Red blood cell distribution width as a potential predictor of survival of pulmonary arterial hypertension associated with primary Sjogren's syndrome: a retrospective cohort study.
Pulmonary arterial hypertension (PAH) is a severe complication and leading cause of mortality in patients with primary Sjogren's syndrome (pSS). This study was to investigate the overall survival rates and the utility of red blood cell distribution width (RDW) as a potential prognostic factor of pSS-PAH. This cohort study retrospectively enrolled 55 patients with pSS-PAH who were followed up at the Department of Rheumatology of Peking Union Medical College Hospital (PUMCH) between August 2007 and May 2017. The patients were stratified according to the level of RDW (≤ 15.0 and > 15.0%). Baseline demographics, laboratory results, pulmonary function conditions, hemodynamic assessments, and treatment regimens were analyzed. Cox proportional hazards regression analysis was used to identify whether RDW level is a factor related to adverse outcome. A total of 55 patients were recruited, with an average age of 38.9 ± 9.3 years. Fifty-four were female (98.2%), and the average duration at the time of PAH diagnosis was 25.5 ± 33.2 months. Higher RDW levels were found in patients who deceased in follow-up (13.8 ± 2.6 vs 16.5 ± 1.6%, p = 0.003) and with higher NYHA classes (13.8 ± 1.8 vs 16.5 ± 2.9%, p < 0.001). Patients with RDW > 15% had a significantly worse overall survival than patients with RDW ≤ 15% (3-year survival rate 59.5 vs. 88.7% log-rank p = 0.015). Cox regression analysis identified RDW > 15% as a prognostic factor for adverse outcome (HR 1.786, 95% CI 1.137-2.803, p = 0.012). RDW can serve as a potential negative prognostic factor of pSS-PAH.


Visible-light-activated photoelectrochemical biosensor for the study of acetylcholinesterase inhibition induced by endogenous neurotoxins.
In this report, a novel visible-light-activated photoelectrochemical biosensor was fabricated to study the inhibition of acetylcholinesterase (AChE) activity induced by two endogenous neurotoxins, 1(R)-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [(R)-Sal] and 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetra-hydroisoquinoline [(R)-NMSal], which have drawn much attention in the study of the pathogenesis of neurodegenerative diseases such as Parkinson's disease. The photoelectrode was prepared by three steps, as follows. At first, nitrogen and fluorine co-doped TiO2 nanotubes (TNs) were obtained by anodic oxidation of a Ti sheet. Secondly, silver nanoparticles (AgNPs) were deposited onto the TNs through a microwave-assisted heating polyol (MAHP) process. At last, AChE was immobilized on the obtained photoelectrode and the biosensor was marked as AChE/Ag/NFTNs. Due to the nitrogen and fluorine co-doping, the photoelectrochemical biosensors can produce high photocurrent under visible light irradiation. Moreover, the presence of AgNPs greatly increased the photocurrent response of the biosensor. AChE/Ag/NFTNs hybrid system was used to study AChE inhibition induced by (R)-Sal and (R)-NMSal. The result proved that both (R)-Sal and (R)-NMSal exhibited mixed and reversible inhibition against AChE. This strategy is of great significance for the development of novel photoelectrochemical biosensors in the future.


Cardiovascular events in type 2 diabetes: comparison with nondiabetic individuals without and with prior cardiovascular disease. 10-year follow-up of the Hoorn Study.
We questioned whether prior cardiovascular disease has the same impact on risk of cardiovascular events as type 2 diabetes, and whether this differed between men and women. To address these issues we compared the 10-year risk of cardiovascular events among 208 Caucasian individuals with diabetes to that of 2253 Caucasian individuals without diabetes, in a population-based cohort study. Gender significantly modified the association between type 2 diabetes and cardiovascular events (p=0.01). The hazard ratio of cardiovascular events associated with the presence of diabetes was higher in women (adjusted hazard ratio, 1.8; 95% CI, 1.2 to 2.7) than in men (adjusted hazard ratio, 1.3; 0.9 to 2). As compared to men without diabetes but with prior cardiovascular disease, risk of cardiovascular events was significantly lower in men with diabetes but without prior cardiovascular disease (adjusted hazard ratio, 0.5; 0.3 to 0.9). In contrast, this risk was equal in women with diabetes but without prior cardiovascular disease and women without diabetes but with prior cardiovascular disease (adjusted hazard ratio, 1.0; 0.6 to 1.7; P for interaction between gender and diabetes=0.05). Women with diabetes but without prior cardiovascular disease have a risk of cardiovascular events that is similar to that of women without diabetes but with prior cardiovascular disease, whereas in men the presence of prior cardiovascular disease conferred a higher risk. These data emphasise the necessity of aggressive treatment of cardiovascular risk factors in women with type 2 diabetes.


Active Acoustic Monitoring of Aquatic Life.
Active acoustic monitoring (AAM) can be used to study the behavioral response of marine life and to mitigate harm during high-danger anthropogenic activities. This has been done in fish studies for many decades, and there are now case studies in which AAM has been used for marine mammal monitoring as well. This includes monitoring where the ranges, AAM frequency of operation, and species are such that the AAM operation is completely outside the hearing range of the animals. However, it also includes AAM operations within the hearing range of marine life, although this does not necessarily that imply AAM is not a suitable tool. It is just not always possible to have a sufficient detection and tracking range and operate at a frequency outside the marine life hearing range. Likely, the best and most important application of AAM is when the anthropogenic activity to be conducted is temporary and presents a clear danger to aquatic life.


Poly(A)+ RNA metabolism during change of physiological state of Tetrahymena pyriformis cells.
In the present work the metabolism of poly(A)+ RNA was investigated in cells of Tetrahymena pyriformis derived either from stationary cultures or from starved suspensions that were initiating growth. Under these circumstances the organisms derived from stationary cultures synthesize ribosomal and poly(A)+ RNA and form polysomes. In the presence of actinomycin D (actD) the observed expansion of the polysomal population is arrested. Pre-starved cells, on the other hand, start making polysomes in the virtual absence of ribosomal and poly(A)+ RNA synthesis soon after being transferred to peptone medium. In this case polysome formation is only partially sensitive to actD. These results have been interpreted as indicating that, in the beginning of growth, cells derived from stationary cultures are dependent on RNA synthesis for polysome formation, whereas pre-starved cells use pre-synthesized RNA for the same purpose.


A retrospective study of Patch test results from 163 patients with stasis dermatitis or leg ulcers. I. Discussion of the Patch test results and the sensitization indices and determination of the relevancy of positive reactions.
Patch test results from 163 patients with leg ulcers and/or chronic venous insufficiency, tested with a modified ICDRG standard test battery and a pharmaceutical test series, are analyzed and compared with the results obtained from a randomly selected control group of patients with eczematous conditions. A sensitization index for the most common contact allergens present in this test series is calculated, and the relevancy of hypersensitivity to specific topical agents is determined.


Association of human sperm nuclear decondensation and in vitro penetration ability.
Sperm nuclear decondensation is an integral step in fertilization which leads to the formation of the male pronucleus. The association between the in vitro spontaneous nuclear decondensation of human sperm and its fertilizing ability was studied in infertile male patients. The ability of sperm to fertilize an egg using the discontinuous two-layer Percoll method was significantly correlated to the percentage of decondensed swollen head (r = 0.43; P less than 0.005). The fertilizing ability of sperm processed with Test-Yolk buffer was correlated with the percentage of sperm at the fully decondensed stalk stage (r = 0.51; P less than 0.05). There were insignificant correlations for the whole-wash centrifugation, cryopreserved-thawed and swim-up methods. Samples of sperm that were positive (greater than 0% fertilization) in the sperm penetration assay had a higher percentage of decondensed sperm heads (66.7% vs. 20.6%) after Percoll wash or whole-wash centrifugation (60.5% vs. 44.3%) treatments compared with samples with no fertilization. Treatments that included Test-Yolk resulted in high percentages of decondensed swollen heads. The results suggest a positive association between sperm nuclear decondensation and the fertilizing ability of sperm, and affirm the importance of nuclear decondensation to the study of fertilization events.


Comparison of Long Term Follow-up Chest CT Imaging in Adult and Pediatric Patients with Humidifier Disinfectant-related Lung Injury.
To compare the chest computed tomography (CT) images of children and adults in families with clusters of humidifier disinfectant-related lung injury (HDLI) after cessation of exposure to humidifier disinfectant (HD). We reviewed medical records of 19 families with 43 patients (21 adults, 22 children) among families, which had at least one adult and one child with HDLI. Each family was exposed to the same HD exposure environment. In adults, centrilobular nodules were predominant (95.2%) in chronic HDLI findings after cessation of exposure to HD, however, in children, normal pattern was most prevalent on chest CT (45.5%), followed by centrilobular nodule (36.4%), bizarre lung cysts (36.4%), and reticulation (13.6%). Unlike the known chronic HDLI finding of adults, centrilobular nodules were only present in 36.4% of children. The frequency of bizarre lung cysts were significantly greater in children than that in adults after cessation of similar exposure to HD. Thus, bizarre lung cysts may be useful as another novel finding of chronic HDLI in children who have no history of pulmonary infection or other perinatal disorder such as hyaline membrane disease or other interstitial lung disease.


[Interstitial granulomatous dermatitis with arthritis: four cases].
Interstitial granulomatous dermatitis with arthritis, or Ackerman's syndrome, is characterized by inflammatory articular flares of potentially destructive outcome and cutaneous lesions of varied patterns: cord-like lesions on the flanks or violaceous plaques on the trunk and limbs. Histologically, the main features are histiocytes laminated between collagen fibres, sometimes organized in rosettes comprising tiny granulomas surrounding fibres of homogeneous aspect. Four patients fitting this description were investigated. Cutaneous lesions displayed various patterns: cord-like lesions (one patient), brown plaques on the flanks edged with papules (one patient), grossly annular violaceous plaques on the back (one patient), and infiltrated plaques on the palms and thighs (one patient). Joint symptoms were present in all cases (one seropositive rheumatoid arthritis and one seronegative rheumatoid arthritis, both already known; acute rheumatoid arthritis in two cases). The histological pattern was quite similar in all cases, with laminated histiocytes in palisading layers mixed with swollen collagen fibres; "rosette" figures were present in two cases. Autoimmune response was seen with antinuclear antibodies (two cases) and/or rheumatoid factor (two cases). The short-term outcome of cutaneous lesions was rapidly favourable in most cases with systemic steroids (one case) or Non Steroidal Anti-Inflammatory Drugs (one case), and spontaneously in one case. This entity, defined by the presence of inflammatory arthritis and cutaneous lesions of various clinical types, either more specific but infrequent (cord-like), or less specific but more frequent (plaque-like), and featuring a peculiar histological pattern, chiefly affects women aged between 30 and 80 years. Pathophysiological mechanisms and nosological borders are debatable and authors consider this condition as either an autonomous disease or else a mere subset of vasculitis with palisading granulomas in collagen vascular disorders, despite the rarity of authentic vasculitis. A setting of autoimmunity is frequently present. Furthermore, a fairly similar histological pattern is sometimes seen in some lesions forming a subset of cutaneous side-effects of drugs. Articular outcome may be unfavourable with joint destruction in more than half of patients, whether or not in a setting of rheumatoid arthritis. Spontaneous resorption can occur. Treatment has not yet been codified and is based primarily on anti-inflammatory drugs.


