Polystyrene and low-density polyethylene pellets are less effective in arsenic adsorption than uncontaminated river sediment.
The adsorption process of inorganic arsenic (As) plays an important role in its mobility, bioavailability, and toxicity in the river environment. In this work, the adsorption of dissolved arsenite (As(III)) and arsenate (As(V)) by microplastics (MPs) pellets (polystyrene (PS) and low-density polyethylene (LDPE)), river sediment, and their mixture were investigated to assess the adsorption affinities and mechanism. The adsorption kinetics showed slow and mild rising zones from the natural behavior of the chemical adsorption. The results indicated that both MP characteristics and water properties played a significant role in the adsorption behavior of inorganic As species. The As adsorption equilibrium was modeled well by both Langmuir and Freundlich isotherms and partly fitted with the Sips model suggesting that both mono-layer and multi-layer adsorption occurred during adsorption The spontaneous adsorption process for both As(III) and As(V) was evidenced by the adsorption thermodynamics. The maximum adsorption capacities of As(III) and As(V) reached 143.3 mg/kg and 109.8 mg/kg on PS in deionized water, which were higher than those on sediment-PS mixture (119.3 mg/kg, 99.2 mg/kg), which were all lower than on sediment alone (263.3 mg/kg, 398.7 mg/kg). The Fourier transform infrared spectroscopy analysis identified that As(III) and As(V) interaction with sediment surface functional groups was the main adsorption mechanism from surface complexation and coordination. Two functional groups of polystyrene (-NH2, -OH) were mainly involved in the adsorption of inorganic As species on PS, while -COO- and -OH functional groups contributed to the adsorption mechanism of inorganic As species on LDPE. The findings provide valuable insight on the adsorption behavior and mechanisms of As(III) and As(V) in river systems in the presence of MPs particles. Both PS and LDPE were shown to be less effective than river sediment in the adsorption of As species from water, which provides a different perspective in understanding the scale of MPs impact in pollutant transport in the aquatic environment.


Differentiation of hypointense nodules on gadoxetic acid-enhanced hepatobiliary-phase MRI using T2 enhanced spin-echo imaging with the time-reversed gradient echo sequence: An initial experience.
To optimize the flip angle (FA) of the T2 enhanced spin-echo imaging using the time reversed gradient echo (T2FFE) and evaluate its utility for differentiating hypointensity nodules in the hepatobiliary phase (HBP) of gadoxetic acid-enhanced (Gd-EOB) MRI. First, FA optimization of the T2FFE in the HBP was investigated by comparing signal-to-noise ratio (SNR) among different FAs using phantoms. The liver-to-muscle contrast ratios (CRLiver-Muscle) and image quality among three FAs (20°, 50° and 80°) were compared using images of 10 patients. Next, the utility of the T2FFE with an optimized FA for differentiating hypointensity nodules in the HBP was assessed by comparing the lesion-to-liver contrast ratio (CRLesion-Liver) among cysts, hemangiomas, hepatocellular carcinomas, and metastatic tumors in 32 patients. SNR increased as FA increased, but leveled off at FAs of 50° and greater. The FA of 50° showed significantly better image quality scores than that of 80° (p<0.05). After employing an FA of 50°, the CRLesion-Liver value indicated that the T2FFE depicted benign lesions as hyperintense and most malignant lesions as hypointense in relation with the liver parenchyma (p<0.05). The T2FFE in the HBP of Gd-EOB-MRI is useful for differentiating benign and malignant liver lesions.


Homology modeling and consensus protein disorder prediction of human filamin.
Filamins are dimeric actin-binding proteins participating in the organization of the actin-based cytoskeleton. Their modular domain organization is made up of an N-terminal actin-binding domain composed of two CH domains followed by flexible rod regions that consist of 24 Ig-like domains. Homology modeling was used to model human filamin using Modeller 9v5. The resulting model assessed by Verify 3D and PROCHECK showed that the final model is reliable. The conformational disorder prediction of human filamin residues were also mapped on the validated structure of human filamin. Prediction of protein disorder in filamin structures will help structural biologists to find suitable targets to be analyzed and for understanding protein function.


Construction of a breast cancer prognosis model based on alternative splicing and immune infiltration.
Breast cancer (BC) is the most common malignancy among women in the world. Alternative splicing (AS) is an important mechanism for regulating gene expression and producing proteome diversity, which is closely related to tumorigenesis. Understanding the role of AS in BC may be helpful to reveal new therapeutic targets for clinical interventions. RNA-seq, clinical and AS data of TCGA-BRCA were downloaded from TCGA and TCGA SpliceSeq databases. AS events associated with prognosis were filtered by univariate Cox regression. The AS risk model of BC was built by Lasso regression, random forest and multivariate Cox regression. The accuracy of the AS risk model and clinicopathological factors were evaluated by time-dependent receiver operating characteristic (ROC) curves. The significant factors were used to construct the nomogram model. Tumor microenvironment analysis, immune infiltration and immune checkpoint analysis were performed to show the differences between the high and low AS risk groups. The expression differences of genes of AS events constituting the risk model in tumor tissues and normal tissues were analyzed, the genes with significant differences were screened, and their relationship with prognosis, tumor microenvironment, immune infiltration and immune checkpoint were analyzed. Finally, Pearson correlation analysis was used to calculate the correlation coefficient between splicing factors (SF) and prognostic AS events in TCGA-BRCA. The results were imported into Cytoscape, and the associated network was constructed. A total of 21,232 genes had 45,421 AS events occurring in TCGA-BRCA, while 1604 AS events were found to be significantly correlated with survival. The BRCA risk model consisted of 5 AS events, (TTC39C|44853|AT*- 2.67) + (HSPBP1|52052|AP*- 4.28) + (MAZ|35942|ES*2.34) + (ANK3|11845|AP*1.18) + (ZC3HAV1|81940|AT*1.59), which were confirmed to be valuable for predicting BRCA prognosis to a certain degree, including ROC curve, survival analysis, tumor microenvironment analysis, immune infiltration and immune checkpoint analysis. Based on this, we constructed a nomogram prediction model composed of clinicopathological features and the AS risk signature. Furthermore, we found that MAZ was a core gene indicating the connection of tumor prognosis and AS events. Ultimately, a network of SF-AS regulation was established to reveal the relationship between them. We constructed a nomogram model combined with clinicopathological features and AS risk score to predict the prognosis of BC. The detailed analysis of tumor microenvironment and immune infiltration in the AS risk model may further reveal the potential mechanisms of BC recurrence and development.


