Accumulation of genetic changes during development and progression of hepatocellular carcinoma: loss of heterozygosity of chromosome arm 1p occurs at an early stage of hepatocarcinogenesis.
To investigate cumulative genetic changes during development and progression of hepatocellular carcinoma (HCC), we examined DNAs isolated from 104 tumors for loss of heterozygosity (LOH) at 13 loci on six chromosomal arms and for an increase of copy number ("multiplication") of alleles on 8q, using polymorphic microsatellite markers. A comparison of genetic features with clinicopathological stages of these tumors revealed that LOH on 1p had occurred in tumors at an early stage or with a well-differentiated histological phenotype (8/26; 31%) as well as in tumors at more advanced stages. Genetic alterations on chromosome arms 4q, 8p, 8q, 13q, 16q, and 17p were more often observed in tumors of more advanced stages and poorer differentiation grades. When size was the criterion for comparison, LOH on 1p was observed frequently even in tumors smaller than 2 cm (6/16; 38%), whereas allelic losses on 16q were detected frequently only in larger tumors. These results suggest that the putative tumor suppressor gene(s) assumed to be located on 1p may be involved in an early step of carcinogenesis in liver tissue and that the other genetic alterations examined here may play important roles in progression of HCC.


Implementing and evaluating a diversity, equity, and inclusion resident recruitment strategy.
A recruitment strategy was designed to increase the racial diversity of applicants to the postgraduate year 1 pharmacy program at University of Michigan Health, Michigan Medicine (MM). This article describes MM's diversity, equity, and inclusion (DEI) residency recruitment approach, from conceptualization through implementation, and includes an evaluation of its effectiveness. The report of the American Society of Health-System Pharmacists (ASHP) Task Force on Racial Diversity, Equity, and Inclusion, published in January 2021, provided a foundation for our recruitment approach. The approach consisted of establishing a residency DEI subcommittee, conducting outreach to under-represented students, and reducing bias in the process by amending the application screening rubric. The combination of these efforts resulted in a 5% increase in applicants from pharmacy schools with a high proportion of under-represented minority students. A diverse residency program benefits patients, trainees, and the larger healthcare organization. In addition, incorporating DEI into resident recruitment is required by the new ASHP Accreditation Standard for postgraduate pharmacy residency programs effective July 1, 2023. Evaluation of our recruitment efforts demonstrated targeted recruitment as an effective strategy to increase the diversity of a residency program's applicants. There may be additional barriers not addressed by our interventions to be further explored.


Thiol-disulfide status of patients with cervical cancer.
The evaluation of dynamic thiol-disulfide homeostasis among patients with the cancer of the uterine cervix. The study was conducted in 62 cervical cancer patients and 61 healthy women who had been followed up in an obstetrics and gynecology clinic between September 2018 and April 2020. Serum disulfide, native thiol, total thiol, ischemia modified-albumin, total antioxidant and oxidant capacities, and oxidative stress index values were measured in all participants. The mean plasma disulfide levels of the cervical cancer group was statistically significantly higher than that of the control group (25.79 ± 6.90 μmol/L, 22.31 ± 6.11 μmol/L, respectively) (P = 0.004). Plasma native thiol and total thiol levels were lower in cervical cancer patients (299.27 ± 99.05 μmol/L and 350.86 ± 102.72 μmol/L, respectively) compared to controls, but no statistically significant difference was observed (318.00 ± 93.75 μmol/L and 376.44 ± 98.51 μmol/L, respectively) (P = 0.284, P = 0.161). With respect to the ischemia modified-albumin level, no statistically significant difference was observed between two groups. There were statistically significant positive association between disulfide level and both the stage of cervical cancer (r = 0.278, P = 0.029) and total oxidant capacity level (r = 0.256, P = 0.046). Dynamic thiol-disulfide homeostasis may participate in the pathophysiological mechanisms of cervical cancer and may be a potential biomarker for early identification of cervical cancer in future.


How the known reference weakens the visual oblique effect: a Bayesian account of cognitive improvement by cue influence.
This paper investigates the influence of a known cue on the oblique effect in orientation identification and explains how subjects integrate cue information to identify target orientations. We design the psychophysical task in which subjects estimate target orientations in the presence of a known oriented reference line. For comparison the control experiments without the reference are conducted. Under Bayesian inference framework, a cue integration model is proposed to explain the perceptual improvement in the presence of the reference. The maximum likelihood estimates of the parameters of our model are obtained. In the presence of the reference, the variability and biases of identification are significantly reduced and the oblique effect of orientation identification is obviously weakened. Moreover, the identification of orientation in the vicinity of the reference line is consistently biased away from the reference line (i.e., reference repulsion). Comparing the predictions of the model with the experimental results, the Bayesian Least Squares estimator under the Variable-Precision encoding (BLS_VP) provides a better description of the experimental outcomes and captures the trade-off relationship of bias and precision of identification. Our results provide a useful step toward a better understanding of human visual perception in context of the known cues.


Study protocol of Phase 2 open-label multicenter randomized controlled trial for granulocyte-colony stimulating factor (GCSF) in post-Kasai Type 3 biliary atresia.
Animal studies support RCT findings of improved liver function and short-term benefits using repurposed Granulocyte Colonic Stimulating Factor GCSF in adults with decompensated cirrhosis. We describe the protocol for phase 2 RCT of sequential Kasai-GCSF under an FDA-approved IND to test that GCSF improves early bile flow and post-Kasai biliary atresia BA clinical outcome. Immediate post-Kasai neonates, age 15-180 days, with biopsy-confirmed type 3 BA, without access to early liver transplantation, will be randomized 1:1 to standard of care SOC + GCSF at 10 ug/kg in 3 daily doses within 4 days of Kasai vs SOC + NO-GCSF (ClinicalTrials.gov NCT0437391). They will be recruited from children's hospitals in Vietnam, Pakistan and one US center. The primary objective is to demonstrate that GCSF decreases the proportion of subjects with a 3-month post-Kasai serum Total Bilirubin ≥ 34 umol/L by 20%, (for a = 0.05, b = 0.80, i.e., calculated sample size of 218 subjects). The secondary objectives are to demonstrate that the frequency of post-Kasai cholangitis at 6-month and 24-month transplant-free survival are improved. The benefits are that GCSF is an affordable BA adjunct therapy, especially in developing countries, to improve biliary complications, enhance quality of liver and survival while diminishing costly liver transplantation.Clinical trial registration: A phase 1 for GCSF dose and safety determination under ClinicalTrials.gov identifier NCT03395028 was completed in 2019. The current Phase 2 trial was registered under NCT04373941.


The lumbosacral angle is a significant predictor for using a semi-rigid ureteroscopic approach in middle ureteral stones.
Ureteroscopy for middle ureteral stones is often difficult from an anatomical view. This study aimed to evaluate the pelvic anatomy in three dimensions and investigate the relationship between the pelvic anatomy and potential semi-rigid ureteroscopic approach for treating middle ureteral stones. From a total of 967 patients who underwent ureteroscopy from December 2017 to January 2021, 124 patients who had middle ureteral stones were included in this retrospective cohort study. The pelvic transverse diameter, pelvic vertical diameter, pelvic depth, and lumbosacral angle were measured through preoperative non-contrast computed tomography to define the shape of the pelvic cavity. The relationship between the reachability of the middle ureteral stone using a semi-rigid ureteroscope and the aforementioned anatomical factors, as well as treatment outcomes, was examined retrospectively. The lumbosacral angle and female sex were significant predictors of the possibility of a semi-rigid ureteroscopic approach to middle ureteral stones [odds ratio =1.08; 95% confidence interval (CI): 1.03-1.14; P=0.003, and odds ratio =3.23; 95% CI: 1.12-9.32; P=0.03, respectively]. The cutoff value of the lumbosacral angle was 149.9°, with a sensitivity of 55.1% and a specificity of 72.7%. The time to reach the stone was longer in the lumbosacral angle <150° group than in the lumbosacral angle ≥150° group (P=0.049). In this study, gradual lumbosacral angle and female sex are positive predictors of the reachability of the middle ureteral stone with a semi-rigid ureteroscope.


Long-term risk of cancer in membranous nephropathy patients.
There is a well-known association between membranous nephropathy (MN) and cancer, and patients with MN usually are examined for cancer at the time of diagnosis. The long-term risk of cancer after MN is not well studied. Cohort study with record linkage between the Norwegian Kidney Biopsy Registry and Norwegian Cancer Registry. 161 patients with MN from 1988 to 2003. Patients with MN compared with the age- and sex-adjusted general Norwegian population. Cancer diagnosis reported through 2003. Mean duration of follow-up was 6.2 years (range, 0.1 to 15 years). 33 patients developed cancer; including 24 patients with cancer after the diagnosis of MN. Median time from diagnosis of MN to diagnosis of cancer was 60 months (range, 0 to 157 months). Mean annual incidence ratio of cancer was 2.4/100 person-years (2.1/100 person-years in the 0- to 5-year period and 2.8/100 person-years for the 5 to 15 years after kidney biopsy). During the 0 to 15 years after the diagnosis of MN, the expected number of cancers was 10.7, resulting in a standardized incidence ratio of cancer of 2.25 (95% confidence interval, 1.44 to 3.35). In the 5 to 15 years after diagnosis, standardized incidence ratio was 2.30 (95% confidence interval, 1.19 to 4.02). Patients with MN who developed cancer were older (65 versus 52 years; P < 0.001). Patients with cancer and MN had a greater mortality rate than patients without cancer (67% versus 26%; P < 0.001). Follow-up treatment after MN with cytotoxic and immunosuppressive medications is not known. An increased risk of developing cancer is observed after the diagnosis of MN, which persists for many years.


Juvenile Drug Treatment Court.
Juvenile drug treatment courts (JDTCs) were established in the 1990s to reduce the cycle of crime, drug use, and delinquency among youthful offenders. The principles and guidelines underlying JDTCs, roles of multidisciplinary team members, and procedures common to JDTCs are described. Youth served by JDTCs are frequently male, identify as racial or ethnic minorities, come from impoverished backgrounds, and experience significant psychiatric comorbidity. This article reviews the small number of clinical trials that have examined adjunctive treatments using family-based and individual behavioral treatment approaches designed to improve the overall efficacy of JDTCs. Considerations for future research on JDTCs are described.