Perioperative outcomes of patients with restless legs syndrome: a single-center retrospective review.
There are multiple stressors in the perioperative period for patients with restless legs syndrome (RLS) that may be implicated in the worsening of symptoms. Our primary objective was to compare the perioperative course of patients with RLS to patients without the diagnosis. This was a single-center, matched-cohort, retrospective chart review of patients with RLS undergoing inpatient procedures from 2015-2019 matched 1:1 with patients without the diagnosis. Patients with RLS had a higher comorbidity burden; specifically, pulmonary, renal, diabetes mellitus, and congestive heart failure. The perioperative course was notable for higher maximum pain scores for patients with RLS in the postanesthesia care unit (odds ratio, 1.29; 95% confidence interval, 1.19-1.40; P < .001). Postoperative patients with RLS also had higher maximum pain scores on postoperative days 0, 1, and 2. The odds of rapid-response calls were higher in patients with RLS (odds ratio, 1.43; 95% confidence interval, 1.18-1.73; P < .001). There were no other significant differences in postoperative complications. The odds of using RLS-triggering medications were lower in the RLS group (odds ratio, 0.85; 95% confidence interval, 0.78-0.92; P < .001). Our single-center retrospective review found that patients with RLS had higher pain scores in the postanesthesia care unit and on the first few postoperative days. Rapid-response team calls were more common in patients with RLS. RLS-triggering medications were significantly less likely to be used in patients with RLS. There were no significant differences in other postoperative events. Gali B, Silber MH, Hanson AC, Portner E, Gay P. Perioperative outcomes of patients with restless legs syndrome: a single-center retrospective review. J Clin Sleep Med. 2022:18(7):1841-1846.


Individuals with sessile serrated polyps express an aggressive colorectal phenotype.
Sessile serrated polyps are precursors of colorectal cancer arising from molecular pathways distinct from conventional adenomas. The association between sessile serrated polyps and conventional adenomas is not well known. We hypothesize that individuals who have coexistent sessile serrated polyps and conventional adenomas express a more severe phenotype than those harboring lesions from only one pathway. We compare colorectal phenotypes among individuals with sessile serrated polyps, those with conventional adenomas, and those expressing both. This investigation is a retrospective cross-sectional study of 3 cohorts. This study was conducted in multiple centers within 1 health care system. Individuals with sessile serrated polyps and/or conventional adenomas on first lifetime colonoscopy were included in the study. The demographics and polyp characteristics were compared among 3 cohorts to determine the differences in phenotypic expression. Two hundred sixty individuals with sessile serrated polyps and 173 with only conventional adenomas were included. The disease phenotype was most severe in individuals with coexistent sessile serrated polyps and adenomas. The sessile serrated polyps in this cohort were larger (P = .01) than in the serrated-only cohort. The conventional adenomas in this cohort were more numerous (P = .035) and more advanced (P = .046) than in the adenoma-only cohort. Synchronous colorectal cancers were found exclusively in the cohorts with sessile serrated polyps, although this did not reach statistical significance (P = .06). Cross-sectional design precluded the ability to assess for metachronous lesions. Sessile serrated polyps, but not all polyps, were reviewed. Individuals who coexpress sessile serrated polyps and conventional adenomas have an aggressive colorectal phenotype. They harbor larger sessile serrated polyps and more numerous and advanced adenomas than individuals with only sessile serrated polyps or adenomas. Synchronous colorectal cancers were found exclusively in cohorts with sessile serrated polyps. Individuals with sessile serrated polyps, especially with coexistent conventional adenomas, appear to be a high-risk group, which needs to be accounted for when calculating postpolypectomy surveillance intervals.


An investigation of three types of multiple choice questions.
The present paper reports of the results of a preliminary evaluation of the A, and K, and E type multiple choice question.


Protonation of the sarcoplasmic reticulum Ca-ATPase during ATP hydrolysis.
pH changes of the reaction medium (pH 6.35) following addition of MgATP were determined at 4 degrees C with sarcoplasmic reticulum vesicles in the presence of 0.1 mM CaCl2 and 5 mM MgCl2. With intact vesicles, a pronounced acidification following a slight alkalinization was induced by MgATP, indicating H+ ejection from vesicles. This agrees with previous observations by several investigators that suggested H+ counter-transport coupled to Ca2+ uptake. When vesicles were made leaky, a markedly enhanced alkalinization occurred after addition of MgATP, and then the pH returned to the level before the MgATP addition. The decay of this alkalinization coincided with the disappearance of phosphoenzyme (EP) which was formed from MgATP and the Ca-ATPase of sarcoplasmic reticulum. The CaCl2 concentration dependence of the alkalinization agreed well with that of EP formation. Furthermore, the alkalinization was prevented by modification of a specific SH group of the enzyme essential for EP decomposition. These findings give evidence that the alkalinization with leaky vesicles represents protonation of the enzyme during ATP hydrolysis. The enhanced alkalinization with leaky vesicles suggests protonation occurring inside vesicles. When CaATP in place of MgATP was added in the absence of MgCl2, neither the H+ ejection from intact vesicles nor the enhanced alkalinization with leaky vesicles occurred. Under these conditions, CaATP did not efficiently support active Ca2+ uptake. These results are compatible with the view that the observed protonation could represent an initial event occurring inside vesicles in the H+ countertransport coupled to Ca2+ uptake.


Posterior circulation infarction: anatomy, pathophysiology, and clinical correlation.
Posterior circulation cerebrovascular disease may be responsible for clinical syndromes that are determined by the vascular territory affected. An anatomic/topographic approach to the brain stem and cerebellum, relating the cross-sectional and functional anatomy to the vascular supply territories, is useful in the analysis of imaging studies of patients with posterior circulation cerebrovascular disease. Knowledge of the typical vascular distributions may be particularly useful for cases that do not show the classical clinical brain stem and cerebellar infarction syndromes. This approach may serve to improve our understanding of cerebrovascular disease in the posterior fossa.


Mapping Quantitative Trait Loci (QTL) in sheep. III. QTL for carcass composition traits derived from CT scans and aligned with a meta-assembly for sheep and cattle carcass QTL.
An (Awassi × Merino) × Merino single-sire backcross family with 165 male offspring was used to map quantitative trait loci (QTL) for body composition traits on a framework map of 189 microsatellite loci across all autosomes. Two cohorts were created from the experimental progeny to represent alternative maturity classes for body composition assessment. Animals were raised under paddock conditions prior to entering the feedlot for a 90-day fattening phase. Body composition traits were derived in vivo at the end of the experiment prior to slaughter at 2 (cohort 1) and 3.5 (cohort 2) years of age, using computed tomography. Image analysis was used to gain accurate predictions for 13 traits describing major fat depots, lean muscle, bone, body proportions and body weight which were used for single- and two-QTL mapping analysis. Using a maximum-likelihood approach, three highly significant (LOD ≥ 3), 15 significant (LOD ≥ 2), and 11 suggestive QTL (1.7 ≤ LOD < 2) were detected on eleven chromosomes. Regression analysis confirmed 28 of these QTL and an additional 17 suggestive (P < 0.1) and two significant (P < 0.05) QTL were identified using this method. QTL with pleiotropic effects for two or more tissues were identified on chromosomes 1, 6, 10, 14, 16 and 23. No tissue-specific QTL were identified.A meta-assembly of ovine QTL for carcass traits from this study and public domain sources was performed and compared with a corresponding bovine meta-assembly. The assembly demonstrated QTL with effects on carcass composition in homologous regions on OAR1, 2, 6 and 21.


Fetal zinc deficiency as a mechanism for cadmium induced toxicity to the developing rat lung and pulmonary surfactant.
Maternal exposure to cadmium alters lung and pulmonary surfactant development in the rat fetus. A toxic property of cadmium is its biological interaction with the essential trace metal zinc. The present study was undertaken to determine the role of zinc in the induction of fetal anomalies by cadmium. Pregnant rats were injected with 8 mg/kg cadmium chloride alone or with 12 mg/kg zinc chloride on gestation days 12-15 and sacrificed on gestation day 21. Controls received injections of saline and zinc chloride. Pulmonary surfactant phospholipids were isolated from fetal lungs and quantified. Concentrations of cadmium and zinc in maternal and fetal tissues and placenta were measured. Cadmium treatment caused embryonic death, lung hypoplasia and diminished quantity of the major pulmonary surfactant phospholipid, phosphatidylcholine. Zinc treatment alone did not alter normal fetal development. Coadministration of zinc with cadmium prevented all of the previously observed cadmium-induced fetotoxicity. The placenta appeared to act as a barrier to cadmium movement, as cadmium was found in the placenta but not in fetal tissues. However, cadmium treatment decreased fetal zinc content. Simultaneous injection of zinc with cadmium maintained the fetal zinc concentration at the control level. Thus cadmium appears to exert its fetotoxic effects indirectly, through a fetal zinc deficiency.


Perturbation of lipid membranes by organic pollutants.
The ability of a range of organic pollutants--hexachlorobenzene, mirex(1,1a,2,2,3,3a,4,5,5,5a,5b,6-dodecachlorooctahydro-1,3,4-metheno-1H cyclobuta(cd) pentalene), 1,3,5-trichlorobenzene, 2,4,6-trichlorophenol, p-nitrophenol, p-chlorophenol, DDT, and pentachlorophenol--to perturb liposomes of dipalmitoyl phosphatidylcholine (DPPC) has been measured by differential scanning calorimetry. The degree of perturbation was measured by the increase in breadth of the main DPPC phase transition in both heating and cooling scans. DDT and the phenol derivatives were effective perturbers of phospholipid, broadening the transition by as much as 12-fold. Hexachlorobenzene and mirex did not perturb at all when mixed with DPPC at concentrations as high as 20 mol%, although 1,3,5-trichlorobenzene caused slight broadening of the main transition at this concentration. Perturbation is facilitated by the presence of a hydroxyl group on the benzene ring and hindered by increasing degrees of chloride substitution. An apparent correlation exists between the extent of phospholipid perturbation measured by differential scanning calorimetry and LD50 values for these compounds taken from the literature. This suggests the possibility of formulating an "index of perturbation" which could be used to screen certain classes of organic compounds for potential biological toxicity on a routine basis.