Farnesol and tyrosol: novel inducers for microbial production of carotenoids and prodigiosin.
This study was performed to elucidate the effects of two fungal quorum sensing molecules (tyrosol and farnesol) on carotenoid synthesis in the yeast Rhodotorula glutinis and prodigioin synthesis in the bacterium Serratia marcencens. Farnesol or tyrosol was directly added to the flask cultures at the beginning (immediately after inoculation with the preculture) of day 1 or the beginning (49th h) of day 3. The results demonstrated that tyrosol supplementation increased the synthesis of carotenoids but farnesol supplementation increased the synthesis of prodigiosin. It was found that adding farnesol or tyrosol into the culture on day 3 compared to day 1 caused more increments in pigment synthesis. The maximum increase (fivefold) in the synthesis of prodigiosin was achieved with 200 μL/L farnesol supplementation, whereas the maximum increase (2.13 fold) in the synthesis of carotenoids was achieved with 4 mg/L tyrosol supplementation. This is the first report about the effects of fungal quorum sensing molecules (farnesol and tyrosol) on the synthesis of carotenoids and prodigiosin in microorganisms. Due to non-human toxicity and low price and of farnesol and tyrosol, these molecules can be used as novel inducers for large-scale production of microbial pigments.


Modelling, simulation and control in a data-rich environment.
This paper describes the use and potential use of mathematical modelling, computer simulation, real-time parameter identification and adaptive feedback control techniques in data-rich clinical environments. We consider a system to be operating in a data-rich environment when measurements of system inputs and outputs are frequently available. Two particular application examples which illustrate the power of these techniques will be examined. The first example that will be described involves the development and testing of a real-time adaptive controller for simultaneous regulation of mean arterial pressure and cardiac output using two drugs. The second application of these techniques involves the real-time control of electrical stimulation for the functional use of paralyzed muscles in neuroprosthetic devices.


[Extracorporeal shockwave lithotripsy and lymph node calcification].
A female patient with calculi in the left kidney and calcified lymph nodes in the vicinity of the left renal pelvis was treated successfully with extracorporeal shock wave lithotripsy. The simultaneous action of the shock waves on the calcified lymph nodes did not cause any alteration of the lymph node structure. Thus a shock-wave treatment can be carried out even in the presence of a calcified lymph node without complications.


Does a frozen embryo transfer ameliorate the effect of elevated progesterone seen in fresh transfer cycles?
To compare the effect of progesterone (P) on the day of trigger in fresh assisted reproduction technology (ART) transfer cycles versus its effect on subsequent frozen embryo transfer (FET) cycles. Retrospective cohort study. Large private ART practice. Fresh autologous and FET cycles from 2011-2013. None. Live birth. A paired analysis of patients who underwent both a fresh transfer and subsequent FET cycle and an unpaired analysis of data from all fresh transfer cycles and all FET cycles were performed. We analyzed 1,216 paired and 4,124 unpaired cycles, and P was negatively associated with birth in fresh but not FET cycles in all analyses. Interaction testing of P and cycle type indicated P had a different association with birth in fresh versus FET cycles. When P was ≥ 2 ng/mL at the time of trigger, live birth was more likely in FET versus fresh cycles in the paired analysis (47% vs. 10%), in the unpaired analysis (51% vs. 14%), and in unpaired, good blastocyst only transfer subgroup (51% vs. 29%). Live birth was similar in FET cycles, with P ≥ 2 ng/mL versus P < 2 ng/mL (51% vs. 49%). Conversely, live birth was lower in fresh cycles, with P ≥ 2 ng/mL versus P <2 ng/mL (15% vs. 45%). Elevated P levels on the day of trigger during the initial fresh cycle were negatively associated with live birth in the fresh transfer cycles but not in subsequent FET cycles. Freezing embryos and performing a subsequent FET cycle ameliorates the effect of elevated P on live-birth rates.


Pediatric athletic asthmatics.
The main goals of this review are to help the reader to recognize the common symptoms and signs of exercise-induced asthma and the common objective tests used to confirm or rule out the diagnosis and to understand that different forms and intensities of exercise have different asthmagenicity. The review also aims to help the reader to recognize some of the theories of exercise-induced asthma's pathogenesis, to recognize management strategies (including medications), and to be able to identify medications placed on the 2008 prohibited list by the World Anti-Doping Agency and their therapeutic exemptions. It is also important to understand that respiratory symptoms associated with exercise are not necessarily asthma and that through safe participation in physical exercise, athletic asthmatics can excel in competitive sports.


Phenotypic and molecular states of IDH1 mutation-induced CD24-positive glioma stem-like cells.
Mutations in IDH1 and IDH2 drive the development of gliomas. These genetic alterations promote tumor cell renewal, disrupt differentiation states, and induce stem-like properties. Understanding how this phenotypic reprogramming occurs remains an area of high interest in glioma research. Previously, we showed that IDH mutation results in the development of a CD24-positive cell population in gliomas. Here, we demonstrate that this CD24-positive population possesses striking stem-like properties at the molecular and phenotypic levels. We found that CD24 expression is associated with stem-like features in IDH-mutant tumors, a patient-derived gliomasphere model, and a neural stem cell model of IDH1-mutant glioma. In orthotopic models, CD24-positive cells display enhanced tumor initiating potency compared to CD24-negative cells. Furthermore, CD24 knockdown results in changes in cell viability, proliferation rate, and gene expression that closely resemble a CD24-negative phenotype. Our data demonstrate that induction of a CD24-positive population is one mechanism by which IDH-mutant tumors acquire stem-like properties. These findings have significant implications for our understanding of the molecular underpinnings of IDH-mutant gliomas.


Psychometric validation of the adapted Traditional Chinese version of the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ).
Low back pain is a common health problem encountered by various populations among different countries. This prospective study aimed to translate and cross-culturally adapt the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) into Traditional Chinese and to assess its validity, reliability and sensitivity in Chinese patients experiencing low back pain. Double forward and single back translation of the JOABPEQ was performed with cross-cultural adaptation. By convenience sampling, the final version of the translated JOABPEQ was administered to Chinese patients attending a specialty outpatient clinic with a history of back pain, followed by the traditional Chinese versions of Oswestry Disability Index (ODI) and Short Form-12 version 2 (SF-12v2). Construct validity of the domains were assessed using Spearman's correlation test. Internal consistency was assessed by Cronbach's alpha (α). Sensitivity of the adapted JOABPEQ was determined by known group comparisons. A total of 100 patients were recruited. The translated JOABPEQ demonstrated excellent overall internal consistency (α: 0.912); and good internal consistency for the domains of Lumbar Function, Walking Ability, Social Life Function and Mental Health (α: 0.811, 0.808, 0.788, and 0.827 respectively). Scores of all domains of the translated JOABPEQ had significant correlations (p < 0.01) with ODI at all domains, as well as with almost all domains of SF-12v2 (p < 0.01-0.05). The translated JOABPEQ was sensitive in detecting differences in patients with/without a history of previous spine surgery, and also between patients with acute/acute on chronic versus chronic pain in specific domains. The Traditional Chinese version of JOABPEQ has satisfactory psychometric properties in general, including adequate clinical and construct validity, and internal consistency in assessing Southern-Chinese patients with low back pain. It is demonstrated as a sensitive outcome measure. The translated JOABPEQ is verified for its use in the local clinical setting for patient assessment and future research.