Reliability of Diagnosis and Clinical Efficacy of Cranial Osteopathy: A Systematic Review.
In 2010, the World Health Organization released benchmarks for training in osteopathy in which they considered cranial osteopathy as an important osteopathic skill. However, the evidence supporting the reliability of diagnosis and the efficacy of treatment in this field appears scientifically weak and inconsistent. To identify and critically evaluate the scientific literature dealing with the reliability of diagnosis and the clinical efficacy of techniques and therapeutic strategies used in cranial osteopathy. Relevant keywords were used to search the electronic databases MEDLINE, PEDro, OSTMED.DR, Cochrane Library, and in Google Scholar, Journal of American Osteopathy Association and International Journal of Osteopathic Medicine websites. Searches were conducted up to end June 2016 with no date restriction as to when the studies were completed. As a complementary approach we explored the bibliography of included articles and consulted available previous reviews dealing with this topic. Regarding diagnostic processes in cranial osteopathy, we analyzed studies that compared the results obtained by at least two examiners or by the same examiner on at least two occasions. For efficacy studies, only randomized-controlled-trials or crossover-studies were eligible. We excluded articles that were not in English or French, and for which the full-text version was not openly available. We also excluded studies with unsuitable study design, in which there was no clear indication of the use of techniques or therapeutic strategies concerning the cranial field, looked at combined treatments, used a non-human examiner and subjects or used healthy subjects for efficacy studies. There was no restriction regarding the type of disease. In our electronic search we found 1280 references concerning reliability of diagnosis studies plus four references via our complementary strategy. Based on the title 18 articles were selected for analysis. Nine were retained after applying our exclusion criteria. Regarding efficacy, we extracted 556 references from the databases plus 14 references through our complementary strategy. Based on the title 46 articles were selected. Thirty two articles were not retained on the grounds of our exclusion criteria. Risk of bias in reliability studies was assessed using a modified version of the quality appraisal tool for studies of diagnostic reliability. The methodological quality of the efficacy studies was assessed using the Cochrane risk of bias tool. Two screeners conducted these analyses. For reliability studies, our analysis leads us to conclude that the diagnostic procedures used in cranial osteopathy are unreliable in many ways. For efficacy studies, the Cochrane risk of bias tool we used shows that 2 studies had a high risk of bias, 9 were rated as having major doubt regarding risk of bias and 3 had a low risk of bias. In the 3 studies with a low risk of bias alternative interpretations of the results, such as a non-specific effect of treatment, were not considered. Our results demonstrate, consistently with those of previous reviews, that methodologically strong evidence on the reliability of diagnostic procedures and the efficacy of techniques and therapeutic strategies in cranial osteopathy is almost non-existent.


Impact of sunlight exposure on the residual efficacy of biolarvicides Bacillus thuringiensis israelensis and Bacillus sphaericus against the main malaria vector, Anopheles gambiae.
Biotic and abiotic factors have been reported to affect the larvicidal efficacy of Bacillus thuringiensis israelensis (Bti) and Bacillus sphaericus (Bs), although the extent to which they are affected has been poorly documented. This paper studies the effect of sunlight exposure on the efficacy of a new larvicide formulation based on both Bti and Bs, herein after referred to as BTBSWAX, applied against two different larval stages. The emergence of inhibition exhibited by BTBSWAX at three different dosages (1 g/m2, 1.5 g/m2, and 2 g/m2) was monitored under semi-field conditions using a total of 32 containers comprising 16 that were covered and 16 that were uncovered. Two experiments were conducted using first- and second-instar larvae of Anopheles gambiae, respectively. BTBSWAX at 2 g/m2 in covered containers exhibited high emergence inhibition (> 80%) when larvae were exposed from 1st instar on day-6 post-treatment, whereas the emergence inhibition was only 28% in uncovered containers. For larvae exposed from 1st instar on day-12 post-treatment, the emergence inhibition was moderate (70%) in covered containers but was low (< 20%) in uncovered containers. For larvae exposed from 2nd instar on day-10 post-treatment, the emergence inhibition was moderate (31%) in covered containers but was very low (< 10%) in uncovered containers. Moreover, the residual efficacy of BTBSWAX was markedly affected by environmental stresses, including sunlight exposure (Hazard ratio (HR) = 0.12, p < 0.001 and HR = 0.63, p = 0.033 for BTBSWAX at 2 g/m2 against 1st and 2nd instar larvae, respectively). These findings emphasize the impact of environmental variables (e.g., sunlight exposure) on the residual efficacy of Bti and Bs biolarvicides in the field. They hence highlight the need to take these factors into account for larvicide formulation development processes. Moreover, studies of the ecology of Anopheles larvae in targeted areas are also crucial for the integration of larval control strategies into malaria transmission plans devised by national malaria control programmes of endemic countries.


New bis[MoO2] and [MoO(O2)] compounds: An artificial enzyme with peroxidase activity against o-phenylenediamine and dopamine.
In this study, two binuclear dioxido- and oxidoperoxido molybdenum (VI) complexes, [{MoVIO2}2(L)(H2O)2] 1 and [{MoVIO(O2)}2(L)(H2O)2] 2, were synthesized. Complex 1 was obtained through a 1:2 reaction of ligand I with MoO2(acac)2, while complex 2 was synthesized in situ by reacting MoO3 with H2O2 in a 1:2 ratio. The structures and characteristics of the complexes were examined employing several techniques such as elemental (CHN) analysis, spectroscopy (FT-IR, UV-Vis, 1H, and 13CNMR), and thermal study (TGA). SC-XRD analysis of complex 1a revealed that the molybdenum central atom adopts an octahedral geometry and is bonded to phenolic oxygen, enolate oxygen, and azomethine nitrogen atoms. Powder X-ray diffraction was used to determine the purity of the bulk material, and the results were compared to single crystal data. Computational calculations were performed using density functional theory (DFT) at the B3LYP/6-31G(d, p) level of theory for the ligand and the LANL2DZ level of theory for the complexes, yielding geometry optimized structures that were then employed in frequency and NMR-calculations. These theoretical findings were compared to the experimental results and showed a good correlation. Furthermore, the complexes exhibited peroxidase-like activity in the presence of hydrogen peroxide as evidenced by the oxidation of o-phenylenediamine and dopamine.


BCL-XL exerts a protective role against anemia caused by radiation-induced kidney damage.
Studies of gene-targeted mice identified the roles of the different pro-survival BCL-2 proteins during embryogenesis. However, little is known about the role(s) of these proteins in adults in response to cytotoxic stresses, such as treatment with anti-cancer agents. We investigated the role of BCL-XL in adult mice using a strategy where prior bone marrow transplantation allowed for loss of BCL-XL exclusively in non-hematopoietic tissues to prevent anemia caused by BCL-XL deficiency in erythroid cells. Unexpectedly, the combination of total body γ-irradiation (TBI) and genetic loss of Bcl-x caused secondary anemia resulting from chronic renal failure due to apoptosis of renal tubular epithelium with secondary obstructive nephropathy. These findings identify a critical protective role of BCL-XL in the adult kidney and inform on the use of BCL-XL inhibitors in combination with DNA damage-inducing drugs for cancer therapy. Encouragingly, the combination of DNA damage-inducing anti-cancer therapy plus a BCL-XL inhibitor could be tolerated in mice, at least when applied sequentially.


From guidelines to practice: how reporting templates promote the use of radiology practice guidelines.
Radiology practice guidelines have been developed to help radiologists achieve quality and safety in their clinical practice. One means to promote the use of practice guidelines in radiology is through the wider use of reporting templates, also known as "structured reporting." This article presents specific examples in which radiology reporting templates can promote adherence to guidelines, gather data for quality improvement efforts, and facilitate compliance with performance incentive programs.


Administration of granulocyte colony-stimulating factor to recipients followed by intra-bone marrow-bone marrow transplantation accelerates acceptance of allogeneic bone marrow cells in mice.
We have recently established a novel method for bone marrow transplantation: intra-bone marrow-bone marrow transplantation (IBM-BMT), by which the rapid recovery of donor-derived hematopoiesis can be expected even when reduced radiation doses are used. In this paper, we examine, using mice, whether the combination of pretreatment of recipients with granulocyte-colony-stimulating factor (G-CSF) and IBM-BMT can induce a more rapid recovery of donor-derived hematopoiesis than IBM-BMT alone. We first pretreated recipients with recombinant human (rh) G-CSF (250 microg/kg/day) for 5 consecutive days (days -6 to -2). On day -1, the recipients were irradiated, and IBM-BMT was carried out on day 0. On day 12, we performed colony-forming units of spleen (CFU-S) assays. The combination of G-CSF pretreatment and IBM-BMT augmented the CFU-S counts, the weight of spleens, and the numbers of donor-derived hematopoietic cells. We next analyzed the mechanisms underlying these effects of G-CSF and found that (i) G-CSF induces Th2 polarization, which can prevent graft rejection, and (ii) G-CSF augments natural suppressor activity, which suppresses graft rejection. The combination of G-CSF pretreatment and IBM-BMT can produce the rapid recovery of donor-derived hematopoiesis and suppress graft rejection. This method would lighten the burden on patients in allogeneic BMT.


Life strategies for Aminicenantia in subseafloor oceanic crust.
After decades studying the microbial "deep biosphere" in subseafloor oceanic crust, the growth and life strategies in this anoxic, low energy habitat remain poorly described. Using both single cell genomics and metagenomics, we reveal the life strategies of two distinct lineages of uncultivated Aminicenantia bacteria from the basaltic subseafloor oceanic crust of the eastern flank of the Juan de Fuca Ridge. Both lineages appear adapted to scavenge organic carbon, as each have genetic potential to catabolize amino acids and fatty acids, aligning with previous Aminicenantia reports. Given the organic carbon limitation in this habitat, seawater recharge and necromass may be important carbon sources for heterotrophic microorganisms inhabiting the ocean crust. Both lineages generate ATP via several mechanisms including substrate-level phosphorylation, anaerobic respiration, and electron bifurcation driving an Rnf ion translocation membrane complex. Genomic comparisons suggest these Aminicenantia transfer electrons extracellularly, perhaps to iron or sulfur oxides consistent with mineralogy of this site. One lineage, called JdFR-78, has small genomes that are basal to the Aminicenantia class and potentially use "primordial" siroheme biosynthetic intermediates for heme synthesis, suggesting this lineage retain characteristics of early evolved life. Lineage JdFR-78 contains CRISPR-Cas defenses to evade viruses, while other lineages contain prophage that may help prevent super-infection or no detectable viral defenses. Overall, genomic evidence points to Aminicenantia being well adapted to oceanic crust environments by taking advantage of simple organic molecules and extracellular electron transport.