Intravascular macrophages in cardiac allograft biopsies for diagnosis of early and late antibody-mediated rejection.
The aim of our study was to evaluate the role of intravascular macrophages in the diagnosis of early and late antibody-mediated rejection (AMR) on endomyocardial biopsies (EMBs). We reviewed 1,420 consecutive EMBs from 131 patients and selected 75 C4d+ EMBs. The C4d+ group was compared with a control group (66 patients) matched for age, gender, date of transplantation, follow-up, immunosuppressive regimen and primary heart disease. A total of 141 EMBs were evaluated. Immunoperoxidase staining for C4d and CD68 were performed. Post-transplant IgG anti-HLA reactivity was investigated by Luminex technology. Clinical data were also collected. Fourteen EMBs were available from 11 symptomatic AMR patients. Of the 141 EMBs evaluated, 53 were positive for intravascular macrophages (CD68); among them, 32 were also positive for C4d (32 of 53, 60.4%). Of the 88 CD68- EMBs, 43 were also C4d+ (43 of 88, 48.9%). Of the 53 CD68+ EMBs, 30 EMBs were within the first year since transplantation (30 of 53, 57.8%), and among these 21 were also positive for C4d (21 of 30, 70.0%). In the late period, among the 23 CD68+ EMBs (23 of 53, 42.2%) 11 were also positive for C4d (11 of 23, 47.8%). In the early period, intravascular macrophages were more common in symptomatic (3 of 3, 100%) than asymptomatic (3 of 11, 27.3%) patients. Sensitivity and specificity of intravascular macrophages in predicting donor-specific antibodies (DSA) within the first year were 50.0% and 100.0%, respectively. Intravascular macrophages predict C4d, DSA and symptoms early after transplantation; however, in the late period, they are unable to identify patients with circulating DSA, C4d and/or symptoms.


Novel conditional plasmids regulated by chemical switches provide versatile tools for genetic engineering in Escherichia coli.
Engineering bacterial genomes or foreign DNA cloned as bacterial artificial chromosomes (BACs) relies on usage of helper plasmids, which deliver the desired tools transiently into the bacteria to be modified. After the anticipated action is completed the helper plasmids need to be cured. To make this efficient, plasmids are used that are maintained by conditional amplicons or carry a counter-selection marker. Here, we describe new conditional plasmids that can be maintained or cured by using chemical induction or repression. Our method is based on the dependency of plasmids carrying ori6Kγ origin of replication on the presence of protein Π. Ori6Kγ based plasmids are tightly regulated conditional constructs, but they require usually special E. coli strains to operate. To avoid this, we placed the Π protein expression under the control of a co-expressed conditional repressor. Regulating the maintenance of plasmids with administration or removal of chemicals is fully compatible with any other conditional amplicons applied to date. Here, we describe methods for inducing sites specific recombination of BACs as an example. However, the same strategy might be used to construct appropriate helper plasmids for any other transient components of genome editing methodologies such as λred recombinases or CRISPR/Cas components.


Postmenopausal Invasive Endometriosis Requiring Supralevator Pelvic Exenteration.
Endometriosis is rare in postmenopausal women. We report a case of invasive pelvic endometriosis in a postmenopausal woman requiring a supralevator pelvic exenteration for palliation of symptoms and for tissue diagnosis. A 65-year-old woman with a history of total abdominal hysterectomy and bilateral salpingo-oophorectomy for endometriosis at age 43 years presented with acute vaginal bleeding, hematuria, and a recently diagnosed pelvic mass. Biopsies revealed endometriosis, and she underwent supralevator pelvic exenteration with vaginectomy, end colostomy, ileal conduit, and coagulation of endometriotic implants. Pathologic examination showed invasive endometriosis and no evidence of malignancy. Endometriosis should remain on the differential diagnosis for pelvic mass in a postmenopausal woman, although suspicion for malignancy should remain high.


Formulation optimization, in vitro and in vivo evaluation of agomelatine-loaded nanostructured lipid carriers for augmented antidepressant effects.
The present study was intended to prepare and optimize agomelatine-loaded nanostructured lipid carriers (AGM-NLCs) for augmented in vivo antidepressant potential. AGM-NLCs were optimized on several parameters including cumulative hydrophilic-lipophilic balance of surfactants, proportions of solid and liquid lipids, total amounts of drug and surfactants. AGM-NLCs were assessed for their physicochemical properties, in vitro AGM release and in vivo antidepressant effects in mice model. The optimized AGM-NLCs demonstrated spherical morphology with average particle size of 99.8 ± 2.6 nm, PDI of 0.142 ± 0.017, zeta potential of - 23.2 ± 1.2 mV and entrapment efficiency of 97.1 ± 2.1%. Thermal and crystallinity studies depict amorphous nature of AGM after its incorporation into NLCs. AGM-NLCs exhibit a sustained drug release profile after initial 2 h. Mice treated with AGM-NLCs exhibited reduced immobility time in behavioral analysis. Furthermore, cresyl violet staining demonstrated an improved neuronal morphology and survival in AGM-NLCs group. The concentrations and the expression of inflammatory markers (TNF-α and COX-2) in mice brain were significantly reduced by AGM-NLCs. Taken together, therapeutic effectiveness of AGM was markedly augmented in AGM-NLCs and thereby they could be promising nanocarriers for the effective delivery of antidepressants to brain.


New and alternative modes of mechanical ventilation in neonates.
Innovative ventilation modes for infants attempt to reduce volume-induced lung damage, to decrease airway pressure and oxygen exposure, and to improve patient comfort. Volume-targeted ventilation results in more consistent tidal volumes, allows automatic weaning of airway pressure, may avoid hypocapnia and may be associated with long-term clinical benefits. Pressure support ventilation allows the patient to control the duration of mechanical breaths. It requires a stable respiratory drive or back-up for apnoea. Pressure support ventilation may be effective for weaning. Proportional assist ventilation was studied in small animal species. In preterm infants with acute and chronic lung disease, ventilator pressure requirements were lower in cross-over short-term comparisons with conventional triggered ventilation. Neurally adjusted ventilatory assist delivers ventilator pressure in proportion and in synchrony with the phasic inspiratory diaphragmatic electrical activity obtained from intra-oesophageal electrodes. Large multicentre clinical trials are required to prove long-term clinical benefits of these new modes.


Understanding Millennial Moms' Choices: A Nursing Survey About Childbirth Education in Primigravid Women.
Primigravid women, at some point, feel the need to gain education about childbirth. Our objective was to identify where primigravid millennial moms are seeking their childbirth education. This study, a quantitative nonexperimental survey research, was designed within the context of developmental transition theory. Childbearing women were recruited, considering the phenomenon to be studied. This purposive sample of 100 participants included primigravid millennial mothers (born between 1978 and 1994), status post vaginal birth, or emergent cesarean surgery, on a 455-bed, acute care facility. All participants were able to speak, understand, and read English or Spanish fluently. The author used a self-report survey to collect data from the participants. Primigravid women responded to a series of questions posed by the investigator. Considering the participants' variety of reading levels and their ability to communicate in writing, special attention was given to the simplicity and clarity of the questions on the survey. The responses provided by the participants suggested the need to enhance current childbirth education into culturally friendly and evidence-based technological information. Websites, apps, and social media are important information channels to reach and disseminate valuable childbirth education for millennial primigravid women. However, these channels are not currently being used to their full potential, considering the amount of information available and lack of guidance and clarity to disseminate trustworthy health-care information. By understanding millennial moms' choices, we gain the opportunity to deliver better education and support to Internet savvy women who are seeking online health-care information.


Open and laparoscopic adrenalectomy: analysis of the National Surgical Quality Improvement Program.
Numerous series demonstrate the benefits of laparoscopic versus open adrenalectomy, but fail to adjust for confounding factors. This study uses the Veterans Affairs National Surgical Quality Improvement Program database to compare these two approaches, adjusting for baseline differences. Laparoscopic (n=358) and open (n=311) adrenalectomy data were collected at 123 Department of Veterans Affairs and 14 university hospitals from October 1, 2001 to September 30, 2004. Preoperative characteristics, operative data, and 30-day outcomes were compared using the chi-square or Fisher's exact test for categorical variables and the t-test for continuous variables. Unadjusted odds ratio (OR) and 95% confidence interval (CI) were computed for the effect of operative approach on postoperative morbidity. Adjusted odds ratios and 95% CI were computed for this same effect, adjusting for variables that were predictive of outcomes or imbalanced at baseline. Data are reported as means +/-SD, unless otherwise indicated. Patients undergoing open adrenalectomy were more likely to be older (57.8+/-11.9 years versus 53.5+/-13.2 years, p < 0.0001), harbor malignancy (44.5% versus 13.5%, p < 0.0001), have higher American Society of Anesthesiologists classifications (p=0.0037), smoke (35.4% versus 22.6%, p=0.0003), and have lower serum albumin levels (3.9+/-0.5 g/dL versus 4.0+/-0.5 g/dL, p=0.0241). Open procedures had increased operative times (3.9+/-1.8 hours versus 2.9+/-1.3 hours, p < 0.0001), transfusion requirements (0.7+/-1.8 U versus 0.1+/-0.5 U, p<0.0001), reoperations (4.8% versus 1.4%, p=0.0094), length of stay (9.4+/-11.0 days versus 4.1+/-4.7 days, p < 0.0001) and 30-day morbidity rates (17.4% versus 3.6%, p < 0.0001) with unadjusted and adjusted odds ratio (95% CI) of 5.52 (2.94, 10.33), and 3.97 (1.92, 8.22), respectively. Open procedures resulted in more pneumonia, unplanned intubation, unsuccessful ventilator wean, systemic sepsis, cardiac arrest, renal insufficiency, and wound infections. Even after adjustment for confounding factors, 30-day morbidity was much higher for patients having open adrenalectomy.


ViromeScan: a new tool for metagenomic viral community profiling.
Bioinformatics tools available for metagenomic sequencing analysis are principally devoted to the identification of microorganisms populating an ecological niche, but they usually do not consider viruses. Only some software have been designed to profile the viral sequences, however they are not efficient in the characterization of viruses in the context of complex communities, like the intestinal microbiota, containing bacteria, archeabacteria, eukaryotic microorganisms and viruses. In any case, a comprehensive description of the host-microbiota interactions can not ignore the profile of eukaryotic viruses within the virome, as viruses are definitely critical for the regulation of the host immunophenotype. ViromeScan is an innovative metagenomic analysis tool that characterizes the taxonomy of the virome directly from raw data of next-generation sequencing. The tool uses hierarchical databases for eukaryotic viruses to unambiguously assign reads to viral species more accurately and >1000 fold faster than other existing approaches. We validated ViromeScan on synthetic microbial communities and applied it on metagenomic samples of the Human Microbiome Project, providing a sensitive eukaryotic virome profiling of different human body sites. ViromeScan allows the user to explore and taxonomically characterize the virome from metagenomic reads, efficiently denoising samples from reads of other microorganisms. This implies that users can fully characterize the microbiome, including bacteria and viruses, by shotgun metagenomic sequencing followed by different bioinformatic pipelines.