Spatial modelling of the between-herd infection dynamics of bovine virus diarrhoea virus (BVDV) in dairy herds in Denmark.
According to the current literature BVDV-infected neighbours probably impose a high risk of infection of susceptible cattle herds. In the present study, the objective was to evaluate the risk of a dairy herd changing infection status (from not having persistently infected (PI) animals to having PI-animals) in relation to location and infection status of neighbouring cattle herds in Denmark. In total, 7921 dairy herds were included in the analysis of spatial and non-spatial risk factors. The spatial risk factors were derived based on the cattle herds in the neighbourhood (N=36,639 cattle herds). The neighbourhood was defined as the first order neighbouring cattle herds using a Delauney triangularization. In total, 13.3% of the dairy herds changed herd status to PI-herds during the study period that lasted from January 1, 1995, to June 30, 1996. The risk of becoming a PI-herd was negatively associated with the mean distance to the neighbouring herds (OR=0.7 for an increase of 1 km). Presence of PI-herds in the neighbourhood increased the risk of becoming a PI-herd (OR=1.37, 1.40, 1.70 for 1, 2, ≥3 PI-herds in the neighbourhood). Increasing herd size increased the risk of becoming a PI-herd (OR=3.9 for an increase of 10 cows). Regional differences were seen.


Cerebellar hemorrhage in the term neonate: developmental and neurologic outcome.
To elucidate the effects of cerebellar hemorrhage on the term neonate, neurodevelopmental assessments were conducted at a mean age of 32 months on six children. In addition to cerebellar hemorrhage, ventriculomegaly was present on each subject's initial computed tomographic scan. All were managed without surgical evacuation. Two patients required shunts for progressive ventriculomegaly. Five patients had follow-up computed tomography indicating mild atrophy of the superior anterior vermis of the cerebellum; however, none had abnormal ventricular size or abnormalities of the cerebrum. On detailed examination conducted between the ages of 18 and 48 months, five had hypotonia, truncal ataxia, and intention tremor; two had nystagmus. Only one patient walked independently. Intellectual performance of four patients was within the retarded range and two had mildly delayed development. Two patients had markedly disordered expressive language. These data suggest that term neonates surviving cerebellar hemorrhage have neurologic deficits related to the site of hemorrhage, and cognitive deficits related to more generalized cerebral insult.


Planning for ambulatory care: simple methods for improving patient flow.
A combined patient flow and work sampling study was done at the Ambulatory Pediatric Service of the Medical University of South Carolina. The biggest problem was that almost two thirds of the patient's time was spent waiting to see the doctor. Reasons for delay included too few examining rooms, the single block appointment system, and design of the facility.


Racial/Ethnic Differences in Unintended Pregnancy: Evidence From a National Sample of U.S. Women.
Racial and ethnic minorities experience greater burden of unintended pregnancy in the U.S. This study examined the factors associated with racial and ethnic disparities in unintended pregnancy among women in the U.S. using the social ecological model. This study utilized the National Survey of Family Growth data from 2006 to 2010. Data were analyzed in Autumn 2014 and Winter 2015. Decomposition analyses examined which intrapersonal, interpersonal, institutional, community, and public policy factors explained racial and ethnic disparities in unintended pregnancy. Unadjusted analyses found that black and Hispanic women had a greater likelihood of unintended pregnancy compared with white women. Decomposition models explained 51% of the disparity in unintended pregnancy between black and white women and 73% of that between Hispanic and white women. Factors contributing to the disparity between black and white women included age, relationship status, respondent's mother's age at first birth, Federal Poverty Level, and insurance status. Between Hispanic and white women, these factors included age, U.S.-born status, education, and relationship status. Given that the results showed factors at different levels of the social ecological model contribute to racial and ethnic disparities in unintended pregnancy, interventions that aim to reduce these disparities should target at-risk groups of women such as younger, unmarried, lower-income, less-educated, non-U.S. born women and uninsured or publicly insured women.


Effect of Disease Severity in Asthma and Chronic Obstructive Pulmonary Disease on Inhaler-Specific Inhalation Profiles Through the ELLIPTA® Dry Powder Inhaler.
Two studies were undertaken to characterize the maximal effort inhalation profiles of healthy subjects and patients with asthma or chronic obstructive pulmonary disease (COPD) through a moderate-resistance dry powder inhaler (DPI). Correlations between inhaler-specific inhalation characteristics and inhaler-independent lung function parameters were investigated. Healthy subjects (n = 15), patients with mild, moderate, or severe asthma (n = 45), and patients with mild, moderate, severe, or very-severe COPD (n = 60) were included in the studies. Inhalation pressure drop versus time profiles were recorded using an instrumented ELLIPTA® DPI or bespoke resistor component with equivalent resistivity. Inhaler-independent lung function assessments included pharyngometry, spirometry, plethysmography, and diffusion. For the inhaler-specific inhalation profiles, the mean maximal effort peak inspiratory flow rates (PIFRs) varied across the subgroups from 65.8-110.6 L/min (range: 41.6-142.9). Peak pressure drop, PIFR, inhaled volume, and average inhalation flow rate (primary endpoints) did not differ markedly between healthy subjects and patients with asthma or mild COPD. Moderate, severe, and very-severe COPD patients demonstrated lower mean peak pressure drops, PIFRs and inhaled volumes, which tended to decrease with increasing COPD severity. Severe and very-severe COPD patients demonstrated shorter mean inhalation times compared with all other participants. Inhaler-independent lung function parameters were consistent with disease severity, and statistically significant (p < 0.05) strong correlations (R > 0.7) with components of the inhaler-specific inhalation profiles were observed in the COPD cohort; correlations in the asthma cohort tended to be weaker. All participants achieved a maximal effort PIFR ≥ 41.6 L/min through the moderate resistance of the ELLIPTA inhaler. Patients with asthma achieved similar inhalation profiles to healthy subjects, but increasing COPD severity tended to reduce a patient's inhalation capability. Correlation analyses suggest that some lung function parameters may be a useful indicator of ability to inhale efficiently through a moderate-resistance DPI, such as the ELLIPTA inhaler.


The future of contraception: the future leaders of family planning.
The University of California, San Francisco, initiated a Fellowship in Family Planning in 1991, and since then 23 academic teaching hospitals across the country have adopted the 2 year program model for training obstetrician-gynecologist physicians in a subspecialty focused on contraception and abortion. The program follows a curriculum that includes clinical practice, research, and international work. This review includes information about the Fellowship in Family Planning as well as research opportunities available from academia, independent foundations, and government related sources.


