], p ≤ 0.01) and smaller decreases in glucose from 1 to 3 months (OR 0.51 [95% CI: 0.28-0.92], p = 0.03) were associated with lower odds of FF, whereas 1-month leptin (OR 2.30 [95% CI: 1.30-4.07], p < 0.01) and larger increase in insulin (OR 1.86 [95% CI: 1.23-2.81], p < 0.01) and leptin (OR 2.17 [95% CI: 1.29-3.68], p < 0.01) from 1 to 3 months were associated with increased odds of FF. At 6 months, insulin increases (OR 2.08 [95% CI: 1.03-4.17], p = 0.04) were associated with higher odds of FF. Conclusions: In a cohort of women with established lactation, 1-month milk glucose, insulin, and leptin predicted initiation of FF at 3 months. Early milk composition may provide a window into mammary gland function, allowing identification of women at risk of not meeting their breastfeeding goals.


Chemical Dispersant Enhances Microbial Exopolymer (EPS) Production and Formation of Marine Oil/Dispersant Snow in Surface Waters of the Subarctic Northeast Atlantic.
A notable feature of the Deepwater Horizon oil spill was the unprecedented formation of marine oil snow (MOS) that was observed in large quantities floating on the sea surface and that subsequently sedimented to the seafloor. Whilst the physical and chemical processes involved in MOS formation remain unclear, some studies have shown that extracellular polymeric substances (EPS) play a role in this process. Here, we report that during exposure of subarctic northeast Atlantic seawater to a chemical dispersant, whether in the presence/absence of crude oil, the dispersant stimulates the production of significant quantities of EPS that we posit serves as a key building block in the formation of MOS. This response is likely conferred via de novo synthesis of EPS by natural communities of bacteria. We also describe the formation of marine dispersant snow (MDS) as a product of adding chemical dispersants to seawater. Differential staining confirmed that MDS, like MOS, is composed of glycoprotein, though MDS is more protein rich. Using barcoded-amplicon Illumina MiSeq sequencing, we analyzed, for the first time, the bacterial communities associated with MDS and report that their diversity is not significantly dissimilar to those associated with MOS aggregates. Our findings emphasize the need to conduct further work on the effects of dispersants when applied to oil spills at sea, particularly at different sites, and to determine how the product of this (i.e., MOS and MDS) affects the biodegradation of the oil.


Distinct guard cell specific remodeling of chromatin accessibility during abscisic acid and CO2 dependent stomatal regulation.
In plants, epidermal guard cells integrate and respond to numerous environmental signals to control stomatal pore apertures thereby regulating gas exchange. Chromatin structure controls transcription factor access to the genome, but whether large-scale chromatin remodeling occurs in guard cells during stomatal movements, and in response to the hormone abscisic acid (ABA) in general, remain unknown. Here we isolate guard cell nuclei from Arabidopsis thaliana plants to examine whether the physiological signals, ABA and CO2, regulate guard cell chromatin during stomatal movements. Our cell type specific analyses uncover patterns of chromatin accessibility specific to guard cells and define novel cis-regulatory sequences supporting guard cell specific gene expression. We find that ABA triggers extensive and dynamic chromatin remodeling in guard cells, roots, and mesophyll cells with clear patterns of cell-type specificity. DNA motif analyses uncover binding sites for distinct transcription factors enriched in ABA-induced and ABA-repressed chromatin. We identify the ABF/AREB bZIP-type transcription factors that are required for ABA-triggered chromatin opening in guard cells and implicate the inhibition of a set of bHLH-type transcription factors in controlling ABA-repressed chromatin. Moreover, we demonstrate that ABA and CO2 induce distinct programs of chromatin remodeling. We provide insight into the control of guard cell chromatin dynamics and propose that ABA-induced chromatin remodeling primes the genome for abiotic stress resistance.


[Role of peroxidation in destruction of membrane lipids under conditions of liver ischemia].
Alterations in phospholipid and fatty acid composition were studied in homogenates, mitochondrial, microsomal and nuclear fractions during intensification of lipid peroxidation under conditions of liver tissue ischemia. Increase in content of lipid hydroperoxides and decrease in content of arachidonic acid were observed in lipids of all the membranes studied. Content of individual phospholipids altered depending on their susceptibility to peroxidation. In ischemia content of total lipids and phospholipids was decreased. The data obtained suggest the important role of peroxidation in impairment of membrane lipids under conditions of ischemia.