Nonmineralized and mineralized compartments of bone: the role of pyridinoline in nonmineralized collagen.
Collagen tryptic peptides obtained from the nonmineralized and mineralized compartments of diaphyseal bone have different distributions of intermolecular crosslinks. Pyridinoline, a collagen crosslink thought to be associated with chronologically older bone, was detected in peptides from nonmineralized collagen but not from mineralized collagen. Mineralization may prevent collagen maturation; conversely, pyridinoline in nonmineralized collagen may decrease the intermolecular distances among collagen chains in fibrils and preclude mineralization.


MAINE: a web tool for multi-omics feature selection and rule-based data exploration.
Patient multi-omics datasets are often characterized by a high dimensionality; however, usually only a small fraction of the features is informative, that is change in their value is directly related to the disease outcome or patient survival. In medical sciences, in addition to a robust feature selection procedure, the ability to discover human-readable patterns in the analyzed data is also desirable. To address this need, we created MAINE-Multi-omics Analysis and Exploration. The unique functionality of MAINE is the ability to discover multidimensional dependencies between the selected multi-omics features and event outcome prediction as well as patient survival probability. Learned patterns are visualized in the form of interpretable decision/survival trees and rules. MAINE is freely available at maine.ibemag.pl as an online web application. Supplementary data are available at Bioinformatics online.


Synthesis and biological evaluation of benzofuran piperazine derivatives as potential anticancer agents.
This work describes about the synthesis and evaluation of substituted benzofuran piperazines as potential anticancer agents. The synthesized candidates have been evaluated for their cell proliferation inhibition properties in six murine and human cancer cell lines. In vitro evaluation of apoptosis and cell cycle analysis with the lead candidate 1.19 reveals that necrosis might be an important pathway for the candidate compounds to cause cell death. Further, in vivo evaluation of the lead compound shows that this candidate is well tolerated in healthy mice. Additionally, an in vivo anticancer efficacy study in mice using a MDA-MB-231 xenograft model with the lead compound provides good anti-cancer efficacy.


Signal transduction in wound pharmacology.
Growth factors such as TGF-beta, PDGF and FGF are thought to play important roles in wound healing. However, their biological activity and signal transduction during wound repair remain poorly understood. Growth factors are often ligands for receptor tyrosine kinase and receptor serine/threonine kinases. With recent advances in signal transduction by receptor kinases, we are beginning to understand the underlying mechanism of how growth factors may regulate cutaneous wound repair. In this paper, we will describe the pharmacological effects of growth factors on wound healing, and discuss the potential underlying signaling mechanisms. Thus, we hope to provide the basis for designing more specific therapeutics for wound healing in the near future.


Vision loss under silicone oil tamponade.
We aimed to investigate frequency, time course and pathophysiology of vision loss in eyes with macula-on rhegmatogenous retinal detachment operated with vitrectomy and silicone oil tamponade. Fifteen eyes of 15 patients who had been operated with 5,000 centistoke silicone oil between 2006 and 2014 were included in a retrospective case series. Examinations included logMAR best corrected visual acuity (BCVA), visual field testing (VF), spectral domain optical coherence tomography (OCT), electrophysiology, and fluorescein angiography. Vision loss was seen in eight (53 %) eyes of 15 patients with symptomatic central scotoma, which was confirmed by VF (5/6). Preoperative median BCVA of these patients was 0.15 (0.5 to 0), prior to oil removal 0.7 (1.0 to 0.5), and 6 weeks post oil removal 1.0 (1.5 to 0.2). BCVA recovered in five patients to a median of 0.15 (0.5 to 0.1), and it remained 1.0 in three (20 %) out of 15 eyes. OCT revealed significant thinning of the foveal and parafoveal combined nerve fiber, ganglion cell and inner plexiform layers in affected eyes (mean 58.3 μm +/-13, horizontal scan through fovea, 500 μm radius) compared to their healthy fellow eyes (mean 84.5 μm +/-12.3; p < 0.01, n = 6 patients, 12 eyes) and compared to eyes with no vision loss under silicone oil. We find persisting vision loss in three out of 15 patients treated for macula-on rhegmatogenous retinal detachment with silicone oil tamponade. Thinning of inner retinal layers possibly evoked by silicone oil tamponade might be a pathophysiological explanation for vision loss in these patients.


Methionine restriction-induced sulfur deficiency impairs antitumour immunity partially through gut microbiota.
Restriction of methionine (MR), a sulfur-containing essential amino acid, has been reported to repress cancer growth and improve therapeutic responses in several preclinical settings. However, how MR impacts cancer progression in the context of the intact immune system is unknown. Here we report that while inhibiting cancer growth in immunocompromised mice, MR reduces T cell abundance, exacerbates tumour growth and impairs tumour response to immunotherapy in immunocompetent male and female mice. Mechanistically, MR reduces microbial production of hydrogen sulfide, which is critical for immune cell survival/activation. Dietary supplementation of a hydrogen sulfide donor or a precursor, or methionine, stimulates antitumour immunity and suppresses tumour progression. Our findings reveal an unexpected negative interaction between MR, sulfur deficiency and antitumour immunity and further uncover a vital role of gut microbiota in mediating this interaction. Our study suggests that any possible anticancer benefits of MR require careful consideration of both the microbiota and the immune system.


Neuroprotection and protein damage prevention by estradiol replacement in rat hippocampal slices exposed to oxygen-glucose deprivation.
Here we investigated the effects of estradiol replacement in ovariectomized female rats using hippocampal slices exposed to oxygen-glucose deprivation (OGD). OGD induced lactate dehydrogenase (LDH) release to the incubation medium, what was assumed as a parameter of cellular death. In the estradiol-treated group the LDH release was markedly decreased by 23% as compared to the vehicle-treated group. In attempt to study a possible mechanism by which estradiol acts, we investigated some parameters of oxidative stress. In both vehicle-treated and estradiol-treated groups, OGD significantly increased the free radical production by 34% and 16%, respectively, although no significant differences on total antioxidant capacity were observed. Interestingly, estradiol replacement prevented the significant reduction in tryptophan and tyrosine contents caused by OGD observed in vehicle-treated animals. Our results show that estradiol replacement in ovariectomized female rats decreases cellular susceptibility to an ischemic-like injury and suggest a role for the hormone on protein damage prevention.


Attachment anxiety, relationship context, and sleep in women with recurrent major depression.
To examine the relationship between attachment anxiety, marital status, bed-partner status, and sleep in recurrently depressed women. The current study measured polysomnography (PSG) and subjective sleep quality in 107 women with recurrent major depression. Women were categorized as high or low in attachment anxiety based on Bartholomew and Horowitz's Relationship Questionnaire (1991). There were no significant main or interaction effects of any of the relationship measures on subjective sleep quality. In contrast, PSG results indicated that women with bed partners displayed better sleep efficiency (p < .005). Marital status was also associated with sleep efficiency (p < .05), and married women displayed significantly shorter sleep latencies as compared with never married women (p < .05). Anxiously attached women displayed a reduced percentage of stage 3-4 sleep (p < .05). Moreover, a significant interaction between attachment anxiety and marital status (p < .05) suggested that anxiously attached women who were previously married (i.e., divorced, separated, or widowed) displayed a particularly low percentage of stage 3-4 sleep. Depressed women who exhibit an anxious attachment style and have experienced a marital rupture show reduced stage 3-4 sleep, which may signal a concomitant reduction in restorative cognitive and metabolic processes. Relationship context influences sleep continuity. These results provide a more nuanced approach to considering qualitative and structural aspects of relationships that may influence sleep.


The chemistry and biology of thymosin. I. Isolation, characterization, and biological activities of thymosin alpha1 and polypeptide beta1 from calf thymus.
A partially purified extract from thymus tissue termed thymosin Fraction 5 has been shown to reconstitute immunological deficiencies resulting from the lack of thymic function in several animal models, as well as humans with primary and secondary immunodeficiency diseases. Thymosin Fraction 5 consists of a family of polypeptides with molecular weights ranging from 1,000 to 15,000. Several of these polypeptides contribute individually to the biological activity of the parent compound. Two polypeptide components of thymosin Fraction 5, termed thymosin alpha1 and polypeptide beta1, have been characterized chemically and biologically. Thymosin alpha1 is a highly acidic molecule composed of 28 amino acid residues. This polypeptide has potent biological activity and has been found to be 10 to 1,000 times as active as thymosin Fraction 5 in one in vivo and several in vitro bioassay systems designed to measure differentiation and function of thymus-dependent lymphocytes (T cells). Polypeptide beta1, in contrast, is inactive in our bioassay systems, suggesting that it is not involved in thymic hormone action. Sequence analysis and homology studies have indicated that polypeptide beta1, although present in Fraction 5, does not contribute to the biological activity of thymosin Fraction 5.


Risk profiles and a concise prediction model for lymph node metastasis in patients with lung adenocarcinoma.
Lung cancer is the second most commonly diagnosed cancer and ranks the first in mortality. Pathological lymph node status(pN) of lung cancer affects the treatment strategy after surgery while systematic lymph node dissection(SLND) is always unsatisfied. We reviewed the clinicopathological features of 2,696 patients with LUAD and one single lesion ≤ 5 cm who underwent SLND in addition to lung resection at the Sun Yat-Sen University Cancer Center. The relationship between the pN status and all other clinicopathological features was assessed. All participants were stochastically divided into development and validation cohorts; the former was used to establish a logistic regression model based on selected factors from stepwise backward algorithm to predict pN status. C-statistics, accuracy, sensitivity, and specificity were calculated for both cohorts to test the model performance. Nerve tract infiltration (NTI), visceral pleural infiltration (PI), lymphovascular infiltration (LVI), right upper lobe (RUL), low differentiated component, tumor size, micropapillary component, lepidic component, and micropapillary predominance were included in the final model. Model performance in the development and validation cohorts was as follows: 0.861 (95% CI: 0.842-0.883) and 0.840 (95% CI: 0.804-0.876) for the C-statistics and 0.803 (95% CI: 0.784-0.821) and 0.785 (95% CI: 0.755-0.814) for accuracy, and 0.754 (95% CI: 0.706-0.798) and 0.686 (95% CI: 0.607-0.757) for sensitivity and 0.814 (95% CI: 0.794-0.833) and 0.811 (95% CI: 0.778-0.841) for specificity, respectively. Our study showed an easy and credible tool with good performance in predicting pN in patients with LUAD with a single tumor ≤ 5.0 cm without SLND and it is valuable to adjust the treatment strategy.