Polypropylene suture stresses after closure of longitudinal arteriotomy.
This study was performed (1) to determine the load on polypropylene (Prolene) sutures when used to close a longitudinal carotid arteriotomy and (2) to compare that load with the tensile strength of the suture material. Laboratory methods were used to determine the stress caused by pressure, the surgeon's knot, and that resulting from longitudinal extension of the sutured vessel. Results showed that the stress from the surgeon's knot accounts for more than 95% of total load on the suture, the remainder resulting from pressure and geometry. At 100 mm Hg in a 10 mm carotid artery at in situ length, 5-0 Prolene suture is loaded to 22%, 6-0 to 32%, and 7-0 to 42% of their respective breaking stresses. When the cervical spine is hyperextended, the carotid artery is stretched up to 6%. When the sutured pressurized vessel is extended 6%, 5-0 Prolene suture is loaded to 51%, 6-0 to 52%, and 7-0 to 75% of breaking stresses. These data suggest that 5-0 and 6-0 Prolene sutures should be used in preference to 7-0 sutures to close a carotid arteriotomy.


Fabrication of two-layer poly(dimethyl siloxane) devices for hydrodynamic cell trapping and exocytosis measurement with integrated indium tin oxide microelectrodes arrays.
The design, fabrication and test of a microfluidic cell trapping device to measure single cell exocytosis were reported. Procedures on the patterning of double layer template based on repetitive standard photolithography of AZ photoresist were investigated. The replicated poly(dimethyl siloxane) devices with 2.5 μm deep channels were proved to be efficient for stopping cells. Quantal exocytosis measurement can be achieved by targeting single or small clumps of chromaffin cells on top of the 10 μm × 10 μm indium tin oxide microelectrodes arrays with the developed microdevice. And about 72 % of the trapping sites can be occupied by cells with hydrodynamic trapping method and the recorded amperometric signals are comparable to the results with traditional carbon fiber microelectrodes. The method of manufacturing the microdevices is simple, low-cost and easy to perform. The manufactured device offers a platform for the high throughput detection of quantal catecholamine exocytosis from chromaffin cells with sufficient sensitivity and broad application.


Harvesting of Microcystis flos-aquae using dissolved air flotation: The inhibitory effect of carboxyl groups in uronic acid-containing carbohydrates.
Harvesting algal biomass reduces nutrient loading in eutrophicated lakes and the protein-rich microalgal biomass could be recycled as feedstocks of feed and fertilizer. Due to the complexity of algogenic organic matter (AOM), the key components and functional groups in AOM that inhibit coagulation-based microalgal harvesting have not been disclosed thus far. This study quantitatively analysed the responsive compositions and functional groups of AOM involved in the dissolved air flotation (DAF) harvesting of M. flos-aquae with 1 × 109 cell L-1 density at coagulation pH 6.2. The results showed that harvesting efficiency dropped drastically from 95.5 ± 0.7% to 43 ± 0.7% in the presence of AOM (26.77 mg L-1) at the coagulant dosage of 0.75 mg L-1 and further deteriorated with increasing AOM concentration. Carbohydrates contributed 81% of the total composition of substances involved in the DAF, while the contribution of protein and humic-like substances were only 18% and 1%, respectively. Stoichiometric analysis of functional groups in carbohydrates, proteins, and humic-like substances using model components revealed that carboxyl groups in uronic acid-containing carbohydrates accounted for 76% of the total reduction in carboxyl groups, which was much higher than that in proteins (23%) and humic-like substances (1%), indicating that carboxyl groups in uronic acids containing carbohydrates were the major inhibitors. A conceptual model of charge competition was proposed to explain the inhibition mechanism of carboxyl functional groups in uronic acid-containing carbohydrates on microalgal DAF. Strategies such as preventing carboxyl deprotonation by pH reduction and employment of sweeping/bridging polymeric coagulants/flocculants were proposed for the to reduce the inhibitory effect of carboxyl functional groups.


Efficacy of elbasvir/grazoprevir therapy in HCV genotype-1 with or without HIV infection: role of HCV core antigen monitoring and improvement of liver stiffness and steatosis.
The combination of elbasvir and grazoprevir (EBR/GZR) has been approved for treating HCV infection. This study aimed to evaluate the efficacy of EBR/GZR in terms of sustained virological response (SVR) and improvement of liver fibrosis in Thai patients with HCV genotype-1 (GT1). The utility of serum HCV core antigen (HCVcAg) as an alternative to HCV RNA in assessing SVR was also investigated. A total of 101 HCV GT1-infected patients (65 monoinfection and 36 HIV coinfection) who received EBR/GZR for 12-16 weeks were included. Liver stiffness (LS) and controlled attenuation parameter (CAP) were measured by transient elastography. Serum HCVcAg was measured in parallel with HCV RNA. The overall SVR12 and SVR24 rates in the cohort were 98.0% and 95.0%, respectively. SVR24 rates were consistently high (90.0% to 100%) across all subgroups of patients. A significant LS decline ³30% was observed more frequently in cirrhotic than non-cirrhotic individuals who achieved SVR (63.3% versus 30.3%; P=0.003). The magnitude of LS decline following HCV eradication was comparable between HCV monoinfection and HCV-HIV coinfection. The reduction of CAP was also observed in responders who had significant steatosis at baseline. Compared with HCV RNA, HCVcAg testing displayed high sensitivity (100%) and specificity (99.0-100%) in determining SVR12 and SVR24. This study confirms that EBR/GZR is effective for HCV GT1-infected Thai patients with or without HIV infection. HCV eradication is associated with LS and CAP improvement regardless of HIV status. HCVcAg testing could be a potential replacement for HCV RNA for assessing SVR in resource-limited settings.


Effect of Early Swimming on the Behavior and Striatal Transcriptome of the Shank3 Knockout Rat Model of Autism.
Autism spectrum disorder (ASD) is a developmental disorder characterized by social behavior deficits and stereotyped behaviors in childhood that lacks satisfactory medical intervention. Early swimming intervention is a noninvasive method combining enriched environment and exercise, which has been proven to improve brain development in young children and to treat neurodevelopmental diseases. In this study, we tested the autism-like behavior of rats with deletions in exons 11-21 of the Shank3 gene and evaluated the effect of early swimming intervention (from postnatal day 8 to 60) on the behavior of this animal model of autism. In addition, the transcriptomes of the striatal tissues of wild-type, Shank3 knockout and Shank3 knockout swimming groups rats were analyzed. Shank3 knockout rats exhibit core symptoms of autism, and early swimming improved the social and stereotyped behaviors in this autism rat model. Transcriptomics results revealed that compared to the wild-type group, 291 differentially expressed genes (DEGs) were identified in the striatum of the Shank3 knockout group. Compared to Shank3 knockout group, 534 DEGs were identified in the striatum of Shank3 knockout swimming group. The DEGs annotated by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway shows that the impacts of Shank3 deletion were primarily reflected in synaptic structure, development, morphology, receptor function and signaling, and swimming primarily changed the terms related to the synapses in the striatum of Shank3 knockout rats, including the morphology, structure, composition, development and regulation of synapses. Early swimming intervention can ameliorate behavioral abnormalities caused by Shank3 knockout, by a mechanism that may involve the process of striatal synaptic development and should be further investigated.