Associations of non-traditional cardiovascular risk factors and body mass index with metabolic syndrome in the Chinese elderly population.
Metabolic syndrome (MetS), a clustering of traditional cardiovascular risk factors (CVRF), is currently one of the major global public health burdens. However, associations between MetS and non-traditional CVRF represented by uric acid (UA), homocysteine (HCY) and hypersensitive C-reactive protein (HsCRP) have not been well explored in the elderly population, especially when considering body mass index (BMI). Participants from the Shanghai Elderly Cardiovascular Health (SHECH) study cohort in 2017 were analyzed. MetS was defined using the modified American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Logistic regression models were used to assess associations of non-traditional CVRF, BMI with MetS. Of the 4360 participants analyzed, 2378 (54.5%) had MetS, the mean (SD) UA was 331 (86) µmol/L, and the median (IQR) HCY and HsCRP were 15 (13-18) µmol/L and 1.0 (0.5-2.1) mg/L, respectively. Participants with higher non-traditional CVRF tended to have a higher significant risk of MetS (P < 0.001), which did not changed substantially in most population subgroups (P-interaction > 0.05). BMI mediated 43.89% (95%CI: 30.38-57.40%), 37.34% (95% CI: 13.86-60.83%) and 30.99% (95%CI: 13.16-48.83%) of associations of hyperuricemia (HUA), hyperhomocysteinemia (HHCY) and high HsCRP (HHsCRP) with MetS, respectively. Abnormal non-traditional CVRF combined with overweight/obesity greatly increased MetS risk (adjusted OR(95%CI): HUA + Overweight: 5.860(4.059-8.461); 6.148(3.707-10.194); HHCY + Overweight: 3.989(3.107-5.121); HHCY + Obese: 5.746(4.064-8.123); HHsCRP + Overweight: 4.026(2.906-5.580); HHsCRP + Obese: 7.717(4.508-13.210)). In the Chinese elderly population, HUA, HHCY, and HHsCRP were all significantly and independently associated with MetS, supporting the potential of focusing on non-traditional CVRF interventions for preventing and controlling MetS. BMI played moderate mediating roles in associations between non-traditional CVRF and MetS, and abnormal non-traditional CVRF combined with overweight/obesity had significant synergistic effects on MetS risk, highlighting the importance of better weight management in the elderly population.


Status of genes encoding the mitochondrial S1 ribosomal protein in closely-related legumes.
The rps1 gene, which encodes ribosomal protein S1 of the mitochondrial ribosome in flowering plants, is located in the mitochondrion of some but not all species, and this is assumed to reflect multiple gene transfers to the nucleus. We investigated its status in legumes and found that in alfalfa, sweet clover and fenugreek, the mitochondrial-located rps1 is a pseudogene, in contrast to intact, transcribed and edited rps1 genes in the mitochondria of rest harrow, pea, soybean and bean. Among these lineages, the genomic environment upstream of rps1 differs, and this contrasts with a stable downstream linkage with the first two exons of the trans-split nad5 gene. Consequently, the rps1 transcript profiles differ for each of these closely-related species, and typically do not include monocistronic rps1 or nad5 mRNAs. In alfalfa, sweet clover and fenugreek, the functional rps1 gene is located in the nucleus and it is still flanked by residual non-coding mitochondrial sequences. Notably, the upstream ones provide part of the 5' UTR as well as the 3' splice site of an intron preceding rps1. This exploitation of non-coding mitochondrial sequences in nuclear gene activation adds to a growing list of mechanisms by which successful transfer of mitochondrial genes is achieved.


[The integral assessment of subject symptoms for detecting chronic visual, motor and nonspecific fatigue in workers].
The authors present methods of integral evaluation of symptoms for diagnosis of chronic visual, locomotor and nonspecific fatigue in workers. Questionnaires and algorithms to treat them are incorporated into the methods that are to be used in hygienic regulation of work, particularly, to reveal comparative significance of work factors--visual efforts, physical hardiness and nerve strain.


Epigenetic Dysregulation of Dopaminergic System by Maternal Cafeteria Diet During Early Postnatal Development.
Dopamine is a neurotransmitter crucial for motor, motivational, and reward-related functions. Our aim was to determine the effect of a palatable maternal diet on the transcriptional regulation of dopaminergic-related genes during perinatal development of rat offspring. For that, female offspring from dams fed with a control (CON) or a cafeteria (CAF) diet were sacrificed on embryonic day 21 (E21) and postnatal day 10 (PND10). Using micropunch techniques, ventral tegmental area (VTA) and nucleus accumbens (NAc) were isolated from brain's offspring. Bioinformatic analysis of the promoter regions, mRNA quantification and methylation studies were done. The increase in tyroxine hidroxylase (TH), dopamine receptor (DRD) 1 and ghrelin receptor (GHSR) expression in VTA and NAc from E21 to PND10 was correlated with changes in DNA methylation of their promoter regions. Maternal diet did not affect the expressionpatternsin E21. At PND10, maternal CAF diet decreased the transcription of TH, GHSR, DRD2 and dopamine transporter (DAT) in VTA. Interestingly, the changes in TH, DRD2 and DAT expression were related to the methylation status of their promoters. In NAc, maternal CAF diet reduced DRD1, DRD2 and DAT expression in the offspring at PND10, although alternations in the methylation patterns were only detected in DAT promoter. These results show the importance of maternal nutrition and provide novel insights into the mechanisms through which maternal junk-food feeding can affect reward system during development and early postnatal life. Particularly important is the expression decline of DRD2 given its physiological implication in obesity and addiction.


Obtaining Information from Family Caregivers Is Important to Detect Behavioral and Psychological Symptoms and Caregiver Burden in Subjects with Mild Cognitive Impairment.
The objectives of this study are to clarify the differences between the difficulties in daily life experienced by patients with both mild cognitive impairment (MCI) and chronic disease and those experienced by healthy elderly individuals. We assessed (a) cognitive function; (b) gait ability; (c) behavioral and psychological symptoms (observed at home); (d) activities of daily living (observed at home); (e) family caregiver burden, and (f) intention to continue family caregiving of 255 cognitively normal and 103 MCI subjects attending adult day care services covered by long-term care insurance, and compared the two groups. Subjects with MCI display more behavioral and psychological symptoms than cognitively normal subjects, posing a heavy caregiver burden (p < 0.01). Behavioral and psychological symptoms most commonly observed in subjects with MCI are apathy, hallucinations, delusions, agitation, and aberrant motor behavior. Information regarding the behavioral and psychological symptoms displayed at home by patients with MCI can only be obtained from family caregivers living with the patients. To provide early-stage support for elderly patients with MCI, adult day care workers should collect information from family caregivers regarding behavioral and psychological symptoms observed at home.


Effects of cold shock treatment on amphibian oocytes: alteration of heterogenous nuclear RNP morphology.
In cold-stressed oocytes of Pleurodeles waltl, lampbrush chromosome lateral loops exhibited important structural modifications which were visualized under light microscopy. Electron microscopy study revealed that the RNP particles associated with growing transcripts in the matrix of these loops were 15 nm at 8 degrees C compared to 30 nm at normal temperature (20 degrees C); hnRNP isolated from cold-stressed oocytes sedimented at 15 S in sucrose, while those from control oocytes sedimented at 30 S, as expected. However, under both normal and cold stress conditions, hnRNP possessed a buoyant density of 1.38 g/cm3 in CsCl, indicating that their typical RNA/protein ratio was maintained at 8 degrees C. Our results demonstrate that cold stress affects the structure of hnRNP in amphibian oocytes.


Effects and Mechanisms of Traditional Chinese Herbal Medicine in the Treatment of Ischemic Cardiomyopathy.
The incidence of ischemic cardiomyopathy (ICM) is increasing yearly, which seriously endangers human health. There is rarely any remarkable progress in the treatment of ICM from the available drugs. Recent research shows that natural herbal medicine may have beneficial effects in the prevention and treatment of cardiovascular diseases. The effective extracts of the herbs may improve myocardial ischemia through various actions, such as hemodynamic, hemorheological, and vascular actions, and on various cell biology aspects, such as intracellular calcium balance, mitochondria function, cell apoptosis, and scavenging free radicals. Here, we review the animal research progress and potential mechanisms in the treatment of ICM using extracts of well-known traditional Chinese herbal medicines.


HLA in multiple sclerosis. Relationship to measles antibody, mitogen responsiveness and clinical course.
In our study of multiple sclerosis (MS) patients we have found significant increases in the A3, B7, and DW2 antigens. We have also studied immune responses in these same patients. There was elevation of measles antibodies in MS patients positive for A3, B7, and B18 as compared to MS patients without those antigens. The first study of mitogen responsiveness (31 patients) showed a decreased response in A3, and B7 positive patients. Study of a second and a larger group (62 patients), at a different time, failed to confirm this deficiency. We propose that there is a genetically linked (HLA) T cell deficiency in some MS patients and that this deficiency results in high humoral responses to measles antigens and an evanescent (or cyclical) reduced T cell response to mitogen.


Photo-induced reduction of vanadium in vanadium-containing iron/manganese oxide agglomerates by oxalic acid.
The stockpiling of vanadium-containing tailings allows vanadium to migrate into the surrounding area, resulting in toxic metal contamination. By using the vanadium-bearing iron/manganese (Fe/Mn) oxide agglomerates as the simulated tailings, the feasibility of photo-induced reduction of vanadium by oxalic acid was investigated. Batch effects of the available light and the reducing agents on agglomerates were investigated. Results showed that oxalic acid (5 mmol L-1) can convert V(V) to V(IV) and convert Fe(III) released from the Fe/Mn oxide agglomerates to Fe(II) under both light and dark conditions. After 45 d of reaction in the dark, oxalic acid converted 33.54% Fe(III) and 100% V(V) in the leachate into Fe(II) and V(IV). The Fenton reaction occurred by light irradiation significantly increased the redox potential in the solution, and also caused V(IV) to be oxidized. Overall, oxalic acid can rapidly reduce V(V) to V(IV), but sunlight may have an inhibitory effect on the reduction reaction. Present study can deepen the understanding of the mechanism for valence transformation of elements in minerals by sunlight, and can help in implementing tailings treatment and environmental remediation by using oxalic acid and avoiding light.


Change of gait after unilateral vestibular neuritis: a prospective longitudinal observation study.
Although symptoms of unilateral vestibular neuritis (uVN) resolve spontaneously within several weeks, recovery of gait function has unclearness in gait parameter changes and mediolateral stability improvements. In addition, prospective longitudinal studies on gait parameters after uVN are lacking. This study was conducted to reveal longitudinal change of gait function after acute uVN and to help the precise rehabilitation planning. Twenty three participants with uVN and 20 controls were included. 3D gait analyses were conducted three times after uVN onset at monthly intervals. From the gait analysis data, spatio-temporal parameters, inclination angle (IA) representing the relationship between center of mass (CoM) and center of pressure (CoP) in the frontal plane, and IA variability were obtained. Time effects on gait metrics were tested. Walking speed of participants with uVN improved significantly between the 1st and 3rd tests, but they were not significantly different to that of control, even in the 1st test. The step width of participants with uVN was significantly larger than that of control in the 1st test and improved significantly in the 2nd test. Variability of IA in affected side was significantly larger than that in controls in the 1st test and improved significantly in the 3rd test compared to the 1st test. Improvement of overall gait function and mediolateral stability during gait continued after acute stage of uVN (two months from onset in this study). Rehabilitation intervention should be continued after the acute stage of uVN to enhance appropriate adaptation in gait.