Efficient removal of dyes and proteins by nitrogen-doped porous graphene blended polyethersulfone nanocomposite membranes.
Nitrogen-doped porous graphene oxide (N-PGO) was synthesized, characterized, and applied as a hydrophilic nanomaterial in fabrication of polyethersulfone (PES) membrane for Reactive Red 195 dye and bovine serum albumin (BSA) protein separation. The N-PGO nanosheets not merely showed a good adhesion towards polymers, but simultaneously promoted hydrogen bonding action. Therefore, high-efficiency permeation passageway in the separation layer of membranes was attained. X-ray photoelectron spectroscopy (XPS), energy dispersive spectroscopy (EDX) and Fourier transform infra-red spectroscopy (FTIR) analyses approved nitrogen doping, which increased hydrophilicity and hydrogen bonding ability of PGO in water filtration. The pure water permeation of nanocomposite membranes could reach as high as 190 L m-2 h-1 at 3 bar. A dye rejection efficiency higher than 92% and BSA rejection higher than 95% were accordingly obtained. Atomic force microscopy (AFM) images approved formation of a rough surface that was decreased by addition of low amounts of the PGO. SEM images provided from the surface also confirmed enlarged pore size and increased porosity. Antifouling properties were investigated by BSA filtration, and results showed that the flux recovery ratio of the N-PGO membrane was improved. Overall, the N-PGO hybrid membranes exhibited potential for application in separation of typical proteins and dyes with good antifouling properties.


Differential Analysis of 2-D Maps by Pixel-Based Approaches.
Two approaches to the analysis of 2-D maps are available: the first one involves a step of spot detection on each gel image; the second one is based instead on the direct differential analysis of 2-D map images, following a pixel-based procedure. Both approaches strongly depend on the proper alignment of the gel images, but the pixel-based approach allows to solve important drawbacks of the spot-volume procedure, i.e., the problem of missing data and of overlapping spots. However, this approach is quite computationally intensive and requires the use of algorithms able to separate the information (i.e., spot-related information) from the background. Here, the most recent pixel-based approaches are described.


Can thyroxine halt the progression of peripheral arterial disease?
Fifteen women with claudication and increased serum thyrotrophin (TSH) were treated with L-thyroxine (25-75 micrograms). These women were selected from a group of 80 consecutive women presenting with claudication, rest pain or gangrene. One year after their TSH was normal, their progress, serum lipids and lipoproteins were compared with the 58 women with normal levels of serum TSH; the remainder were already receiving thyroxine. Non-invasive assessment showed that three of the 15 (20%) women treated with thyroxine had progression of arterial disease, two in the legs and one in the legs and coronary arteries; two women showed improvement of ankle/brachial pressure indices. There was no accelerated angina, myocardial infarction, stroke or death in this group. Fifty-six of the 58 patients with normal levels of TSH were alive at follow-up and there was progression of distal disease in 24 (43%), coronary artery disease in 6 (11%), increasing carotid stenosis in four and two complained of transient ischaemic attacks. In this group, disease progression affected 32/56 (57%) of the women and this is significantly greater than in the thyroxine treated group chi 2 (P less than 0.05). Treatment with L-thyroxine caused a significant increase in HDL-cholesterol from 1.29 +/- 0.34 to 1.45 +/- 0.49 mmol/L (P less than 0.05) and a significant decrease in cholesterol from 8.0 +/- 1.3 to 7.2 +/- 1.1 mmol/L (P less than 0.01) and apolipoprotein B from 1.23 +/- 0.20 to 1.04 +/- 0.16 g/l (P less than 0.001). Significant changes in apolipoprotein B were observed after 3 months of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Growth factors that repress myoblast differentiation sustain phosphorylation of a specific site on histone H1.
A monoclonal antibody (12D11) is presented that binds an epitope on histone H1 only when it is phosphorylated. Skeletal myoblasts, which are cultured in high mitogen medium to induce proliferation and inhibit differentiation, contain histone H1 reactive with monoclonal antibody 12D11, whereas differentiated myocytes and adult skeletal muscle do not. Phosphorylation of H1 at the 12D11 epitope, as assessed by antibody binding, is also induced and maintained in myoblasts cultured in low mitogen medium supplemented with transforming growth factor beta, which blocks differentiation but allows the cells to withdraw from the cell cycle (Olson, E., Sternberg, E., Hu, J., Spizz, G., and Wilcox, C. (1986) J. Cell Biol. 103, 1799-1805; Massague, J., Cheipetz, S., Endo, T., and Nadal-Ginard, B. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 8206-8210). These observations suggest that phosphorylation of histone H1 at the 12D11 epitope is associated with the negative regulation of myoblast differentiation by growth factors.


[2-frequency artificial respiration--a new therapeutic concept].
A new respiration system is described. The system has been developed for the therapy of very ill newborn and premature infants (RDS stage IV, gestation age less than 28 weeks, severe pneumonia etc.). The special feature of the new respiratory device is an alternating between cycles with low frequencies and relatively high amplitudes, and breathes with low amplitudes and relatively high frequencies.


Environmental fate of chlorpyrifos.
Chlorpyrifos is an organophosphorus compound that displays broad-spectrum insecticidal activity against a number of important arthropod pests. As a result, it is employed in a wide variety of agricultural and specialty pest control scenarios. Various formulations of chlorpyrifos have been developed to maximize stability and contact with pests and minimize human exposure. From corn agriculture in the United States to termite control in Japan to cotton agriculture in Egypt to citrus horticulture in Spain, chloropyrifos has been successfully employed to combat insect and other arthropod pests threatening the production of food and fiber and maintenance of human health. Due to the nonpolar nature of the chlorpyrifos molecule, it possesses a low water solubility (< 2 ppm) and great tendency to partition from aqueous into organic phases in the environment (log P of 4.7-5.3). It is characterized by an average soil and sediment sorption coefficient (Koc) of 8498 and aquatic bioconcentration factor of 100-5100 in fish. As a result of its high propensity for sorption, its movement through and over the soil profile is limited. It has been found to be relatively immobile vertically in soil and has not proved to be a groundwater contaminant. Surface runoff and erosion mobility are also low, and, in general, less than 0.3% of soil surface application has been observed to move even under the heaviest simulated precipitation conditions. Chlorpyrifos has an intermediate vapor pressure (2 x 10(-5) mm Hg, 25 degrees C), and under some conditions volatility is a significant mechanism of dissipation. This is especially true for plant foliage, from which it is the major means of loss, to some extent from water surfaces, and to a lesser degree from moist soil surfaces. Chlorpyrifos is a degradable compound, and both abiotic and biotic transformation processes effect its degradation within environmental compartments (Fig. 1). In all cases, the major pathway of transformation involves cleavage of the phosphate ester bond to form 3,5,6-trichloro-2-pyridinol (TCP). Hydrolytic transformation, although relatively slow in pure water under ideal conditions (half-lives of 29-74 d at pH 7, 25 degrees C), may be catalyzed under certain environmental conditions. These include alkaline conditions in water (pH > or = 8) and alkaline (pH > or = 7.5) and air-dry conditions in soil, and in some soils hydrolysis may be the major means of dissipation (Fig. 2).(ABSTRACT TRUNCATED AT 400 WORDS)


[Acne, pregnant women and zinc salts: a literature review].
Acne in adult women is a common reason for dermatological consultation. Dermatologists are occasionally confronted with the problem of treating acne in women who are either pregnant or seeking to become pregnant, or in breast-feeding women, in whom zinc salts are the only form of systemic treatment that may be envisaged. The purpose of our study was to provide an overview of existing data concerning the use of the zinc salts in pregnant and breast-feeding women based on a literature review, a survey of prescription of zinc gluconate by French dermatologists, and finally, analysis of French pharmacovigilance data. There are many studies involving the use of zinc supplements during pregnancy. In these studies, more than 2500 pregnant women were given zinc at different doses. None of these studies described any abnormalities, congenital malformation, harmful effects or risk for the foetus associated with the use of zinc during pregnancy at doses below 75 mg/day. Although there are fewer studies of the use of zinc supplements in breast-feeding women, no abnormalities associated with use of zinc during breast-feeding have been reported. According to the results of the prescription survey, around 10,000 pregnant women and 2000 breast-feeding women are treated each year for acne using zinc gluconate, with only four serious adverse events involving zinc being reported since the initial introduction of the product, and with zinc having a doubtful causal relationship. Zinc plays a key role in our body's physiology, since it is involved in the activities of many enzymes. In addition, zinc requirements increase during pregnancy, mainly because of its utilisation during embryogenesis and fetal development. This literature review shows that use of zinc salts in pregnant women is beneficial in those with zinc deficiency but that it has no harmful effects in those without zinc deficiency.


Resection of Quadrigeminal Midbrain Cavernous Malformation Using the Supracollicular Safe Entry Zone.
Brainstem cavernous malformations (BSCMs) are rare and challenging neurosurgical lesions that demand a sophisticated and nuanced strategy for resection. A key element of surgical planning for BSCM resection is brainstem safe entry zones, a set of neuroanatomically defined locations where a pial resection can be executed with minimal risk to the adjacent central nervous system tracts and nuclei.1-5 Quadrigeminal BSCMs are particularly unusual and can be accessed via the supra-, inter-, or infracollicular safe entry zones.2,4,5 We report a unique demonstration of the supracollicular safe entry zone for the resection of a symptomatic hemorrhagic quadrigeminal plate BSCM. A man in his early 60s presented with transient hearing loss and visual dysfunction. A right quadrigeminal midbrain cavernous malformation was identified on magnetic resonance imaging. Surgical resection was performed with the patient in the sitting position. A bipedicular suboccipital flap, torcular craniotomy, and midline supracerebellar infratentorial approach were used. The lesion itself was accessed via the supracollicular safe entry zone, where pial hemosiderin staining was also encountered, using a linear transverse incision just above the right superior colliculus. Gross total resection was achieved, and the patient recovered from surgery with no new neurologic deficits (Video 1).