Structural studies reveal that the diverse morphology of beta(2)-microglobulin aggregates is a reflection of different molecular architectures.
Amyloid deposition accompanies over 20 degenerative diseases in human, including Alzheimer's, Parkinson's, and prion diseases. Recent studies revealed the importance of other type of protein aggregates, e.g., non-specific aggregates, protofibrils, and small oligomers in the development of such diseases and proved their increased toxicity for living cells in comparison with mature amyloid fibrils. We carried out a comparative structural analysis of different monomeric and aggregated states of beta(2)-microglobulin, a protein responsible for hemodialysis-related amyloidosis. We investigated the structure of the native and acid-denatured states, as well as that of mature fibrils, immature fibrils, amorphous aggregates, and heat-induced filaments, prepared under various in vitro conditions. Infrared spectroscopy demonstrated that the beta-sheet compositions of immature fibrils, heat-induced filaments and amorphous aggregates are characteristic of antiparallel intermolecular beta-sheet structure while mature fibrils are different from all others suggesting a unique overall structure and assembly. Filamentous aggregates prepared by heat treatment are of importance in understanding the in vivo disease because of their stability under physiological conditions, where amyloid fibrils and protofibrils formed at acidic pH depolymerize. Atomic force microscopy of heat-induced filaments represented a morphology similar to that of the low pH immature fibrils. At a pH close to the pI of the protein, amorphous aggregates were formed readily with association of the molecules in native-like conformation, followed by formation of intermolecular beta-sheet structure in a longer time-scale. Extent of the core buried from the solvent in the various states was investigated by H/D exchange of the amide protons.


Efficacy of COVID-19 control measures on post-vaccination outbreak in Italian Long Term Care Facilities: implications for policies.
Numerous individual and organizational factors can influence the spread of SARS-CoV-2 infection in Long Term Care Facilities (LTCFs). A range of outbreak control measures are still implemented in most facilities involving administrations, staff, residents and their families. This study aims to evaluate which measure could influence the transmission of SARS-CoV-2 infection among residents during the period March 2021-June 2022. We enrolled 3,272 residents aged ≥60 years. The outbreak control measures adopted to prevent or manage the infection included entry regulations, contact-regulating procedures, and virological surveillance of residents and staff. The association between LTCFs' and participants' characteristics with new cases of COVID-19 infections was analyzed using multilevel logistic regression models. In 33.8% of the facilities 261 cases of SARS-CoV-2 infection were reported. Among participant characteristics, gender and age were not associated with SARS-CoV-2 infection, while having received the vaccine booster dose was protective against infection [Odds Ratio (OR) = 0.34, 95% Confidence Interval (CI) 0.12-0.99, p = 0.048]. In addition, the implementation of protected areas for family visits was associated with a significant reduction of the probability of infections (OR = 0.18, 95% CI 0.03-0.98, p = 0.047). Overall, about 66% of the variability in the probability of SARS-CoV-2 infection during the observational period may be due to facility structure characteristics and 34% to the participant characteristics. These data showed that vaccination booster doses and family visit restriction-control are still needed to make the LTCFs safer against SARS-CoV-2 infection.


Influence of photodynamic therapy, different final irrigants, and ultrasonic activation on the bond strength of glass fiber posts to root dentin.
To evaluate the influence of photodynamic therapy (PDT), different final irrigants, and ultrasonic activation (US) on the bond strength of glass fiber posts (GFP) to root dentin. One hundred twenty bovine roots were divided into 12 groups according to PDT application, the type of final endodontic irrigant, and US. The samples were divided into 12 groups (n = 10): G1-DW(distilled water); G2-DW+US; G3-17% EDTA; G4-17% EDTA+US; G5-17% GA (glycolic acid); G6-17% GA+US; G7-PDT+DW; G8-PDT+DW+US; G9-PDT+17% EDTA; G10-PDT+17% EDTA+US; G11-PDT+17% GA; G12-PDT+17% GA+US. After cementing the glass fiber posts with resin cement, roots were sectioned into 2-mm-thick slices. One slice from the cervical third and another from the middle third were used for the push out test (PO), and the other two for the diametral compression test (DC). Thus, 10 samples were obtained per third for each mechanical test (n = 10). Kruskal-Wallis and Student-Newman-Keuls tests were used to analyze PO and DC data, and Pearson's correlation test was used to verify the relationship between the variables. Failure patterns were analyzed with chi-square test. Significant differences were found in the PO test among the experimental groups (p < 0.001; power=1.00). PDT improved bond strength when using EDTA. PDT and US increased bond strength when using GA. Favorable failure patterns occurred more frequently in Group GA+US. There was no correlation between data obtained with PO and DC tests (r = 0.112; p = 0.729). PDT provided the highest bond strength values of GFP to root dentin when associated with GA and US or when associated only with EDTA.


Type II nuclear hormone receptors, coactivator, and target gene repression in adipose tissue in the acute-phase response.
The acute-phase response (APR) leads to alterations in lipid metabolism and type II nuclear hormone receptors, which regulate lipid metabolism, are suppressed, in liver, heart, and kidney. Here, we examine the effect of the APR in adipose tissue. In mice, lipopolysaccharide produces a rapid, marked decrease in mRNA levels of nuclear hormone receptors [peroxisome proliferator-activated receptor gamma (PPARgamma), liver X receptor alpha (LXRalpha) and LXRbeta, thyroid receptor alpha (TRalpha) and TRbeta, and retinoid X receptor alpha (RXRalpha) and RXRbeta] and receptor coactivators [cAMP response element binding protein, steroid receptor coactivator 1 (SRC1) and SRC2, thyroid hormone receptor-associated protein, and peroxisome proliferator-activated receptor gamma co-activator 1alpha (PGC1alpha) and PGC1beta] along with decreased expression of target genes (adipocyte P2, phosphoenolpyruvate carboxykinase, glycerol-3-phosphate acyltransferase, ABCA1, apolipoprotein E, sterol-regulatory element binding protein-1c, glucose transport protein 4 (GLUT4), malic enzyme, and Spot14) involved in triglyceride (TG) and carbohydrate metabolism. We show that key TG synthetic enzymes, 1-acyl-sn-glycerol-3-phosphate acyltransferase-2, monoacylglycerol acyltransferase 1, and diacylglycerol acyltransferase 1, are PPARgamma-regulated genes and that they also decrease in the APR. In 3T3-L1 adipocytes, tumor necrosis factor-alpha (TNF-alpha) significantly decreases PPARgamma, LXRalpha and LXRbeta, RXRalpha and RXRbeta, SRC1 and SRC2, and PGC1alpha and PGC1beta mRNA levels, which are associated with a marked reduction in receptor-regulated genes. Moreover, TNF-alpha significantly reduces PPAR and LXR response element-driven transcription. Thus, the APR suppresses the expression of many nuclear hormone receptors and their coactivators in adipose tissue, which could be a mechanism to coordinately downregulate TG biosynthesis and thereby redirect lipids to other critical organs during the APR.