Critical review and recommendations for nesiritide use in the emergency department.
Heart failure is a disease of epidemic proportions. Almost five million Americans suffer from heart failure and over 400,000 patients are newly diagnosed with heart failure each year. Indeed, heart failure is now the only cardiovascular disease that is increasing in incidence and prevalence. Costs related to heart failure are $18.8 billion per year and are steadily increasing. Although the outpatient management of these patients has seen substantial improvement in the last two decades, emergency department (ED) treatment of acute decompensated heart failure has remained largely unchanged since the late 1970s. Current ED therapy consists of diuretics, intravenous vasodilatators, and inotropes. Recently, the outcomes of several high-profile clinical trials evaluating intravenous nesiritide (human B-type natriuretic peptide) have suggested a benefit in select hospitalized patients. Such a therapy has potential to provide a therapeutic addition or alternative for emergency heart failure management. We discuss these trials' results, suggest their relationship to the ED population, and provide recommendations for appropriate ED use.


Establishing and Evaluating an ASCO Learning Cohort: a Longitudinal Project Assessing the Learning Needs and Behaviors of Oncology Professionals.
In 2013, the American Society of Clinical Oncology (ASCO)'s Continuing Education Committee recommended establishing an interprofessional, longitudinal cohort pilot project. The main goals of the cohort were to gain feedback from oncology providers on how they use resources to address their learning needs and gain insights into the utility of different ASCO educational activities. The ASCO Learning Cohort Pilot Project included 49 ASCO members that were representative of the overall Society membership demographics and ran from November 2015 through August 2016. Participants documented monthly learning needs and completed monthly feedback activities focused on specific ASCO educational resources. The Learning Cohort Pilot Project proved a viable and innovative cohort model for analyzing the learning process for oncology healthcare professionals. The development, operations, and compliance required unique infrastructure to accomplish this project. Relationships between participant demographic variables and learning preferences are reported elsewhere. The ASCO Learning Cohort Project is a unique educational project that demonstrated feasibility and has met its goals. This paper outlines the processes of establishing a learning cohort, including participant selection, project design, and participant feedback. We evaluate the project model as a means to better understand the learning needs and behaviors of oncology healthcare professionals.


Scanning Electron Microscope Corroboration of Ameloglyphics - A New Tool in Forensic Odontology.
Human teeth resist decomposition to the maximum and has immense potential to serve as hard-tissue counterpart to dermatoglyphics in forensic odontology. Ameloglyphics is the science of recording and analyzing the tooth print. To assess the scope of viability, reproducibility, and identification of enamel prints (akin to fingerprints) and their patterns as a tool for identification. To establish that expression of enamel prints is a direct result of the enamel rod configuration on the surface of the crown as detected by scanning electron microscope (SEM). The teeth samples (n = 10) were first analyzed through (SEM) and the image of the arrangement of rods on the surface was captured. Enamel prints were registered in a standard procedure by virtue of ink transfer on a cellophane tape from etched tooth enamel surface of the same samples. These prints and SEM images were subjected to Rapid Sizer® image editing software to obtain a pattern (sketched outline image software). Patterns were identified manually. Reproducibility, specificity, and feasibility of the above procedure were determined. There appeared to be a high rate of reproducibility (98%-100%) and specificity (100%). The paraphernalia required as well as the technique entrenched were feasible. Furthermore, the SEM analysis established the viability and reliability. Ameloglyphics is a sensitive and reproducible scientific tool that can be utilized for the management, examination, and evaluation of dental evidence for identification at crime scene and disaster sites. Its importance vis-a-vis fingerprints cannot be understated, especially in view of the seeming indestructibility of the enamel.


At the origin of "Endocrinology and Art": Woman's Head (third century BCE).
In 1911, the Danish physician Hans Christian Gram (1853-1938) sustained to have found signs of hyperthyroidism in a marble head of a Roman woman that he observed in the Ny Carlsberg Glyptotek in Copenhagen. It could be one of the first examples of a clinical diagnosis of an endocrine disease in an ancient statue.


Effects of environmental exposure to polychlorinated biphenyls and dioxins on cognitive abilities in Dutch children at 42 months of age.
To study possible adverse effects of environmental exposure to polychlorinated biphenyls (PCB) and dioxins on cognitive functioning in young children. In a follow-up of the Dutch PCB/Dioxin study, cognitive abilities were assessed with the Kaufman Assessment Battery for Children in 42-month-old children (n = 395). In a subgroup (n = 193) verbal comprehension was assessed with the Reynell Language Developmental Scales. Prenatal PCB exposure was estimated from the sum of PCBs 118, 138, 153, and 180 (SigmaPCB) in maternal plasma. Lactational exposure was assessed from breast milk PCB and dioxin concentrations, multiplied by the number of weeks of breast-feeding. Current PCB body burden was estimated from SigmaPCB in 42-month-old plasma samples. After adjustment was done for covariables, maternal SigmaPCB was associated with lower scores on the overall cognitive and sequential and simultaneous processing scales of the Kaufman Assessment Battery for Children (all P <.05). The highest exposed group (SigmaPCB >/= 3 microg/L) scored 4 points lower on all 3 scales of the K-ABC when compared with the lowest exposed group (SigmaPCB < 1.5 microg/L). Both lactational exposure and current exposure to PCBs and dioxins were not related to 42-month cognitive performance. In utero exposure to "background" PCB concentrations is associated with poorer cognitive functioning in preschool children. Children of mothers at the upper end of exposure are especially at risk. Therefore maternal PCB body burden should be reduced, and breast-feeding should not be discouraged.


A technique of airway management in children with obstructed airway due to tumor.
Airway management of patients with tracheobronchial compression due to mediastinal masses poses a difficult problem. A new technique of direct vision endotracheal intubation is described, and other adjunctive measures are reviewed.


Activation of the extrinsic coagulation pathway in patients with severe sepsis and septic shock.
To obtain systematic information on the extrinsic coagulation pathway, as well as to investigate the time course of the coagulation abnormalities in sepsis. Prospective observational study. General intensive care unit. Nineteen patients with the diagnosis of severe sepsis or septic shock and nine control patients. None. Tissue factor antigen concentration (tissue factor antigen), prothrombin fragment F1+2, thrombin antithrombin III complex, fibrinopeptide A, D-dimer, and antithrombin III concentrations were measured on the day of diagnosis of severe sepsis and septic shock, and on days 1, 2, 3, and 4 after diagnosis. The concentrations of tissue factor antigen, prothrombin fragment F1+2, fibrinopeptide A, and D-dimer were significantly increased in patients with severe sepsis and septic shock compared with control subjects. However, the concentrations of thrombin antithrombin III complex showed no statistical differences between the septic patients and the control subjects. Significantly, low antithrombin III concentrations were observed in the septic patient groups compared with control subjects. With the exception of D-dimer, the concentrations of the hemostatic markers were similar between severe sepsis and septic shock patients. Significant correlations were noted between tissue factor antigen and the disseminated intravascular coagulation score (r2=.236, p< .0001) and the number of dysfunctioning organs (r2=.229, p=.035). We systematically elucidated coagulation disorders in newly defined sepsis. The extrinsic coagulation pathway is activated in patients with severe sepsis and septic shock. In these patients, enhanced thrombin generation and activation, and fibrin formation were demonstrated when compared with the control subjects. Furthermore, the thrombin generated appears not to be fully neutralized by antithrombin III.


2-Bromo- and 16-bromo-estrogens and related compounds: potential inhibitors for both estradiol 2- and 16 alpha-hydroxylases in rat liver microsomes.
Kinetic studies of inhibition of estradiol 2- and 16 alpha-hydroxylase activities in male rat liver microsomes with 2-bromoestrogens, 4-bromo-estrone (4-BrE1), 16 alpha- and 16 beta-bromoestrones and 16 beta-acetylthioestrone (16-AcSE1) were carried out. 2-Bromoestrogens and 4-BrE1 nonspecifically blocked the two enzyme activities in a competitive manner, and 2-bromo-estradiol (2-BrE2) was the most potent inhibitor for the two hydroxylases among the 2- and 4-bromo steroids. Kinetic data, the apparent Ki's for the inhibitors and the apparent Km's for the substrate E2 in the assay, demonstrate that the A-ring bromo steroids are potent inhibitors for the two enzymes (Ki/Km ranging from 0.28 to 0.48 for the 2-hydroxylation and ranging from 0.26 to 0.49 for the 16 alpha-hydroxylation). In contrast, 16-bromoestrones and 16-AcSE1 non-competitively inhibited the 2-hydroxylation (Ki = ca. 70 microM) while the other was competitively blocked by them (Ki/Km ranging from 0.24 to 0.30). These 16-substituted steroids were very potent inhibitors for the 16 alpha-hydroxylase rather than the 2-hydroxylase and preferentially blocked the former.


A comprehensive platform for ex vivo T-cell expansion based on biodegradable polymeric artificial antigen-presenting cells.
Efficient T-cell stimulation and proliferation in response to specific antigens is a goal of immunotherapy against infectious disease and cancer. Manipulation of this response can be accomplished by adoptive immunotherapy involving the infusion of antigen-specific T-cell populations expanded ex vivo with antigen presenting cells. We mimicked physiological antigen presentation on a biodegradable microparticle constructed from poly(lactide-co-glycolide) (PLGA), a polymer system whose safety has been established for use in humans. These particles present a high density of adaptor elements for attaching both recognition ligands and co-stimulatory ligands to a biodegradable core encapsulating the cytokine interleukin-2 (IL-2). We demonstrate the utility of this system in efficient polyclonal and antigen-specific T-cell stimulation and expansion, showing that sustained release of IL-2 in the vicinity of T-cell contacts dramatically improves the stimulatory capacity of these acellular systems, as compared to the effect of exogenous addition of cytokine. This results in a 45-fold enhancement in T-cell expansion. In addition, this mode of antigen presentation skews the expansion toward the CD8(+) T-cell phenotype. This comprehensive acellular platform, capable of delivering recognition, co-stimulatory, and cytokine signals, represents a promising new technology for artificial antigen presentation.