Niemann-Pick diseases.
The Niemann-Pick disease group is now divided into two distinct entities: (1) acid sphingomyelinase-deficient Niemann-Pick disease (ASM-deficient NPD) resulting from mutations in the SMPD1 gene and encompassing type A and type B as well as intermediate forms; (2) Niemann-Pick disease type C (NP-C) including also type D, resulting from mutations in either the NPC1 or the NPC2 gene. Both Niemann-Pick diseases have an autosomal recessive inheritance and are lysosomal lipid storage disorders, with visceral (type B) or neurovisceral manifestations. The clinical knowledge is updated taking into account recent surveys in large cohort of patients, particularly for type B and type C. The diagnosis of NP-C is often delayed due to the wide spectrum of clinical phenotypes. Systemic manifestations, if present, always precede onset of neurological manifestations. Most common neurological signs are vertical supranuclear gaze palsy, cerebellar ataxia, dysarthria, dysphagia, and progressive dementia. Cataplexy, seizures, and dystonia are other common features of NP-C. For both ASM-deficient NPD and NP-C, strategies for laboratory diagnosis of patients and prenatal diagnosis are discussed. Recent progress towards enzyme replacement therapy in type B patients and management of the neurological disease in type C patients are finally highlighted.


Strategies to circumvent the T315I gatekeeper mutation in the Bcr-Abl tyrosine kinase.
Despite the remarkable success of imatinib against Bcr-Abl, development of secondary resistance, most often due to point mutations in the Bcr-Abl tyrosine kinase (TK) domain, is quite common. Of these, the T315I "gatekeeper" mutation is resistant to all currently registered Bcr-Abl TK inhibitors (TKIs) with the notable exception of ponatinib (Iclusig™), which was very recently approved by the United States Food and Drug Administration (FDA). Besides ponatinib, numerous strategies have been developed to circumvent this problem. These include the protein synthesis inhibitor omacetaxine (Synribo®), and "switch-control" inhibitors. Dual Bcr-Abl and aurora kinase inhibitors represent another promising strategy. Finally, several promising synergistic combinations, such as TKIs with histone deacetylase inhibitors (HDACIs), warrant attention.


Impaired granulocyte adherence. A reversible defect in host defense in patients with poorly controlled diabetes.
When the ability of granulocytes from 10 poorly controlled diabetic patients with fasting hyperglycemia and no evidence of ketoacidosis (mean fasting glucose 293 +/- 20 mg. per 100 ml.; mean +/- S.E.M.) to adhere to a nylon fiber column was assessed, the number of adherent granulocytes from whole blood was only 53 +/- 6 per cent of the values observed in controls. After antidiabetic treatment for one to two weeks and lowering of fasting glucose levels (mean 198 +/- 29 mg. per 100 ml.), adherence improved significantly (p less than 0.01) in the diabetics; however, their values were still subnormal (diabetic 74 per cent +/- 8 of control; p less than 0.02). Adherence values before and after treatment correlated with the fasting glucose level (r = 0.88, p less than 0.001). These findings suggest that, in addition to previously reported abnormalities in migration and the ingestion and killing of bacteria, granulocyte adherence may also be impaired in poorly controlled diabetic patients. This functional abnormality correlates directly with the fasting glucose and is reversed by insulin treatment. A defect of this type may compromise the normal inflammatory response in some diabetics and impair their capacity to resist infection.


Effect of repeated radiofrequency catheter ablation on left atrial function for the treatment of atrial fibrillation.
Radiofrequency catheter ablation (RFCA) is a potential curative treatment for atrial fibrillation (AF) by eliminating the arrhythmia and inducing left atrial (LA) reverse remodeling. However, the effect on LA function, especially after repeated procedures, has scarcely been studied. The aim of this study was to evaluate the impact of RFCA on LA size and function in patients with AF after a first and a repeated procedure. RFCA was performed in 154 patients with symptomatic drug-refractory AF. LA volumes and function were assessed with real-time 3-dimensional echocardiography before and 6 months after the procedure. Recurrence of the arrhythmia was defined as any atrial tachyarrhythmia lasting >30 seconds, clinically documented or by 24-hour Holter recording, after the first 6 months after ablation. Of the 154 patients, 104 (67%) required only a first ablation, and 50 (33%) required redo RFCA. LA volume was reduced after first RFCA (from 60 ± 19 to 52 ± 17 ml for 3-dimensional LA maximum volume, p <0.001, and from 38 ± 18 to 33 ± 15 ml for 3-dimensional LA minimum volume, p <0.000) without impairment of LA contractile function, measured as the active emptying percentage of total volume (39 ± 25% vs 43 ± 26%, p = NS). After repeated RFCA procedures, 3-dimensional LA maximum volume was reduced (from 57 ± 18 to 52 ± 18 ml, p = 0.04), also without further LA contractile function impairment (active emptying percentage of total volume) (36 ± 24% vs 36 ± 25% of total volume, p = NS). This effect was similar in paroxysmal and persistent AF. In conclusion, RFCA induces reductions in LA volumes without a deleterious impact on contractile function, even after repeated ablation.


Use of computed radiography in respiratory distress syndrome in the neonatal nursery.
A study was performed to establish the value of a computed radiography (CR) system in neonatal respiratory distress syndrome (RDS). CR images obtained with various X-ray doses were compared with the images of a standard film-screen system. The image quality of CR taken with about one half radiation exposure, was comparable to that of the standard high speed film-screen combination. The use of CR could lead to a significant reduction in radiation in the neonatal I.C.U.


The effect of long-term alcohol intake on brain NGF-target cells of aged rats.
It was reported that chronic exposure to ethanol causes a loss of hippocampal pyramidal cells and of brain cholinergic neurons in both laboratory animals and humans. In the present study, it was hypothesized that nerve growth factor (NGF), a trophic agent for the survival and maintenance of basal forebrain cholinergic neurons (FCN), might be affected by the neurodegenerative events which occur during ethanol consumption. To test this hypothesis, we used aged rats (14 months) exposed for 16 weeks to 40 g/kg per day of undiluted wine. Our experiments showed that chronic alcohol consumption causes a reduction of NGF in the hippocampus (HI) and of choline acetyltransferase (ChAT) activity in both the septum and the HI and a reduction in the distribution of NGF-receptors (NGF-R) in the septum and nucleus of Meynert. Intracerebral injection of NGF in alcohol-exposed rats results in a return to normal levels of ChAT enzymatic activity and NGF-R expression. These experiments indicate that the damaging effect of alcohol on the FCN is also associated with impairment of central NGF-target structures.


Chemiluminescent ELISA with multi-epitope proteins to improve the diagnosis of canine visceral leishmaniasis.
Diagnosing canine visceral leishmaniasis (CVL) is difficult because clinical signs of the disease are non-specific and a many infected animals in endemic areas, as in Brazil, are asymptomatic. Serological tests are the most common diagnostic methods employed, but most have limitations. For this reason, the implementation of a rapid, sensitive, and specific diagnostic test for CVL has become increasingly important. In this study, we adapted a chemiluminescent enzyme-linked immunosorbent assay (CL ELISA), using two multi-epitope recombinant proteins (PQ10 and PQ20) and a crude Leishmania antigen produced using promastigotes of L. infantum, as antigens to detect CVL infection in animals from Belo Horizonte. To investigate cross-reactions, samples from dogs with other infections (babesiosis, ehrlichiosis and Trypanosoma cruzi) were tested. Assay performance validations were conducted to analyse parameters such as variability, reproducibility, and stability. CL ELISA sensitivity/specificity with PQ10 antigen was 93.1%/80.0%; with the PQ20 protein 93.1%/96.6%; and with the crude antigen 75%/73.3%. Inter-assay variability and inter-operator coefficient of variation were <7% and <15%, with PQ10 and PQ20, respectively. The accuracy of the CL ELISA was classified as excellent for PQ10 (AUC = 0.95) and PQ20 (AUC = 0.98) and moderate for the crude antigen (AUC = 0.77). The kappa score for qualitative agreement between two plate lots was excellent for PQ10 (0.89) and good for PQ20 (0.65). PQ20 remained more stable than PQ10. The CL ELISA with recombinant proteins is a promising tool to diagnose CVL.


[Therapeutic response evaluation by nuclear functional imaging].
Nuclear functional imaging is a reliable technique for the early evaluation of conventional cytotoxic and cytostatic agents. It also represents a major tool for the development and validation of anti-tumor targeted therapies.


[Capecitabine].
Capecitabine, an oral fluoropyrimidine carbamate, is adopted worldwide. As the treatment for metastatic colorectal cancer, capecitabine showed at least comparable efficacy with a favorable safety profile to bolus 5-FU/LV. In a large phase III trial (Xeloda Adjuvant Chemotherapy Trial: X-ACT), as the adjuvant treatment of patients with resected stage III colon cancer, capecitabine showed at least comparable disease-free survival, overall survival, and relapse-free survival with a favorable safety profile to bolus 5-FU/LV. Additionally, capecitabine-based combination regimens with oxaliplatin or irinotecan are now under evaluation. In phase II studies, capecitabine has shown the promising results in combination therapy. In Japan, capecitabine has been evaluated since 1994. In a recent phase II study, which evaluated the global dose as first-line treatment for metastatic colorectal cancer, the response rate was 35% (95% CI 23.1-48.4). The median time to disease progression was 169 days and the median overall survival was 617 days. Hand-foot syndrome (HFS), a characteristic adverse event of capecitabine, was observed in 73.3% of the patients, but the grade 3/4 was observed in 13.3% of the patients and only one patient discontinued the treatment due to HFS. An immediate approval of capecitabine in Japan is expected.


What Have Games Got to Do with Me?
Is the proliferation of work-based games just a distraction, or can they actually help us to acquire work-specific knowledge? This Opinion explains why we can see the benefits of such games, despite initial skepticism. Players learn from listening to and observing others, and some people even enjoy the games.


Outcome of declined neonatal surgical referrals at Cairo University Specialized Pediatric Hospital.
The combination of a high birth rate and limited resources leads to a strain on health services with dire consequences to the patient. This study aimed to track the outcome of declined referrals at the tertiary center in the Cairo University Specialized Pediatric hospital. Data were collected prospectively on all declined surgical neonates at the tertiary center. The families were later contacted to document outcomes. Verbal consent was taken. Over a 12 month period from January 2017 to December 2017, 668 neonatal surgical referrals were received. Of these 278, (41·6%) were declined for lack of available places. The majority were cases of esophageal atresia with tracheoesophageal fistula (35%), followed by bowel obstruction (21%). Thirty-six cases were lost to follow up. Of the remaining 242 cases, 103 (42·5%) died, 63 (26%) were referred to public hospitals, 69 (28·5%) to private hospitals and seven (2·8%) were managed conservatively. Nearly half of neonatal surgical cases die while waiting for surgical intervention. Cases were shared equally between the public and private sector. The collected data are crucial in planning service provision for neonates requiring surgical treatment. To the best of our knowledge, this is the first study from Egypt and the region to report the number and outcome of surgical neonates who do not get access to expert surgical services. The study outlines the burden of disease faced by a single pediatric surgery unit and documents the various congenital anomalies encountered as well as their outcome when treated elsewhere. Prognosis study. IV.