Microdialysis as an approach to quantitate the release of neuropeptides.
1. In vivo microdialysis was performed on anesthetized and awake rats to measured release of cholecystokinin from the posterior nucleus accumbens. 2. Basal levels of cholecystokinin were detectable by radioimmunoassay in some, but not all animals. 3. Recovery through the microdialysis probe ranged from 0.1-2.4% for cholecystokinin, suggesting practical limitations to this approach with present technology.


MicroRNA200a enhances antitumor effects in combination with doxorubicin in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is often treated with doxorubicin. MicroRNAs have been shown to have important regulatory roles in cancer and serve as a target in chemoresistance. In this study, we investigated the effects of specific microRNA-200a (miR-200a) on HCC tumor cell growth and effect of doxorubicin-mediated cytotoxicity. Our results show miR-200a is downregulated in human HCC and HCC tumor cell lines. Increasing miR-200a expression inhibited HCC growth and synergized with the antitumor effects of doxorubicin. Inhibiting endogenous miR-200a promoted tumor growth and chemotherapeutic resistance. Increasing miR-200a expression inhibited tumor metabolism (ATP production, mitochondrial respiration, glycolysis), while inhibition of endogenous miR-200a reversed these effects. MiR-200a expression also increased autophagy and synergized with doxorubicin-mediated cytotoxicity. This study identifies a novel role of miR-200a in potentiating doxorubicin-mediated therapeutic effects in HCC.


Long term outcome of Selective Dorsal Rhizotomy for the management of childhood spasticity-functional improvement and complications.
Selective dorsal rhizotomy (SDR) for the management of lower extremity spasticity is a surgical technique that has existed since the 1900s. While much evidence supports its efficaciousness in reducing tone in the short term, limited information exists detailing the long-term outcome and evolution over time of patients undergoing SDR. All publications with 10 years or more of outcome data on patients undergoing SDR were identified from Medline and Embase databases using the search term "Rhizotmy." Only publications that were in English included patients with cerebral palsy under the age of 21 and discussed SDR for lower extremity spasticity were included. Case reports, reviews without primary data, or publications not accessible online were excluded from the review. A total of 2128 publications were initially identified, of which 19 papers describing 1054 patients fit inclusion and exclusion criteria. GMFCS in most patients improved or remained stable over time after surgery, although durability of improvement and final outcome was dependent on initial functional status. Tone was noted to also substantially improve although a small proportion required additional oral or injectable pharmacologic agents and an even smaller proportion required baclofen pumps. Upper extremity function was also noted to improve substantially after SDR. A significant number of patients were independent for activities of daily living and were engaged in secondary education or gainful employment. A significant proportion of patients still required orthopedic surgery to the lower extremities after SDR, although the incidence of spinal deformity was not observed to be substantially elevated over that of natural history. SDR offers substantial improvements to a number of domains beyond pure tone reduction. These changes are durable over time, although patient selection is crucial in identifying those patients that will have the most benefit. Long-term follow-up is in important in this population given the potential need for further interventions that still exist in many patients.


The Impact of E-diaries and Accelerometers on Young Adults' Perceived and Objectively Assessed Physical Activity.
E-diaries and accelerometers promise more objective, real-time measurements of health behavior. However, social-psychological theory suggests that using electronic behavioral monitoring may influence rather than just record physical activity (PA), especially when a device is novel. Participants (n=146) were randomly assigned to either an accelerometer-only, e-diary-only, accelerometer+e-diary, or a no-technology control group for one week to assess how these technologies influenced PA, both perceived and actual, in young adults. Participants reported their PA, overall and number of discrete exercise sessions (DES) at baseline and follow-up; accelerometers provided daily step counts and e-diaries captured daily reports of PA for the active week of the study. Average daily steps in the accelerometer-only and accelerometer+e-diary groups did not differ nor did daily reports of PA via e-diary compared to accelerometer+e-diary group, showing that neither technology affected actual PA. ANCOVAS tested group differences in perceived PA; The accelerometer-only group had increased perceived overall PA but not DES compared to no-technology control. Accelerometers may increase perceived overall PA, but the tested technologies did not increase DES or actual PA, suggesting that they may be viable unbiased measures of PA.


Planned simultaneous bilateral cochlear implant operations: how often do children receive only one implant?
The aim of this study was to determine the proportion of planned simultaneous cochlear implant operations that do not result in simultaneous cochlear implants on the day of surgery. The frequency with which this occurs has not been reported in the literature, and such information is important for parents' pre-operative decision making. A retrospective review was conducted of pediatric cochlear implant operations performed in the period January 2007-July 2010 at the Melbourne Cochlear Implant Clinic. The number of planned simultaneous cochlear implant procedures and the results of these surgeries were catalogued. Reasons for not proceeding with simultaneous cochlear implants as planned were also identified. In the time period examined, there were a total of 50 planned simultaneous cochlear implant operations. Of these planned simultaneous operations, 22% did not result in bilateral cochlear implants on the day of surgery, with all children involved receiving a first-side cochlear implant only. In the majority of cases, the reason for a first-side cochlear implant only was otitis media. In the time period examined, a considerable proportion of planned simultaneous cochlear implant operations did not result in simultaneous bilateral implantation on the day of surgery. It is important that the likelihood of this outcome is discussed with families during pre-operative counseling as it may influence their decision making.


Heartworm infection.
Dirofilaria immitis is an epizootic filarial parasite that most often infects domestic dogs. This article provides information about the life cycle of Dirofilaria immitis as well as the epidemiology, diagnosis, clinical signs, and treatment of heartworm infection.


Applications of multi-omics analysis in human diseases.
Multi-omics usually refers to the crossover application of multiple high-throughput screening technologies represented by genomics, transcriptomics, single-cell transcriptomics, proteomics and metabolomics, spatial transcriptomics, and so on, which play a great role in promoting the study of human diseases. Most of the current reviews focus on describing the development of multi-omics technologies, data integration, and application to a particular disease; however, few of them provide a comprehensive and systematic introduction of multi-omics. This review outlines the existing technical categories of multi-omics, cautions for experimental design, focuses on the integrated analysis methods of multi-omics, especially the approach of machine learning and deep learning in multi-omics data integration and the corresponding tools, and the application of multi-omics in medical researches (e.g., cancer, neurodegenerative diseases, aging, and drug target discovery) as well as the corresponding open-source analysis tools and databases, and finally, discusses the challenges and future directions of multi-omics integration and application in precision medicine. With the development of high-throughput technologies and data integration algorithms, as important directions of multi-omics for future disease research, single-cell multi-omics and spatial multi-omics also provided a detailed introduction. This review will provide important guidance for researchers, especially who are just entering into multi-omics medical research.