[About the importance of chemical flocculation of wastewater in regard to hygienical aspects (microbiological and virological examinations in a wastewater treatment plant) (author's transl)].
In a small wastewater treatment plant corresponding samples from the intake and outtake of the chemical flocculation were chemically, microbiologically and virologically investigated and compared. It was found that both, the plate count and the number of coliforms, decreased about 90% to 95%. The phosphate content went down about 88%. The BOD5 reduction was ca. 80%, the COD reduction ca. 50%. Poliomyelitisviruses were found regularly in the intake but never in the outtake. Specially in regard to the high plate count- and virusreduction the chemical flocculation seems to be remarkable from the hygienical point of view not only for limnic but also for coastal waters.


Fecal Incontinence and Pelvic Floor Dysfunction in Women: A Review.
Pelvic floor dysfunction and fecal incontinence is a common and debilitating condition in women, particularly as women age, and often goes under-reported to health care providers. It is important for providers to ask patients about possible symptoms. An algorithm for evaluation and treatment is presented. Current and future therapies are described and discussed.


Ergot drugs suppress plasma levels of prolactin (PRL) but not growth hormone (GH), luteinizing hormone (LH) or corticosterone (CORT) in parturient mice.
Plasma levels of prolactin (PRL), growth hormone (GH), luteinizing hormone (LH), and corticosterone (CORT) were measured in parturient Rockland-Swiss (R-S) albino mice following the daily administration for 10 days of 0.5 mg ergocornine (ERGO), 0.5 mg bromocriptine (BROMO), or sesame oil (OIL). The dams were provided with replete foster young on a daily basis so as to prevent the decline in suckling activity that normally occurs in undernourished pups of ergot-treated dams. Circulating PRL levels were significantly reduced by both ergot drugs but plasma levels of the other hormones measured were not altered. Thus, ergot drugs have relatively specific effects on PRL even in parturient animals receiving sustained high levels of suckling stimulation.


Retracted: Study on the Influence of Urban Built Environment Factors on the Social Behavior of ASD Children.
[This retracts the article DOI: 10.1155/2022/8963416.].


A comprehensive study on bisphenol A degradation by newly isolated strains Acinetobacter sp. K1MN and Pseudomonas sp. BG12.
Bisphenol A (BPA) is an endocrine disrupting chemical. Its extensive use has led to the wide occurrence of BPA in various environmental ecosystems, at levels that may cause negative effects to the ecosystem and public health. Although there are many bacteria able to BPA utilization, only a few of them have a strong capacity for its biodegradation. Therefore, it is important to search for new bacteria strains, investigate their BPA biodegradation ability and potential effect of pH and other organic compounds on the process. These tasks have become the object of the present study. The results of our research show that for the newly isolated strains Acinetobacter sp. K1MN and Pseudomonas sp. BG12 after 15 days, with an initial BPA concentration of 100 mg L- 1, the highest BPA removal was achieved at pH 8, while sodium glutamate as a biostimulant best accelerated BPA degradation. Kinetic data for BPA biodegradation by both strains best fitted the Monod model. The specific degradation rate and the half saturation constant were estimated respectively as 8.75 mg L- 1 day- 1 and 111.27 mg L- 1 for Acinetobacter sp. K1MN, and 8.6 mg L- 1 day- 1 and 135.79 mg L- 1 for Pseudomonas sp. BG12. The half-maximal effective concentration (EC50) of BPA for Acinetobacter sp. K1MN was 120 mg L- 1 and for Pseudomonas sp. BG12 it was 123 mg L- 1. The toxicity bioassay (Microtox test) showed that elimination of BPA by both strains is accompanied by reduction of its toxic effect. The ability of tested strains to degrade BPA combined with their high resistance to this xenobiotic indicates that Acinetobacter sp. K1MN and Pseudomonas sp. BG12 are potential tools for BPA removal during wastewater treatment plant.


Antibiotics from Basidiomycetes. XVI. Antimicrobial and cytotoxic polyines from Mycena viridimarginata Karst.
Two new biologically active polyines were isolated from cultures of the fungus Mycena viridimarginata. Their structures were elucidated by spectroscopic and chemical methods as 10-hydroxy-undeca-2,4,6,8-tetraynamide (1) and 3,4,13-trihydroxy-tetradeca-5,7,9,11-tetraynoic acid-gamma-lactone (2). The main component (1) is highly antibiotically active and cytotoxic.


IGFBP2 expressing midlobular hepatocytes preferentially contribute to liver homeostasis and regeneration.
Although midlobular hepatocytes in zone 2 are a recently identified cellular source for liver homeostasis and regeneration, these cells have not been exclusively fate mapped. We generated an Igfbp2-CreER knockin strain that specifically labels midlobular hepatocytes. During homeostasis over 1 year, zone 2 hepatocytes increased in abundance from occupying 21%-41% of the lobular area. After either pericentral injury with carbon tetrachloride or periportal injury with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), IGFBP2+ cells replenished lost hepatocytes in zones 3 and 1, respectively. IGFBP2+ cells also preferentially contributed to regeneration after 70% partial hepatectomy, as well as liver growth during pregnancy. Because IGFBP2 labeling increased substantially with fasting, we used single nuclear transcriptomics to explore zonation as a function of nutrition, revealing that the zonal division of labor shifts dramatically with fasting. These studies demonstrate the contribution of IGFBP2-labeled zone 2 hepatocytes to liver homeostasis and regeneration.


Expression of glucocorticoid receptors in nephrotic children depending on total prednisone dose.
To evaluate the expression of glucocorticoid receptors (GCR) in lymphocytes (CD3/ GCR) and monocytes (CD14/GCR) in children with nephrotic syndrome (NS). The patients were divided into two groups: group I: 17 children with the first NS attack, and group II: 17 children with a subsequent NS event. In both groups, examinations were carried out before treatment (A) and after albuminuria disappearance during prednisone treatment (B). The control group (C) consisted of 23 healthy children, never treated with glucocorticosteroids. Flow cytometry was employed twice to determine the number of CD3+ lymphocytes and CD14+ monocytes and the percentage of CD3/GCR+ and CD14/GCR+ cells. In group I, the expression of CD3/GCR before treatment (A) decreased during prednisone therapy (B) (p < 0.01), but CD14/GCR did not change. In group II, before treatment (A), both CD3/GCR and CD14/GCR were markedly lower compared to the controls and group I. In examination B, both CD3/GCR and CD14/GCR had decreased. A low number of GCR might confer a worse response to glucocorticoid therapy. Longitudinal studies should be performed on larger groups of children with their first and subsequent nephrotic syndome attacks.


Changes to the law on consent following Montgomery vs Lanarkshire Health Board.
The Supreme Court's determination on Montgomery (AP) (Appellant) v Lanarkshire Health Board (Respondent) (Scotland) [2015] clarified UK law on consent. It is for the informed patient to determine which intervention, if any, they will undergo. All doctors must meet this standard and may need to reassess their practice to do so.


Obesity and female sexual dysfunctions: A systematic review of prevalence with meta-analysis.
Obesity represents a major global health challenge. Female sexual dysfunctions have a negative impact on quality of life and overall health balance. A higher rate of female sexual dysfunctions in obese women has been suggested. This systematic review summarized the literature on female sexual dysfunction prevalence in obese women. The review was registered (Open Science Framework OSF.IO/7CG95) and a literature search without language restrictions was conducted in PubMed, Embase and Web of Science, from January 1990 to December 2021. Cross-sectional and intervention studies were included, the latter if they provided female sexual dysfunction rate data in obese women prior to the intervention. For inclusion, studies should have used the female sexual function index or its simplified version. Study quality was assessed to evaluate if female sexual function index was properly applied using six items. Rates of female sexual dysfunctions examining for differences between obese vs class III obese and high vs low quality subgroups were summarized. Random effects meta-analysis was performed, calculating 95% confidence intervals (CI) and examining heterogeneity with I2 statistic. Publication bias was evaluated with funnel plot. There were 15 relevant studies (1720 women participants in total with 153 obese and 1567 class III obese women). Of these, 8 (53.3%) studies complied with >4 quality items. Overall prevalence of female sexual dysfunctions was 62% (95% CI 55-68%; I2 85.5%). Among obese women the prevalence was 69% (95% CI 55-80%; I2 73.8%) vs 59% (95% CI 52-66%; I2 87.5%) among those class III obese (subgroup difference p=0.15). Among high quality studies the prevalence was 54% (95% CI 50-60%; I2 46.8%) vs 72% (95% CI 61-81%; I2 88.0%) among low quality studies (subgroup difference p=0.002). There was no funnel asymmetry. We interpreted that the rate of sexual dysfunctions is high in obese and class III obese women. Obesity should be regarded as a risk factor for female sexual dysfunctions.


Symptoms of posttraumatic stress partially mediate the relationship between gender-based violence and alcohol misuse among South African women.
The association of traumatic experiences with problematic alcohol use has been described, but data on possible mediation effects of mental distress are sparse. We examined whether mental ill-health mediated the association between trauma exposure across the lifespan and alcohol use. We analysed cross-sectional data from a sample of rape-exposed and non-rape-exposed women, living in KwaZulu-Natal, with self-reported data on alcohol misuse (AUDIT-C cut-off ≥ 3) and exposure to childhood maltreatment (CM), intimate partner violence (IPV), non-partner sexual violence (NPSV), other traumatic events, and mental ill-health. Logistic regression and multiple mediation models were used to test the mediation effects of symptoms of depression and PTSS on the association between abuse/trauma and alcohol misuse. Of 1615 women, 31% (n = 498) reported alcohol misuse. Exposure to any CM (adjusted odds ratio (aOR): 1.59, 95% confidence interval (CI): 1.27-1.99), as well as to sexual, physical and emotional CM, were independently associated with alcohol misuse. Lifetime exposure to any IPV (aOR:2.01, 95%CI:1.59-2.54), as well as to physical, emotional and economic IPV, NPSV (aOR: 1.75, 95%CI: 1.32-2.33), and other trauma (aOR:2.08, 95%CI:1.62-2.66), was associated with alcohol misuse. Exposure to an increasing number of abuse types, and other traumatic events, was independently associated with alcohol misuse. PTSS partially mediated the associations of CM, IPV, NPSV and other trauma exposures with alcohol misuse (ps ≤ 0.04 for indirect effects), but depression symptoms did not. These findings highlight the need for trauma-informed interventions to address alcohol misuse that are tailored to the needs of women who have experienced violence.