Treewidth-based algorithms for the small parsimony problem on networks.
Phylogenetic reconstruction is one of the paramount challenges of contemporary bioinformatics. A subtask of existing tree reconstruction algorithms is modeled by the SMALL PARSIMONY problem: given a tree T and an assignment of character-states to its leaves, assign states to the internal nodes of T such as to minimize the parsimony score, that is, the number of edges of T connecting nodes with different states. While this problem is polynomial-time solvable on trees, the matter is more complicated if T contains reticulate events such as hybridizations or recombinations, i.e. when T is a network. Indeed, three different versions of the parsimony score on networks have been proposed and each of them is NP-hard to decide. Existing parameterized algorithms focus on combining the number c of possible character-states with the number of reticulate events (per biconnected component). We consider the parameter treewidth t of the underlying undirected graph of the input network, presenting dynamic programming algorithms for (slight generalizations of) all three versions of the parsimony problem on size-n networks running in times [Formula: see text], [Formula: see text], and [Formula: see text], respectively. Our algorithms use a formulation of the treewidth that may facilitate formalizing treewidth-based dynamic programming algorithms on phylogenetic networks for other problems. Our algorithms allow the computation of the three popular parsimony scores, modeling the evolutionary development of a (multistate) character on a given phylogenetic network of low treewidth. Our results subsume and improve previously known algorithm for all three variants. While our results rely on being given a "good" tree-decomposition of the input, encouraging theoretical results as well as practical implementations producing them are publicly available. We present a reformulation of tree decompositions in terms of "agreeing trees" on the same set of nodes. As this formulation may come more natural to researchers and engineers developing algorithms for phylogenetic networks, we hope to render exploiting the input network's treewidth as parameter more accessible to this audience.


The child with asthma at school: results from a national asthma survey among schoolchildren in Israel.
To evaluate school absence and restriction in school activities of children with asthma, and to estimate the involvement of the school staff in asthma disabilities. A modified version of the International Study of Asthma and Allergies in Childhood written questionnaire was administered to a national sample of 13-14-year-old schoolchildren across Israel. Questions regarding social and demographic factors, school absence owing to asthma symptoms, and school staff involvement were added. There were 10,057 complete questionnaires available for analysis; 710 children reported having asthma. Children with asthma were absent on the average 7.3 +/- 9.8 days in the past school year compared with 3.9 +/- 6.3 days in children without (p = .0001). Absenteeism owing to respiratory symptoms was significantly more common in children with asthma and associated with a more severe asthmatic condition. Four percent of the children with asthma were absent from school more than 30 days. Of the children reporting asthma, 25.9% were not allowed to participate in one or more school activities for medical reasons, compared with 4.2% of children without asthma. Of the children with asthma, 44.3% reported that the school nurse knew about their asthma, and only 13.8% reported that the nurse discussed their asthmatic condition with them; 38.2% of children with asthma reported that no one at school knew about their illness. Children with asthma are absent annually on average 3.4 days more than children without asthma. School absence is associated with the severity of asthma. A significant percentage of asthmatic children participate less in school activities. School staff awareness of the children illness is not satisfactory.


Associations between the major histocompatibility complex class I chain-related gene A transmembrane (MICA-TM) polymorphism and susceptibility to psoriasis and psoriatic arthritis: a meta-analysis.
The aim of this study was to assess whether the major histocompatibility complex class I chain-related gene A transmembrane (MICA-TM) polymorphism is associated with the susceptibility to psoriasis and psoriatic arthritis (PsA). A meta-analysis was conducted to establish the association between the MICA-TM A9 allele and psoriasis and PsA in the general population and each ethnic group. Ten studies (6 psoriasis, 4 PsA) involving 2,002 cases and 1,933 controls were included in this meta-analysis. The Asian controls showed the lowest A9 allele prevalence (16.6%), whereas the European controls had the highest allele prevalence (33.3%). Meta-analysis revealed a significant association between the MICA-TM A9 allele and the entire study population, which included the psoriasis and PsA cases (OR 1.703; 95% CI 1.301-2.229; p = 1.0 × 10(-5)). We further divided the entire study population into the psoriasis and PsA groups. Meta-analysis revealed a significant association between the MICA-TM A9 allele and the entire study population (OR 1.427, 95% CI 1.021-1.994; p = 0.037) and Asians (OR 1.264; 95% CI 1.014-1.576; p = 0.037). A significant association was found between the MICA-TM A9 allele and PsA (OR 2.227; 95% CI 1.462-3.393; p = 1.9 × 10(-5)) and Europeans (OR 2.039; 95% CI 1.285-3.235; p = 0.002). This meta-analysis showed that the MICA-TM A9 allele is associated with psoriasis susceptibility in Asian populations and that the MICA-TM A9 allele is associated with a PsA risk in Europeans.


Trajectories and Predictors of Symptoms of Depression in Chinese Women From Early Pregnancy to the Early Postpartum Period.
To explore the trajectories and predictors of symptoms of depression in Chinese women from early pregnancy to 3 months after birth. Prospective cohort study. Several maternal and child health care institutions and obstetric departments of general hospitals in Beijing, Jiangsu, Hunan, Sichuan, Shandong, Guangdong, and Shanxi provinces in China. Chinese women (N = 667) during pregnancy and the postpartum period. From August 2019 to June 2020, participants from several tertiary hospitals in China who completed at least three measurements during early pregnancy to 3 months after birth (from time point 1 to time point 5) were included for data analysis. We used the self-administered basic information questionnaire and the Edinburgh Postnatal Depression Scale for follow-up. We used Mplus version 8.3 to construct the growth mixture modeling and SPSS version 25.0 to carry out logistic regression analysis. We found three potential trajectories of symptoms of depression during pregnancy and the postpartum period: the down-then-up healthy group (Class 1, 68.5%), steady-growth moderate-risk group (Class 2, 27.5%), and up-then-down high-risk group (Class 3, 4.0%). Multinomial logistic regression analysis showed that being pregnant for the first time, being a company employee, being less satisfied with the living environment, and the occurrence of negative life events were significant predictors of the Class 2 trajectory, whereas younger age, being less satisfied with food, and the occurrence of negative life events were predictors of the Class 3 trajectory. The trajectories of symptoms of depression during pregnancy and the postpartum period among Chinese women showed significant group heterogeneity. The trajectory categories were influenced not only by demographics and pregnancy-related factors but also by maternal subjective feelings.


Content uniformity in granules for aceclofenac controlled release (CR) tablets determined using near-infrared spectroscopy and wide area illumination (WAI) Raman spectroscopy.
Non-destructive and rapid determination methods were developed for aceclofenac controlled release (CR) tablets. The tablet is composed of two layers, rapid release and controlled release (CR) layers. The pharmaceutical manufacturing process for CR granules is very critical for dissolution control of CR tablets. During processing, a rapid and nondestructive method to test content uniformity of aceclofenac granules is required. Chemometrics using near-infrared (NIR) and Raman spectroscopy have found significant uses in quantitative analysis of pharmaceutical products in complex matrixes. Most of the pharmaceutical products can be measured directly with little or no sample preparation using these spectroscopic methods. This study showed NIR and wide area illumination Raman spectroscopy with partial least squares (PLS) was very effective for the content uniformity of granules while high performance liquid chromatography (HPLC), a conventional method, was time-consuming and ineffective for real time control. This study showed that on-line control of content uniformity control of aceclofenac CR tablets can be achieved using NIR and Raman spectroscopy.


A conformationally constrained inhibitor with an enhanced potency for β-tryptase and stability against semicarbazide-sensitive amine oxidase (SSAO).
A novel β-tryptase inhibitor with a basic benzylamine P1 group, a piperidine-amide linker, and a substituted indole P4 group was discovered. A substitution at 4-indole position was introduced to constrain the conformational flexibility of the inhibitor to the bioactive conformation exhibited by X-ray structures so that entropic penalty was decreased. More importantly, this constrained conformation limited the accessibility of this molecule to anti-targets, especially SSAO, so that an enhanced metabolic profile was achieved.


A comparison of two endoscopic closures: over-the-scope clip (OTSC) versus KING closure (endoloop + clips) in a randomized long-term experimental study.
Both over-the-scope clip (OTSC) and KING (endoloop + clips) closures provide reliable and safe full-thickness endoscopic closure. Nevertheless, OTSC clip demonstrated significantly inferior histological healing in the short-term follow-up. To compare OTSC versus KING closure of a perforation with regard to long-term effectiveness and macroscopic and histological quality of healing. We performed a randomized experimental study with 16 mini-pigs (mean weight 43.2 ± 11.2 kg). A standardized perforation was performed on the anterior sigmoid wall. KING closure (n = 8) was attained by approximation of an endoloop fixed to the margins of a perforation with endoclips. OTSC closure (n = 8) was performed by deploying OTSC (OVESCO) over the defect. Pigs underwent a control sigmoidoscopy 8 months after the closure to assess the macroscopic quality of healing. Then, autopsy was performed and the rectosigmoid was sent for histopathological assessment. All closures were completed successfully without air leaks. The duration of closure was similar in both techniques (OTSC 17.8 ± 7.6 min vs. KING 19.6 ± 8.8 min). At autopsy, all KING closures (100 %) were healed with a flat scar without signs of leakage. Microscopically, no inflammatory changes were observed after KING closure. In the OTSC group, microscopic ulcers were present in two pigs (25 %), cryptal abscesses in three pigs (38 %) and significant neutrophil accumulation in all eight pigs (P < 0.01). Giant cell granulomas, dysplasia or abundant scarification was not observed in either group. Both OTSC and KING closures offer a long-term reliable seal of a gastrointestinal perforation without stenosis or fistulas. KING closure provides long-term histologically superior healing.


Quality control of microarray assays for toxicogenomic and in vitro diagnostic applications.
The generation of high-quality microarray data for toxicogenomics can be affected by the study design and methods used for sample acquisition, preparation, and processing. Bias can be introduced during animal treatment, tissue handling, and sample preparation. Metrics and controls used in assessing RNA integrity and the quality of microarray sample generation are reviewed in this chapter. Regulations and guidelines involved in the application of microarrays as a commercial in vitro diagnostic device are also described.


Infectious bursal disease viral infections. I. Complement and virus-neutralizing antibody response following infection of susceptible chickens.
Complement (C) titers were decreased at 3 days postinfection, and virus-neutralizing (VN) antibody was detectable at 3 or 4 days postinfection in chickens with infectious bursal disease virus (IBDV). Clotting times were prolonged in all groups tested during the acute phase of the disease. Mortality appeared to be associated with the severity of decrease in C titer. The results suggest that the mortality and many of the clinical signs seen with infectious bursal disease are associated with: 1) a depletion in circulating levels of hemolytic C from the formation of immune complexes at sites of viral replication; and/or 2) a depletion in some clotting factor which results in hemorrhage.