The effects of chronic fluoxetine treatment on chronic mild stress-induced cardiovascular changes and anhedonia.
Depression has a complex bidirectional association with heart disease. Previously we have shown notable cardiovascular changes in the chronic mild stress (CMS) rodent model of depression. Here we investigated the effects of a serotonin-specific reuptake inhibitor on a behavioral index of depression (anhedonia) and cardiac function in rats exposed to CMS. Male Sprague-Dawley rats were exposed to either 4 weeks of control conditions or CMS, consisting of unpredictable periods of mild stressors, while being treated concurrently with 4 weeks of daily fluoxetine (10 mg/kg, sc) or vehicle. Chronic fluoxetine treatment prevented anhedonia in rats exposed to CMS, versus the CMS group treated with vehicle. However, treatment with fluoxetine in the CMS group only partially prevented specific cardiovascular changes associated with CMS, including elevated resting heart rate (HR), exaggerated pressor and HR responses to air jet stress, reduced cardiac output and stroke volume, and HR exaggerated responses to beta-adrenergic receptor blockade. These findings provide evidence that 4 weeks of fluoxetine treatment can prevent behavioral responses and can partially prevent cardiovascular changes associated with CMS, providing insight into the role of serotonin in the link between depression and cardiovascular dysfunction.


Translational opportunities for broad-spectrum natural phytochemicals and targeted agent combinations in breast cancer.
Breast cancer (BC) prevention and therapy in the context of life-style risk factors and biological drivers is a major focus of developmental therapeutics in oncology. Obesity, alcohol, chronic estrogen signaling and smoking have distinct BC precipitating and facilitating effects that may act alone or in combination. A spectrum of signaling events including enhanced oxidative stress and changes in estrogen-receptor (ER)-dependent and -independent signaling drive the progression of BC. Breast tumors modulate ERα/ERβ ratio, upregulate proliferative pathways driven by ERα and HER2 with a parallel loss and/or downregulation of tumor suppressors such as TP53 and PTEN which together impact the efficacy of therapeutic strategies and frequently lead to emergence of drug resistance. Natural phytochemicals modulate oxidative stress, leptin, integrin, HER2, MAPK, ERK, Wnt/β-catenin and NFκB signaling along with regulating ERα and ERβ, thereby presenting unique opportunities for both primary and combinatorial interventions in BC. In this regard, this article focuses on critical analyses of the evidence from multiple studies on the efficacy of natural phytochemicals in BC. In addition, areas in which the combinations of such effective natural phytochemicals with approved and/or developing anticancer agents can be translationally beneficial are discussed to derive evidence-based inference for addressing challenges in BC control and therapy.


Chemical short-range order in liquid Ni-Cu.
Neutron diffraction in combination with isotopic substitution on the zero-scatterer62Ni4363Cu57shows indications for chemical short-range order in the stable liquid as evidenced by oscillations in the concentration-concentration structure factorSCC(q). This points towards a non-ideal solution behavior of Ni-Cu contrary to common believe but in agreement with measurements of free enthalpy of mixing. The temperature dependence ofSCCat small momentum transfer provides evidence of critical compositional fluctuations in Ni43Cu57melts.


Synergistic effects of betel quid chewing, tobacco use (in the form of cigarette smoking), and alcohol consumption on the risk of malignant transformation of oral submucous fibrosis (OSF): a case-control study in Hunan Province, China.
Oral submucous fibrosis (OSF) is a potentially malignant disorder, wherein 7% to 13% of patients with OSF develop oral squamous cell carcinoma (OSCC) at clinically coincident sites established to have OSF. We aimed at investigating the lifestyle-related risk factors for malignant transformation of OSF. A case-control study was conducted among 80 cases with OSF-associated OSCC and 80 controls with OSF but without clinically or histopathologically evident OSCC, recruited from January 2012 to October 2014 in the Xiangya Hospital, Hunan Province, Mainland China. The odds ratios (OR) for OSCC were 13.3 (95% confidence interval [95% CI]: 3.1-56.4) and 45.1 (95% CI: 9.6-212.9) at the highest exposure of betel quid (BQ) chewing, by duration and frequency, respectively. Higher risks were also found to be associated with the consumption of cigarette (OR = 5.0, 95% CI: 1.7-14.8) and alcohol (OR = 3.1, 95% CI: 1.1-8.6). Adjusted ORs increased substantially among patients who consumed BQ and cigarette or alcohol simultaneously, which were 26.1 (95% CI: 4.0-172.6) and 55.-(95% CI: 1.8-1742.8) at the longest duration, and 160.3 (95% CI: 18.7-11371.2) and 58.1 (95% CI: 2.4-1434.9) at the highest dose, respectively. The use of BQ, cigarette, and alcohol were identified as risk factors for malignant transformation of OSF in the Hunan province, Mainland China. Synergistic effects between BQ chewing and cigarette or alcohol consumption were revealed.


Localization of two antigenic determinants in histone H4.
Four overlapping synthetic peptides corresponding to the carboxy-terminal region 80-102 of histone H4 were prepared by solid-phase peptide synthesis. Their antigenic activity was analysed by inhibition of the H4-anti-H4 reaction in complement fixation and enzyme-linked immunosorbent assay. One antigenic determinant was localized in residues 88-96 of the H4 molecule. No antigenic activity was found in peptides 80-89 and 97-102. Antibodies induced by peptide 85-102 were found to bind to free H4 in solution but not to chromatin subunits, suggesting a lack of accessibility of the C-terminal region of H4 in nucleosomes. A second epitope was found to be situated in the N-terminal region 1-53 of histone H4.


A fast highly sensitive colorimetric enzyme immunoassay system demonstrating benefits of enzyme amplification in clinical chemistry.
A method for greatly enhancing the sensitivity of assays employing enzyme labels is described which offers advantages in assays for a wide range of analytes. The principle of the new approach is that the enzyme label gives rise to a catalytic activator for a specific secondary detection system, the activity of which is measured and related back to the amount of label present and thus of the analyte it is being used to determine (C.H. Self, Eur. Pat. Appl. 80303478.4, 15.4.81 exclusively licenced to IQ (Bio) Ltd.). The general principle of enzyme amplification is illustrated by using alkaline phosphatase as the labelling enzyme and nicotinamide adenine dinucleotide phosphate (NADP) as its substrate. The nicotinamide adenine dinucleotide (NAD) formed catalytically activates a strictly NAD specific redox cycle which produces a coloured formazan as the end product. The measured absorbance is at least two orders of magnitude greater than that achieved by conventional methods. The application of this method to immunoassay is demonstrated by a sensitive, rapid and precise assay for human prostatic acid phosphatase (PAP). Some of the many other applications of this methodology are discussed.


S. aureus Toxins Join the DARC Side.
Staphylococcus aureus, like other bacterial pathogens, scavenges host iron for growth through incompletely understood mechanisms. In this issue of Cell Host & Microbe, Spaan et al. (2015) demonstrate that two Staphylococcus aureus leukotoxins, HlgAB and LukED, target the Duffy antigen receptor for chemokines on erythrocytes, resulting in lysis and iron release.