Assessment of volume measurement of the prostate using per-rectal ultrasonography.
A study was made of 100 cadaveric prostates (71 benign glands and 29 invaded by adenocarcinoma) using a technique that enabled per-rectal ultrasonography to be carried out and their volumes measured by computed planimetry. These volumes were compared directly with the actual volumes of the glands measured after dissection from the cadaver specimens. A high degree of correlation was obtained for the measurement of benign glands (r = 0.982) and glands containing cancers confined within the capsule (r = 0.961). Estimation of the size of cancers unconfined to the gland was poor and measurement was not possible with 3 malignant prostates that had extended beyond the prostatic capsule so that the ultrasonic boundary could not be defined.


Combination of curcumin and piperine prevents formation of gallstones in C57BL6 mice fed on lithogenic diet: whether NPC1L1/SREBP2 participates in this process?
A disruption of cholesterol homeostasis characterized by the physical-chemical imbalance of cholesterol solubility in bile often results in formation of cholesterol gallstones. Our earlier studies revealed that curcumin (1000 mg/kg) could prevent formation of gallstones. It has been proved that curcumin is poorly absorbed while piperine is a bioavailability-enhancer. Nevertheless, whether curcumin combined with piperine could enhance the effect of curcumin in preventing gallstones is still awaited. C57BL6 mice were fed on a lithogenic diet concomitant with curcumin at 500 or 1000 mg/kg and/or piperine at 20 mg/kg for 4 weeks. The ratio of gallbladder stone formation was recorded and samples of blood, bile, gallbladder, liver and small intestine were also collected. The volume of gallbladder and weight of liver were calculated, and blood and bile samples were analyzed through biochemical methods. Intestinal NPC1L1 and SREBP2 mRNA and protein expression were detected by real-time PCR and Western blot. Combining with piperine can significantly enhance the effect of curcumin, thus preventing the development of gallbladder stones, lowering the saturation of blood lipids and cholesterol in bile, as well as decreasing the expression of NPC1L1 and SREBP2 in both mRNA and protein levels. Curcumin can prevent the formation of cholesterol gallstones induced by high fat diet in mice and SREBP2 and NPC1L1 may participate in this process. Piperine can increase curcumin's bioavailability, thereby enhancing the effect of curcumin.


X-linked Hunter syndrome: the heterozygous phenotype in cell culture.
Fibroblast cultures derived from the skin of three Hunter heterozygotes have been examined for iduronate sulfatase deficiency primarily by measurement of [35S]-mucopolysaccharide accumulation in the presence and absence of Hunter corrective factor. For each heterozygote, two populations of clones were observed: normal and enzyme deficient, as predicted by the Lyon hypothesis. However, the phenotype of the uncloned cultures was usually normal, presumably because of cross-correction, even after storage in liquid N2. Mixing experiments indicate that the presence of a majority of cells with the Hunter phenotype may be obscured as the result of correction by the minority population of normal cells in the mixture. Variability in the ability to cross-correct was also demonstrated. The unpredictable behavior of uncloned cultures make them unsuitable for diagnosing the Hunter carrier state.


Mussel-Inspired Self-Healing Coatings Based on Polydopamine-Coated Nanocontainers for Corrosion Protection.
The mussel-inspired properties of dopamine have attracted immense scientific interest for surface modification of nanoparticles due to the high potential of dopamine functional groups to increase the adhesion of nanoparticles to flat surfaces. Here, we report for the first time a novel type of inhibitor-loaded nanocontainer using polydopamine (PDA) as a pH-sensitive gatekeeper for mesoporous silica nanoparticles (MSNs). The encapsulated inhibitor (benzotriazole) was loaded into MSNs at neutral pH, demonstrating fast release in an acidic environment. The self-healing effect of water-borne alkyd coatings doped with nanocontainers was achieved by both on-demand release of benzotriazole during the corrosion process and formation of the complexes between the dopamine functional groups and iron oxides, thus providing dual self-healing protection for the mild steel substrate. The coatings were characterized by electrochemical impedance spectroscopy, visual observations, and confocal Raman microscopy. In all cases, the coatings with embedded benzotriazole-loaded MSNs with PDA-decorated outer surfaces demonstrated superior self-healing effects on the damaged areas. We anticipate that dopamine-based multifunctional gatekeepers can find application potential not only in intelligent self-healing anticorrosive coatings but also in drug delivery, antimicrobial protection, and other fields.


Recidivism in congenital cholesteatoma surgery.
Forty-four cases of congenital cholesteatoma in the pediatric age group have been treated surgically. There have been three residual cholesteatomas, which were localized to the anterior aspect of the malleus and were easily excised. Two cases of postero-superior retraction pockets developed post-operatively, and these were treated by conventional tympanomastoid surgery with excision of the retraction pocket and grafting. All five of the patients with recidivism have experienced no further difficulty.