[Vancomycin-resistant Enterococcus in an epidemic situation: screening at admission for patients at risk of carriage].
To evaluate a strategy based on screening and isolation at admission to a department of infectious diseases during an epidemic of vancomycin-resistant Enterococcus (VRE) at the University Hospital of Clermont-Ferrand. Systematic screening for VRE by anal swabs began on November 15, 2004. Patients were isolated on admission if (a) they had been hospitalized more than 24 h in an at-risk department of our hospital or (b) they had received a course of wide-spectrum antimicrobial therapy for longer than 48 h in the three months preceding admission. Patients hospitalized in our department were screened weekly if they were treated with wide-spectrum antibiotics, had a urinary catheter left in place for one week, or were neutropenic. Through May 15, 2005, 12 (3.5%) of 341 swabs were found to be positive for VRE: eight were detected on admission and four during hospitalization. In all, 81 patients were isolated on admission. A case-control study confirmed that the criteria for patient isolation were indeed risk factors for VRE. Isolation was well accepted when it was clearly explained. No new case has been detected since March 2005. An isolation strategy based on known risk factors for VRE with systematic screening on admission appears to be an effective way to control an outbreak of VRE, perhaps in part because it helps to keep the medical staff alert to this problem. Isolation is well tolerated as long as it is explained clearly.


Systematic Review of In Vivo Animal Models of Subarachnoid Hemorrhage: Species, Standard Parameters, and Outcomes.
In preclinical models, modification of experimental parameters associated with techniques of inducing subarachnoid hemorrhage (SAH) can greatly affect outcomes. To analyze how parameter choice affects the relevance and comparability of findings, we systematically reviewed 765 experimental studies of in vivo animal SAH models (2000-2014). During the last decade, we found marked increases in publications using smaller species and models for simulating acute events after SAH. Overall, the fewer types of species and models used did not correlate with an increased standardization in the experimental characteristics and procedures. However, by species, commonly applied, reliable parameters for each experimental SAH technique were identified in mouse, rat, rabbit, and dog models. Our findings can serve as a starting point for discussion toward a more uniform performance of SAH experiments, development of preclinical SAH common data elements, and establishment of standardized protocols for multicenter preclinical trials.


Descriptive study of hospital care on toxicological events in a municipality of São Paulo State, Brazil, 2012.
to describe the epidemiological profile of hospital care on chemical exposure cases and accidents with venomous animals performed in a municipal hospital in São Paulo State, Brazil. case series descriptive study with data of medical records from the emergency department of the Municipal Hospital of Itapira-SP, in 2012. out of 3,184 medical cases due to toxicological events (3.3% of total), the exposures to drugs of abuse (58.1%) and accidents with venomous animals (15.8%) stood out; most individuals were male (68.6%), in the age group from 20 to 59 years (74.6%); according to the medical records, 18 cases had been reported to the Information System for Notifiable Diseases (Sinan), however 249 cases were found on Sinan online. the health care profile was characterized by the predominance of exposure to drugs of abuse and accidents with venomous animals in a young adult population; most cases was not notified to Sinan, which may lead to an insufficient acknowledgement on this problem.


A simplified and convenient laboratory-scale preparation of 14N or 15N high molecular weight poly(dichlorophosphazene) directly from PCl5.
A simple and convenient one-pot synthesis of THF solutions of high molecular weight poly(dichlorophosphazene) [NPCl(2)](n), or the (15)N isotopomer [(15)NPCl(2)](n), starting directly from PCl(5) and NH(4)Cl or (15)NH(4)Cl in a solution of 1,2,4-trichlorobenzene in the presence of sulfamic acid and calcium sulfate dihydrate, is described. The solutions of [NPCl(2)](n) in THF, which are obtained free of poly(tetrahydrofuran) by preparing them in the presence of K(2)CO(3), can be reacted directly with phenols, biphenols, or even HO-CH(2)CF(3) in the presence of K(2)CO(3) or Cs(2)CO(3) to obtain, after a very simple workup, the corresponding polyphosphazene derivatives almost free of chlorine.


Compared localizations of prolactin-like and adrenocorticotropin immunoreactivities within the brain of the rat.
By an immunoperoxidase (PAP) technique, ACTH- and prolactin-like substances were detected in neurons of several hypothalamic nuclei in young and adult rats. Neurons in the arcuate and ventromedial nuclei were simultaneously both ACTH-like and PRL-like positive. Labelled fibres were followed to their fields of projections. Intensity of labelling was not influenced by experimental procedures known to change PRL and ACTH content of the pituitary. Colchicine enhanced labelling of perikarya while lowering that of fibres. The results support neuronal synthesis of hormonal ACTH and PRL related molecules and their involvement in the control of autonomic nerve functions.


Competitive amplification of differentially melting amplicons (CADMA) enables sensitive and direct detection of all mutation types by high-resolution melting analysis.
Sensitive and specific mutation detection is of particular importance in cancer diagnostics, prognostics, and individualized patient treatment. However, the majority of molecular methodologies that have been developed with the aim of increasing the sensitivity of mutation testing have drawbacks in terms of specificity, convenience, or costs. Here, we have established a new method, Competitive Amplification of Differentially Melting Amplicons (CADMA), which allows very sensitive and specific detection of all mutation types. The principle of the method is to amplify wild-type and mutated sequences simultaneously using a three-primer system. A mutation-specific primer is designed to introduce melting temperature decreasing mutations in the resulting mutated amplicon, while a second overlapping primer is designed to amplify both wild-type and mutated sequences. When combined with a third common primer very sensitive mutation detection becomes possible, when using high-resolution melting (HRM) as detection platform. The introduction of melting temperature decreasing mutations in the mutated amplicon also allows for further mutation enrichment by fast coamplification at lower denaturation temperature PCR (COLD-PCR). For proof-of-concept, we have designed CADMA assays for clinically relevant BRAF, EGFR, KRAS, and PIK3CA mutations, which are sensitive to, between 0.025% and 0.25%, mutated alleles in a wild-type background. In conclusion, CADMA enables highly sensitive and specific mutation detection by HRM analysis.


TCR extracellular domain genetically linked to CD28, 2B4/41BB and DAP10/CD3ζ -engineered NK cells mediates antitumor effects.
NK cells, especially FDA-approved NK-92 cells, could be used for TCR engineering owing to their specialized cytotoxicity against tumors, safety profile and potential use as an off-the-shelf cellular therapy. The TCR complex requires assembly of TCR- α/ β chains with CD3 molecules (CD3δ, CD3γ, CD3ε, CD3ζ) to be correctly expressed at the cell membrane, and yet NK cells lack expression of these CD3 subunits besides CD3ζ. Since transmembrane regions of TCR α and β chains are involved in TCR complex assembly, transmembrane regions of TCR replaced by CD28 transmembrane domain could result in the expression of TCR independent of its companion CD3 subunits. However, since the absence of CD3 signaling components can influence the transmission of TCR signals to NK cells, it is necessary to add the signaling molecules of NK cells followed by CD28 transmembrane domain. Both CD3ζ and DAP10 play an important role in the activation and cytotoxicity of NK cells; moreover, 2B4 and 4-1BB are the main costimulatory molecules in NK cells. Therefore, we designed a chimeric TCR that consisted of the extracellular domains of the TCR α and β chains specific for NYESO-1 fused to the CD28 transmembrane domain followed by the 41BB and CD3ζ signaling domains as well as the 2B4 and DAP10 signaling domain, respectively. The chimeric TCR genetically engineered NK-92 cells exhibit antigen-specific recognition and lysis of tumor cells both in vitro and in vivo. In addition, TCR-28-2B10/BBζ can be feasibly expressed in primary NK cells and exhibit antigen-reactive recognition and effect function. The overall encouraging data highlight the value of NK-92 cells and primary NK cells engineered to express therapeutic chimeric TCR for adoptive immunotherapies.


The moss bioreactor.
The production of recombinant proteins in moss bioreactors provides all of the benefits of molecular farming in plants but avoids many plant-specific disadvantages, such as the genetic instability of de-differentiated cells in suspension culture or the lack of containment during field production. Protein yields are in the same range as those of other cell-culture-based production systems. On top of this, the moss Physcomitrella patens is the only known plant that can be genetically modified by homologous recombination, allowing efficient targeted gene disruption. Thus, the major drawback of producing human proteins in plants, allergic reactions caused by plant-specific glycosylation, can be diminished by targeted knockout of the responsible genes in moss. Unlike all other plants, moss allows straightforward 'humanisation' of plant-derived pharmaceuticals.


Association of Rhegmatogenous Retinal Detachment Incidence With Myopia Prevalence in the Netherlands.
The incidence of rhegmatogenous retinal detachment (RRD) is partly determined by its risk factors, such as age, sex, cataract surgery, and myopia. Changes in the prevalence of these risk factors could change RRD incidence in the population. To determine whether the incidence of RRD in the Netherlands has changed over recent years and whether this change is associated with an altered prevalence of RRD risk factors. This cohort study included data from all 14 vitreoretinal clinics in the Netherlands, as well as a large Dutch population-based cohort study. All patients who underwent surgical repair for a primary RRD in the Netherlands from January 1 to December 31, 2009, and January 1 to December 31, 2016, were analyzed, in addition to all participants in the population-based Rotterdam Study who were examined during these years. Analysis began February 2018 and ended November 2019. RRD risk factors, including age, male sex, cataract extraction, and myopia. Age-specific RRD incidence rate in the Dutch population, as well as change in RRD incidence and risk factor prevalence between 2009 and 2016. In 2016, 4447 persons (median [range] age, 61 [3-96] years) underwent surgery for a primary RRD within the Netherlands, resulting in an RRD incidence rate of 26.2 per 100 000 person-years (95% CI, 25.4-27.0). The overall RRD incidence rate had increased by 44% compared with similar data from 2009. The increase was observed in both phakic (1994 in 2009 to 2778 in 2016 [increase, 39%]) and pseudophakic eyes (1004 in 2009 to 1666 in 2016 [increase, 66%]), suggesting that cataract extraction could not solely account for the overall rise. Over the same period, the prevalence of mild, moderate, and severe myopia among persons aged 55 to 75 years had increased by 15.6% (881 of 4561 [19.3%] vs 826 of 3698 [22.3%]), 20.3% (440 of 4561 [9.6%] vs 429 of 3698 [11.6%]), and 26.9% (104 of 4561 [2.3%] vs 107 of 3698 [2.9%]), respectively, within the population-based Rotterdam Study. In this study, an increase was observed in primary RRD incidence in the Netherlands over a 7-year period, which could not be explained by a different age distribution or cataract surgical rate. A simultaneous myopic shift in the Dutch population may be associated, warranting further population-based studies on RRD incidence and myopia prevalence.