Maternal and child characteristics associated with mothers' perceptions of their high risk/developmentally delayed infants.
Mothers of 46 high risk infants, many of whom were developmentally delayed, were visited in their homes at approximately 9 months post-expected-date-of-delivery. The Perception of Baby Temperament (PBT) scales and the Profile of Mood States were administered and an observation of infant, parent, and parent-infant behavior was made. Infants were most likely to receive higher PBT scores on more than one scale if their mothers were more highly educated and reported lesser degrees of depression and anxiety. Infants who were perceived as more active and approaching by their mothers tended to be rated as more responsive by the observer and to show less developmental delay. Mothers who rated their infants as more active tended to show greater responsiveness to the infant and to participate in reciprocal activities with the infant more frequently during the home visit. These findings demonstrate that mothers' perceptions of high risk/developmentally delayed infant temperament are associated with similar categories of variables found to correlate with maternal perceptions of developmentally normal infant temperament.


Combined use of chemically modified nucleobases and nanostructured DNA for enhanced immunostimulatory activity of CpG oligodeoxynucleotide.
Oligodeoxynucleotide (ODN) containing a cytosine-phosphate-guanine (CpG) motif, or CpG ODN, is considered suitable for treating immune diseases, including allergies. Although the phosphorothioate modification is used to enhance the stability and immunostimulatory activity of CpG ODNs, it is associated with the risk of adverse effects. Construction of nanostructured DNA assemblies, such as tripod- and hexapod-like structured DNAs, tripodna and hexapodna, respectively, were also found to increase this activity. The chemical modification of nucleobases could be another approach for enhancing CpG ODN activity. Here, we examined whether chemically modified nucleobase substitutions can enhance CpG ODN activity by measuring tumor necrosis factor α (TNF-α) release after addition to murine macrophage-like RAW264.7 cells. First, the guanine at the 18th position of phosphodiester CpG 1668 was substituted with several chemically modified guanines, and then the various guanines were substituted. Among all tested substitutions, 15,18-thdG, in which two guanines outside the CpG motif were substituted with the 2-aminothieno[3,4-d]pyrimidine guanine mimic (thdG), was the most effective. Compared to 32P-CpG 1668, 32P-15,18-thdG was taken up more efficiently by the RAW264.7 cells. Then, 15,18-thdG was incorporated into tripodna and hexapodna. 15,18-thdG/tri- or hexapodna induced higher TNF-α release from the RAW264.7 cells than PO CpG 1668/tri- or hexapodna, respectively. These results indicate that the thdG substitution is a useful effective strategy for enhancing the immunostimulatory activity of CpG DNAs in both single stranded and DNA nanostructure forms.


Assessment of open surgical and endovascular management of true hepatic artery aneurysms over 20 years highlights increased rupture risk in females.
True hepatic artery aneurysms (HAAs) are rare but have been associated with a significant risk of rupture and associated mortality. The 2020 release of HAA-specific clinical practice guidelines represented an important step toward management standardization. However, it remains essential to build on the body of evidence to further refine these recommendations. The HAA management and outcomes from a single academic center during a 20-year period were retrospectively reviewed. We identified 72 patients from the institutional radiology database (November 24, 1999 to 2019). Pseudoaneurysms were excluded, and 48 patients were found to have had true HAAs. Forty-three HAA patients had sufficient medical records for inclusion in the analysis. Of the 43 patients with HAA included, 65% were male. The mean age was 63 years (range, 22-89 years). Of the HAAs, 72% presented asymptomatically, 16% had ruptured, and 12% were symptomatic at presentation. Most HAAs were of atherosclerotic origin (74%). In addition, 16% of the patients had other visceral aneurysms and 12% had nonvisceral aneurysms on presentation. The mean HAA size overall was 3.3 cm (range, 0.8-10.8 cm), with most being solitary (72%) and involving the common hepatic artery (65%). Rupture was more common in females (40%) and those with vasculitis (67%), with females representing 86% of all patients with rupture. The mean size at intervention was 4.8 cm (21 patients [49%]). Ten patients (23%) had undergone open surgical repair (seven elective and three emergent because of rupture). Eleven patients (26%) had undergone endovascular intervention (64% elective and 36% emergent). Nonoperative management was selected for 22 patients (51%). These patients had a mean HAA diameter of 2.1 cm, and 59% had a life-limiting illness. Of the 18 patients who had been initially monitored for a mean of 3.9 ± 4.1 years, 3 had undergone elective repair and 2 had minimal growth. None of these patients had a subsequently documented rupture. True HAAs are a rare but important clinical phenomenon, with 16% of patients presenting with rupture in this study. Endovascular intervention is a promising alternative to open surgical repair, with no 30-day mortality, and is suitable for ruptured HAAs. Importantly, for the first time, our findings have demonstrated an increased risk of rupture for females, highlighting the need for additional data and ultimately, sex-specific guidelines.


Distribution of acetylcholinesterase in the central nervous system of harvestmen (Arachnida: Opilionida).
Enzyme histochemical technique (Gomori and Koelle methods, reaction product development according to Lewis) was applied on 10 microm frozen sections of formalin-fixed material to demonstrate the distribution of acetylcholinesterase in the central nervous system (CNS) of harvestmen (Opilionida: Phalangiidae). Distinctly positive reactions were confined to the neuropil, showing strong staining especially in protocerebral brain centres (optic lobes, cerebral ganglia), the cheliceral ganglia (stomodeal bridge, afferent tracts), and the connective ring systems of the subesophageal nerve mass. The results obtained are discussed with regard to central coordinative functions of the respective brain parts.


Alcohol drinking and HIV-related risk among men who have sex with men in Chongqing, China.
To estimate the prevalence of any alcohol use and heavy alcohol drinking using the Alcohol Use Disorders Identification Test (AUDIT) and its correlates among men who have sex with men (MSM), a cross-sectional study was conducted among 391 MSM in Chongqing, China to collect data about sociodemographic characteristics, alcohol use, sexual behaviors, and other related factors through a computer-assisted self-administered questionnaire. Heavy alcohol drinking in the past 12 months was defined as an AUDIT-C score ≥ 4. Blood was collected from each potential participant to test for HIV and syphilis status. Twenty three percent of MSM had consumed a drink containing alcohol in the previous year. 7.2% had an AUDIT-C score ≥ 4, defined as heavy alcohol drinkers. 23.5% were unmarried, but planning to marry, who were more likely to report any alcohol drinking (adjusted odds ratio [AOR], 2.38; 95% confidence interval [CI], 1.40-4.06) and to have AUDIT-C scores ≥ 4 (AOR, 3.58; 95% CI, 1.60-8.00). MSM who had used any alcohol in the previous year, and MSM who were heavy alcohol drinkers, were more likely to have had anal sex with male casual partners in the previous 6 months, to have been tested for HIV, and to have decreased scores on the scales of general self-efficacy, increased scores on the scales of stigma and discrimination. Our findings provided further evidence of the associations of any alcohol use and heavy alcohol consumption with HIV-risky behaviors, lowered sense of general self-efficacy, and higher sense of HIV/AIDS-related stigma and discrimination among MSM in the city with the highest HIV epidemic among MSM in China.


The effect of hemodialysis and hemoperfusion on serum valproic acid concentration.
We report a patient with dialysis-induced encephalopathy who was taking divalproex sodium for a seizure disorder. Her serum valproic acid concentration appeared to be in the low therapeutic range at 54 mg/l yet she continued to have seizure activity. The elimination half-life and apparent clearance of valproic acid were the same for both a dialysis and nondialysis day, indicating that hemodialysis/hemoperfusion has little effect on the overall removal of valproic acid from the body.


2-deoxy-D-glucose-induced metabolic stress enhances resistance to Listeria monocytogenes infection in mice.
Exposure to different forms of psychological and physiological stress can elicit a host stress response, which alters normal parameters of neuroendocrine homeostasis. The present study evaluated the influence of the metabolic stressor 2-deoxy-D-glucose (2-DG; a glucose analog, which when administered to rodents, induces acute periods of metabolic stress) on the capacity of mice to resist infection with the facultative intracellular bacterial pathogen Listeria monocytogenes. Female BDF1 mice were injected with 2-DG (500 mg/kg b. wt.) once every 48 h prior to, concurrent with, or after the onset of a sublethal dose of virulent L. monocytogenes. Kinetics of bacterial growth in mice were not altered if 2-DG was applied concurrently or after the start of the infection. In contrast, mice exposed to 2-DG prior to infection demonstrated an enhanced resistance to the listeria challenge. The enhanced bacterial clearance in vivo could not be explained by 2-DG exerting a toxic effect on the listeria, based on the results of two experiments. First, 2-DG did not inhibit listeria replication in trypticase soy broth. Second, replication of L. monocytogenes was not inhibited in bone marrow-derived macrophage cultures exposed to 2-DG. Production of neopterin and lysozyme, indicators of macrophage activation, were enhanced following exposure to 2-DG, which correlated with the increased resistance to L. monocytogenes. These results support the contention that the host response to 2-DG-induced metabolic stress can influence the capacity of the immune system to resist infection by certain classes of microbial pathogens.


Erythropoietin may attenuate lung inflammation in a rat model of meconium aspiration syndrome.
Inflammation is believed to play a key role in the pathophysiology of meconium aspiration syndrome (MAS). The objective was to determine whether the recombinant human Erythropoietin (rhEPO) pretreatment could attenuate meconium-induced inflammation. In this study, 24 ventilated adult male rats were studied to examine the effects of recombinant human EPO (rhEPO) on meconium-induced inflammation. Seventeen rats were instilled with human meconium (1.5 mL/kg, 65 mg/mL) intratracheally and ventilated for 3 hours. rhEPO (1000 U/kg) (n = 9) or saline (n = 8) was given to the animals. Seven rats that were ventilated and not instilled with meconium served as a sham-controlled group. Analysis of the blood gases, interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in blood and bronchoalveolar lavage (BAL) fluid samples, and lung tissue myeloperoxidase levels were performed. Intrapulmonary instillation of meconium resulted in the increase of TNF-α (p = 0.005 and p < 0.001, respectively) and IL-8 concentrations (p < 0.001 and p < 0.001, respectively) in BAL fluid in the EPO + meconium and saline + meconium groups compared with the sham-controlled group. rhEPO pretreatment prevented the increase of BAL fluid IL-1β, IL-6, and IL-8 levels (p < 0.001, p = 0.021, and p = 0.005, respectively), and serum IL-6 levels (p = 0.036). rhEPO pretreatment is associated with improved BAL fluid and serum cytokine levels. Pretreatment with rhEPO might reduce the risk of developing of meconium-induced derangements.