A monoclonal antibody against an epitope common to HLA-b locus antigens.
A monoclonal antibody G4 that appears to be directed against a determinant common to all HLA-B locus antigens is described. This antibody reacted with a large panel of B and T lymphocyte and cell lines, but it did not react with two lines that do not serologically express HLA antigens (Daudi and K562) and two lines that expressed A-locus but not B-locus antigens (8402 and HPBMLT). The F(ab')2 fragment of G4 blocked B-locus but not A-locus HLA alloantisera. By immunoprecipitation and SDS-polyacrylamide gel electrophoresis G4 reacted with a dimer consisting of a heavy chain of 44,000 daltons and a light chain of 12,7000 daltons.


[Modern face lift surgery].
Face lift surgery is generally considered the classical surgical procedure of plastic surgery. This is an extensive operation which has undergone a huge development since its first implementation more than 100 years ago. What began as a simple skin tightening procedure is today a sophisticated and complex technique which ideally combines different treatment methods planned with surgical precision. This article provides an overview of the history of the procedure to the present state of the art concept of pairing biplanar and bivectorial face-neck lifts with autologous fat transfer and dermabrasion.


Thrombophilia and immunological disorders in pregnancies as risk factors for small for gestational age infants.
To determine if inherited thrombophilia and immunological disorders represent risk factors for small for gestational age infants, and to assess their relationship with neonatal status. Case-control study. Ninety-seven consecutive women who had pregnancies complicated by unexplained small for gestational age infants, defined as a birthweight below the third centile and 97 women as controls who delivered infants with a birthweight > or = 10th centile. Patients were included in the immediate postpartum period and tested for antithrombin III, protein C, protein S, anticardiolipin and antinuclear antibodies, lupus anticoagulant, Factor V Leiden mutation, prothrombin 20210A mutation, and methylenetetrahydrofolate reductase (MTHFR) polymorphism. Women with small for gestational age infants were then divided into subgroups depending on haemostatic and immunologic status in order to compare neonatal events. Frequencies for anticardiolipin and antinuclear antibodies were higher in women with small for gestational age infants compared with controls (P = 0.02 and P = 0.004, respectively), and overall prevalence of inherited thrombophilia were comparable in cases and controls (19.6% and 18.6%, respectively). The subgroups of patients with small for gestational age infants were women with only one inherited thrombophilia (n = 10), only one immunological disorder (n = 14), combined disorders (n = 9), and no detected abnormality (n = 64). Admission to paediatric ward significantly increased in the group with combined disorders (P = 0.002) compared with the other groups. Also one-third of the babies from this group had a poor neonatal outcome. However, most of the neonatal deaths (6/7 = 85.7%) occurred in the group with no detected abnormality. The prevalence of inherited thrombophilia was considered to be similar between the case and the control groups even when immunological disorders were significantly elevated in pregnancies complicated by the baby being small for gestational age. Combined disorders may represent a potential risk factor for severe small for gestational age infants. However, the aetiology of small for gestational age infants with poor neonatal outcomes remains unknown in most cases.


Relationships between pathological patterns and vocal qualities estimated by acoustic parameters.
To examine whether vocal characteristics estimated by acoustic parameters were associated with phlegm, yin deficiency, or cold-heat patterns. A total of 75 college students (males:females = 53:22) aged 19-24 years were enrolled in this study. Each subject was asked to complete the phlegm pattern questionnaire (PPQ), yin deficiency questionnaire (YDQ) and cold-heat questionnaire (CHQ). For the acoustic analysis, each subject was asked to produce a sustained vowel sound (/a/) for 3 s to be used to calculate acoustic parameters. Then, habitual fundamental frequency (F0), jitter, shimmer, F0tremor, mean F0, standard deviation of F0, maximum F0, minimum F0, normalized noise energy, harmonic-to-noise ratio, signal-to-noise ratio, amplitude tremor, and power ratio were calculated using the Dr. Speech software. Finally, four hierarchical regression models with pattern questionnaire scores as dependent variables were formed to examine which factors among acoustic parameters, sex, and age were predictive of those pattern scores. PPQ, YDQ, heat, and cold pattern scores all formed significant regression model equations and the adjusted R2 values were 0.281, 0.164, 0.156, and 0.170, respectively. There were aging effects in the PPQ and YDQ models (standardized β=0.199, 0.271, respectively). Vocal tremor-related F0 tremor and vocal ringing-related power ratio parameters were associated with PPQ and YDQ scores. Gender was directly predictive of PPQ and indirectly moderated the relationship between power ratio and YDQ score. Vocal pitch-related habitual F0 and mean F0 were associated with heat and cold scores. These results indicate that the vocal qualities of phlegm- and yin deficiency-susceptible subjects tend to be ringing and less tremorous, and those of heat- and cold-susceptible subjects tend to be high-pitched. Our study results suggest that vocal characteristics estimated by acoustic parameters are partially predictive of phlegm, yin deficiency, heat, and cold patterns. In terms of phlegm and yin deficiency patterns, there were direct or moderating effects of sex and age.


A fatigue questionnaire (QFES) for child athletes: a four-year follow-up study in young skiers.
The use of a fatigue monitoring questionnaire is an increasingly widespread practice in sports medicine. To evaluate variations in the QFES fatigue questionnaire score according to periods of rest, training or competition. Sixty-six skiers (either alpine or cross-country skiers, aged between 11 and 14 years and training for between 12 and 18 hours per week) filled out a total of 400 fatigue questionnaires over a four-year follow-up period. Our analysis of the QFES fatigue scores showed that only a small proportion of the skiers (5.25%, on average) exceeded the fatigue alert threshold at some point during the longitudinal follow-up; periods of competition correspond to rising fatigue scores, in comparison with the beginning of season and girls always have higher scores than boys (25.32+/-0.90 versus 20.46+/-0.91, respectively; p<0.0002). In contrast, there was no correlation between fatigue levels and the type of skiing discipline practiced. Our main results show that the QFES fatigue questionnaire is a sensitive tool for tracking down particular periods of fatigue (competition, intense training). Even though the mechanism of fatigue is still not fully understood (highlighting the complexity of this syndrome), the systematic use of a fatigue questionnaire when monitoring children performing competitive sport and high volumes of training confirms the possible preventive role of this type of tool.


Acute effect of DMBA application on Langerhans cells of the hamster buccal pouch mucosa.
One, two, and three applications of DMBA in mineral oil to hamster buccal pouch mucosa did not result in obvious histologic alterations in experimental periods ranging from 4 1/2 hours to 2 weeks after the last DMBA application. However, there were significant increases in the number of Langerhans cells, as disclosed histochemically with ATPase staining. There was also an increase in the length and size of the dendritic processes of the Langerhans cells. Applications of DMBA in oil resulted in a consistently significant increase in Langerhans cells when compared to the buccal pouch mucosa of untreated animals. However, mineral oil applications also resulted in a slight increase in Langerhans cells when compared to the mucosa of untreated controls. The major effects of the DMBA on Langerhans cells occurred after 2 weeks and with increasing numbers of applications. The increase in Langerhans cells is interpreted as an enhanced response by immunologically competent cells which may represent an early immune response to the very early changes in carcinogenesis.


Has intraoperative neuromonitoring changed the surgery for unruptured middle cerebral artery aneurysms? A retrospective comparative study.
Intraoperative neurophysiological monitoring (IONM) represents one of the available technologies able to assess ischemia and aimed to improve surgical outcome reducing the treatment related morbidity in surgery for intracranial aneurysms. Many studies analyzing the impact of IONM are poised by the heterogeneity bias affecting the cohorts. We report our experience with IONM for surgery of unruptured middle cerebral artery (MCA) aneurysm in order to highlight its influence on functional and radiological outcome and surgical strategy. We retrospectively reviewed all MCA unruptured aneurysms treated between January 2013 and June 2021 by our institutional neurovascular team. Patients were divided into 2 groups according to the use of IONM. A total of 153 patients were included in the study, 52 operated on without IONM and 101 with IONM. The groups did not differ preoperatively regarding clinical status and aneurysm characteristics. Patients operated with IONM had better functional outcomes at discharge as well as at follow-up (p= 0.048, p=0.041) due to lower symptomatic ischemia and better radiological outcome due to lower rate of unexpected aneurysmal remnants (p= 0.0173). The introduction of IONM changed the use of temporary clipping (TeC), increasing its average duration (p= 0.01) improving the safety of dissecting and clipping the aneurysm. IONM in surgery for unruptured MCA aneurysm could improve the efficacy and safety of clipping strategy in the way it showed a role in changing the use of TeC and was associated to the reduction of unexpected aneurysmal remnants' rate and improvement in both short- and long-term patient's outcome.


Familial lecithin-cholesterol acyltransferase deficiency: biochemical characteristics and molecular analysis of a new LCAT mutation in a Polish family.
Familial LCAT deficiency (FLD) is a rare genetic disorder associated with corneal opacities, anaemia and proteinuria with renal failure. Here we report detailed analyses on plasma lipids, lipoproteins, and the molecular defect in two siblings from a Polish family presenting classical symptoms of FLD and their family members with newly discovered Val309Met mutation in exon 6 of LCAT gene. Both patients displayed low total (2.19 and 2.94 mmol/l) and HDL-cholesterol concentrations (0.52 and 0.48 mmol/l), low percentage of cholesteryl esters (CE) (11.1 and 12%), and decreased apo AI and apo AII serum levels. Low LDL-cholesterol, apo B and Lp(a) levels, and increased oleate/linoleate ratios in CE could be of importance in the development of atherosclerosis in these patients with low HDL-cholesterol. LCAT activity was 10% of normal, alpha-LCAT activity was 0, and LCAT concentration was undetectable by immunoassay. Plasma CETP activity was at lower limits of normal. PCR and sequence analysis of DNA from the proband and affected brother revealed a novel G-->A mutation in exon 6 of LCAT gene, which resulted in an amino acid substitution of valine for methionine (Val309Met). The proband and affected brother were both homozygous carriers, while the mother, siblings and children of patients were heterozygous carriers of a newly discovered mutation. This is the first LCAT mutation described in the Slavic population.


Phosphorus(V) corrole: DNA binding, photonuclease activity and cytotoxicity toward tumor cells.
A new phosphorus(V) corrole, 10-(4-hydroxylphenyl)-5,15-bis(pentafluorophenyl)corrolato (trans-dihydroxo)phosphorus(V) 1-P, was synthesized and characterized. The interaction of 1-P with calf thymus DNA (CT-DNA) was studied by multi-spectroscopic methods. The photonuclease activity of this complex was examined by agarose gel electrophoresis. 1-P may bind to CT-DNA via an outside binding mode and display good photonuclease activity. 1-P displayed low dark toxicity but high photocytotoxic activity against H460 and A549 tumor cell lines.


Utilization and Spending With Preventive Drug Lists for Asthma Medications in High-Deductible Health Plans.
High-deductible health plans with health savings accounts (HDHP-HSAs) incentivize patients to use less health care, including necessary care. Preventive drug lists (PDLs) exempt high-value medications from the deductible, reducing out-of-pocket cost sharing; the associations of PDLs with health outcomes among patients with asthma is unknown. To evaluate the associations of a PDL for asthma medications on utilization, adverse outcomes, and patient spending for HDHP-HSA enrollees with asthma. This case-control study used matched groups of patients with asthma before and after an insurance design change using a national commercial health insurance claims data set from 2004-2017. Participants included patients aged 4 to 64 years enrolled for 1 year in an HDHP-HSA without a PDL in which asthma medications were subject to the deductible who then transitioned to an HDHP-HSA with a PDL that included asthma medications; these patients were compared with a matched weighted sample of patients with 2 years of continuous enrollment in an HDHP-HSA without a PDL. Models controlled for patient demographics and asthma severity and were stratified by neighborhood income. Analyses were conducted from October 2020 to June 2023. Employer-mandated addition of a PDL that included asthma medications to an existing HDHP-HSA. Outcomes of interest were utilization of asthma medications on the PDL (controllers and albuterol), asthma exacerbations (oral steroid bursts and asthma-related emergency department use), and out-of-pocket spending (all and asthma-specific). A total of 12 174 participants (mean [SD] age, 36.9 [16.9] years; 6848 [56.25%] female) were included in analyses. Compared with no PDL, PDLs were associated with increased rates of 30-day fills per enrollee for any controller medication (change, 0.10 [95% CI, 0.03 to 0.17] fills per enrollee; 12.9% increase) and for combination inhaled corticosteroid long-acting β2-agonist (ICS-LABA) medications (change, 0.06 [95% CI, 0.01 to 0.10] fills per enrollee; 25.4% increase), and increased proportion of days covered with ICS-LABA (6.0% [0.7% to 11.3%] of days; 15.6% increase). Gaining a PDL was associated with decreased out-of-pocket spending on asthma care (change, -$34 [95% CI, -$47 to -$21] per enrollee; 28.4% difference), but there was no significant change in asthma exacerbations and no difference in results by income. In this case-control study, reducing cost-sharing for asthma medications through a PDL was associated with increased adherence to controller medications, notably ICS-LABA medications used by patients with more severe asthma, but was not associated with improved clinical outcomes. These findings suggest that PDLs are a potential strategy to improve access and affordability of asthma care for patients in HDHP-HSAs.


Some myths and messages concerning the batch and continuous culture of animal cells.
lt is often assumed that continuous processes are more difficult and less productive than a suite of batch processes for the production of a particular biomolecule. This paper cites two papers which have appeared in the literature which propound this view and examines in detaü the justification for the support of this contention. After reviewing those features where it is alleged that continuous processes are at a disadvantage, the authors of this paper conclude that the opposite is the case and that for suitable processes the most effective way of generating product is by the use of fully continuous processes. The choice of a particular process dependends on a variety of fixed and variable factors which are unique to the process. These factors are discussed and two decision trees are presented which are designed to facilitate the choice of the appropriate process technology.


Onset and remission of common mental disorders among adults living in temporary housing for three years after the triple disaster in Northeast Japan: comparisons with the general population.
People living in temporary housing for long periods after a disaster are at risk of poor mental health. This study investigated the post-disaster incidence and remission of common mental disorders among adults living in temporary housing for the 3 years following the 2011 Great East Japan Earthquake. Three years after the disaster, face-to-face interviews were conducted with 1089 adult residents living in temporary housing in the disaster area, i.e., the shelter group, and a random sample of 852 community residents from non-disaster areas of East Japan. The World Health Organization Composite International Diagnostic Interview was used to diagnose DSM-IV mood, anxiety, and alcohol use disorders. Information on demographic variables and disaster experiences was also collected. Response rates were 49 and 46% for the shelter group and the community residents, respectively. The incidence of mood/anxiety disorder in the shelter group was elevated only in the first year post-disaster compared to that of the general population. The rate of remission for mood and anxiety disorders was significantly lower in the shelter group than in the community residents. The proportion seeking medical treatment was higher in the shelter group. The onset of common mental disorders increased in the first year, but then levelled off in the following years among residents in temporary housing after the disaster. Remission from incident post-disaster mental disorders was slower in the shelter group than in the general population. Post-disaster mental health service could consider the greater incidence in the first year and prolonged remission of mental disorders among survivors with a long-term stay in temporary housing after a disaster.


Ocular neovascularization: an epidemiologic review.
Neovascularization occurs in many eye diseases, and its epidemiologic impact is significant. However, data on the prevalence and incidence of ocular neovascularization have never been compiled to demonstrate its pervasiveness. This overview of ocular angiogenesis provides a review of the epidemiologic literature for neovascularization in various parts of the eye, including the cornea, iris, retina, and choroid. Relevant disease states are reviewed, as are their risk factors, so that their pathogenesis can be better understood. Data on the prevalence and incidence of the major diseases involving angiogenesis are synthesized to provide statistical evidence of the span and magnitude of ocular neovascularization. These prevalence and incidence data on ocular neovascularization are extrapolated to USA population data where possible, and "worst-case" estimates are calculated as well. Information was gathered with a search of the MEDLINE database, published monographs and volumes, and consultation with a number of primary authors. This study attempts to unify much of past and present epidemiologic research, and the information is presented in sections divided according to the anatomy of the eye.


Secretory component-dependent binding of immunoglobulin A in the rat, monkey and human: a comparison of intestine and liver.
The source and significance of immunoglobulin A in bile remains controversial. In the rat, and several other species, immunoglobulin A is transported through hepatocytes by a specific receptor, secretory component. In humans, immunohistochemical methods have indicated a distinct lack of receptors for immunoglobulin A on hepatocytes. Binding assays with 125I-immunoglobulin A and membranes from hepatocytes and intestinal cells of the rat display secretory component-dependent binding. Primate intestinal cells also show secretory component-specific binding of immunoglobulin A. Primate liver, on the other hand, does not show immunoglobulin A binding mediated by the polymeric immunoglobulin receptor.


Management of metallic implants in radiotherapy.
The number of patients with metallic implant and treated with radiotherapy is constantly increasing. These hardware are responsible for the deterioration in the quality of the CT images used at each stage of the radiation therapy, during delineation, dosimetry and dose delivery. We present the update of the recommendations of the French society of oncological radiotherapy on the pros and cons of the different methods, existing and under evaluation, which limit the impact of metallic implants on the quality and safety of radiation treatments.


Procedures to Evaluate Inflammatory and Pathological Changes During Allergic Airway Inflammation.
Cellular inflammation, with elevated levels of Th1/Th2 cytokines, airway mucus hypersecretion, and thickening of the airway smooth muscle, are characteristic features of the allergic lung. Assessment of pathophysiological changes in allergic lungs serves as an important tool to determine disease progression and understand the underlying mechanisms of pathogenesis. This can be achieved by evaluating the lung tissue for inflammation and airway structural changes along with the measurement of important pro-inflammatory mediators such as Th1/Th2 cytokines and eotaxins. This chapter describes procedures to histologically evaluate inflammatory and pathological changes observed during allergic airway inflammation using lung tissue from mice.


Maritime halophyte species from southern Portugal as sources of bioactive molecules.
Extracts of five halophytes from southern Portugal (Arthrocnemum macrostachyum, Mesembryanthemum edule, Juncus acutus, Plantago coronopus and Halimione portulacoides), were studied for antioxidant, anti-inflammatory and in vitro antitumor properties. The most active extracts towards the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical were the methanol extracts of M. edule (IC₅₀ = 0.1 mg/mL) and J. acutus (IC₅₀ = 0.4 mg/mL), and the ether extracts of J. acutus (IC₅₀ = 0.2 mg/mL) and A. macrostachyum (IC₅₀ = 0.3 mg/mL). The highest radical scavenging activity (RSA) against the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical was obtained in the ether extract of J. acutus (IC₅₀ = 0.4 mg/mL) and H. portulacoides (IC₅₀ = 0.9 mg/mL). The maximum total phenolic content (TPC) was found in the methanol extract of M. edule (147 mg gallic acid equivalents (GAE)/g) and in the ether extract of J. acutus (94 mg GAE/g). Significant decreases in nitric oxide (NO) production were observed after incubation of macrophages with lipopolysaccharide (LPS) and the chloroform extract of H. portulacoides (IC₅₀ = 109 µg/mL) and the hexane extract of P. coronopus (IC₅₀ = 98.0 µg/mL). High in vitro cytotoxic activity and selectivity was obtained with the ether extract of J. acutus. Juncunol was identified as the active compound and for the first time was shown to display selective in vitro cytotoxicity towards various human cancer cells.


Long-term effects of benidipine hydrochloride on severe left ventricular hypertrophy and collagen metabolism in patients with essential hypertension.
The long-term effects of benidipine on left ventricular hypertrophy (LVH) and collagen metabolism were examined in patients with essential hypertension. Forty patients with untreated essential hypertension were given benidipine at a dose of 6 mg a day. Routine echocardiographic parameters, serum concentrations of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were analyzed before and 12 months after treatment with benidipine. Patients were classified according to left ventricular mass index (LVMI) into three groups: severe LVH (LVMI > or = 159), mild LVH (159 > LVMI > or = 125) and no LVH (LVMI < 125). Serum levels of free TIMP-1 to MMP-1 ratio were significantly higher in patients with severe LVH than in the other two groups before treatment. There was a significant positive correlation between the free TIMP-1 to MMP-1 ratio and LVMI in all study subjects (r = 0.51, p < 0.01). Twelve months after treatment, percentage changes of the LVMI and free TIMP-1 to MMP-1 ratio were significantly larger in the patients with severe LVH (-27% and -54%) than with mild LVH (-12% and -23%) or no LVH (-4% and -11%), respectively. Changes in the systolic blood pressure but not changes in the free TIMP-1 to MMP-1 ratio correlated with changes in the LVMI in patients with mild LVH (r = 0.78, p < 0.01). Changes in the free TIMP-1 to MMP-1 ratio but not changes in the systolic blood pressure correlated with changes in the LVMI in patients with severe LVH (r = 0.69, p < 0.01). Long-term administration of benidipine reduced left ventricular mass and normalized systemic collagen type I degradation abnormalities in essential hypertensive patients with severe but not mild LVH.