Alpha subunit and human chorionic gonadotropin in normal pregnancy and gestational trophoblastic disease.
The reported incidence of gestational trophoblastic disease is an order of magnitude higher in Nigeria than in the United States. Sera from a total of 283 pregnant black patients, 138 United States and 148 Nigerian pregnant patients, were analyzed for their serum levels of alpha subunit and human chorionic gonadotropin (hCG). The patterns of hCG secretion were similar in the two populations during normal pregnancy. However, the level of alpha subunit was persistently higher in Nigerian women than in comparable pregnant United States patients. A statistically significantly higher alpha subunit level in the Nigerian patients was found only in the ten- to 13-week gestational period (P less than .005). The higher level of alpha subunit in pregnancy in Nigerian women may signal a population of trophoblastic cells which may be at higher risk for malignancy development in the Nigerian woman.


Anti-Inflammatory Properties of Longifuran A, a New Benzofuran from the Stems of Amomum longiligulare.
In this study, the following compounds were isolated from the dichloromethane fraction of the stems of Amomum longiligulare and then characterized: a new benzofuran, namely, longifuran A (1); five other phenolic compounds, namely, 4-methoxycinnamic acid (2), 2,5-dimethoxyphenol (3), eudesmic acid (4), 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (5), and 4,4'-dihydroxychalcone (6); and two triterpenoids, namely, 24-methylcycloartan-3β-ol (7) and 24-methylencycloartan-3β-ol (8). They were evaluated in terms of their inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophages. Results indicated that 1 and 5 exhibited promising inhibitory activities against NO generation with IC50 of 10.47±1.02 μM and 8.51±1.14 μM, respectively. Enzymatic assays demonstrated that they remarkably suppressed the secretion of two pro-inflammatory cytokines (i. e., IL-6 and TNF-α). They also dose-dependently inhibited the expression of inducible nitric oxide synthase and cyclooxygenase-2, two important enzymes modulating inflammation. Therefore, 1 and 5 could be targets for the development of new anti-inflammatory therapeutics.


Exposure characteristics of phthalate metabolites among the Zunyi cohort of pregnant women in Southwest China.
Reported evidence has increasingly indicated that exposure to phthalates can cause adverse pregnancy outcomes. However, phthalate exposure levels among pregnant women remains unclear. We aimed to evaluate the concentrations and predictors of phthalate metabolites in urine samples of the ongoing Zunyi cohort of pregnant women from Southwest China. The urine samples were collected from 1003 pregnant women during their third trimester of pregnancy. The concentrations of nine phthalate metabolites in urine samples were then determined. Data on socio-demographic profiles of the participants, lifestyle during pregnancy, parity, and sampling season were collected using questionnaires. The detectable rate of phthalate metabolites ranged from 76 to 100%. On average, mono-butyl phthalate exhibited the highest median concentration (62.45 μg/L), while mono-benzyl phthalate exhibited the lowest median concentration (0.04 μg/L). Urine concentrations of phthalate metabolites were significantly higher in older, multiparous, higher body mass index, higher income, and passive smoking during pregnancy participants. The levels of low-molecular-weight phthalate metabolites were highest during the summer. The findings indicate the health of pregnant women and fetuses in Zunyi may be generally harmed by the high exposure of phthalate metabolites, especially by mono-n-butyl phthalate. In addition, phthalate metabolites present a demographic and seasonal differential distribution among the study population. Targeted measures to reduce phthalate exposure for high-risk pregnant women and during high-exposure seasons may have potential benefits for maternal and fetal health protection.


Carbon Nanotubes Exposure Risk Assessment: From Toxicology to Epidemiologic Studies (Overview of the Current Problem).
Nanoscale size and fiber like structure of carbon nanotubes (CNTs) may determine high reactivity and penetration, as well as the pathogenicity of asbestos and other mineral fibers. Despite many in vitro and in vivo studies, the absence of full-scale data on CNT effects on human health clearly point out the necessity for epidemiological studies. Currently, several projects are initiated worldwide on studying health risks associated with the inhalation of industrial CNTs, including NIOSH-promoted research (United States), the European CANTES study, and the Russian CNT-ERA project. Studies comprising several successive steps, such as CNT exposure assessment in occupational settings, toxicological evaluation, and epidemiological observations, are critical for determining material safety and use criteria.


Induction of tyrosine hydroxylase in the locus coeruleus of transgenic mice in response to stress or nicotine treatment: lack of activation of tyrosine hydroxylase promoter activity.
Prolonged stress or chronic nicotine administration leads to induction of tyrosine hydroxylase (TH) in adrenal medulla and locus coeruleus (LC) of the rat. In this study we use mice that express a transgene encoding 4.5 kb of TH gene 5'-flanking region fused upstream of the reporter gene, human alkaline phosphatase (hAP) to test whether TH gene promoter activity is stimulated by immobilization stress, cold exposure or nicotine administration in adrenal medulla and LC. TH-hAP transgene expression is increased in response to all three stimuli in the adrenal medulla. In contrast, TH-hAP expression does not increase in response to either immobilization stress or nicotine administration in the LC and only a small induction of LC TH-hAP mRNA is observed in response to cold exposure. TH mRNA is induced 2-3 fold and TH activity is increased significantly by all three stimuli in both the adrenal and LC. These results support the hypothesis that TH expression is induced by stress or nicotine treatment in both the adrenal medulla and LC of the mouse. The induction in the adrenal is dependent primarily on transcriptional mechanisms, whereas that in the LC is apparently dependent primarily on post-transcriptional mechanisms.


The effects of intrinsic foot muscle strengthening on functional mobility in older adults: A systematic review.
Weakness and disuse of intrinsic foot muscles contributes to dysfunction in foot and toe alignment and sensory input, which may lead to instability and falls in older adults. The aim of this systematic review was to report the effects of intrinsic foot muscle strengthening (IFMS) interventions on functional mobility in adults aged ≥65 years. A systematic review was performed with searches from December 2019-February 2021 using MEDLINE, CINAHL, SPORTDiscus, Rehab and Sports Medicine Source, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. Additional sources were sought using reference scanning. Eligible sources analyzed adults aged ≥65 years (n = 1674) who were ambulatory, used a functional mobility outcome measure, and contained foot and ankle interventions that included IFMS. Literature studies regarding neurological, vestibular, cognitive, amputation, or post-surgical conditions were excluded. Studies that did not specify intrinsic foot muscle involvement were excluded. Two authors extracted relevant studies and appraised them using the Physiotherapy Evidence Database (PEDro) scale. A total of 1420 articles were screened for relevance, and 16 were extracted. Five additional sources were obtained through reference scanning. Nine articles were eligible for review. PEDro scores ranged from 3 to 7 (out of 10), indicating "fair" quality of evidence. Heterogeneity of methods and data did not allow for statistical comparison. Themes extracted from sources were types of intrinsic foot strengthening interventions and parameters; outcomes on falls, balance, functional mobility; and subjective reports regarding functional mobility. Evidence reviewed was of fair quality. IFMS interventions contributed to improvements in strength, balance, mobility, and possibly reduced fall risk. There was little effect on gait. Subjective reports indicate a possible mechanism for improved mobility may be from increased proprioception and sensation.


Sex Determination in Japanese Quails (Coturnix japonica) Using Geometric Morphometrics of the Skull.
The study investigated whether there is a morphological difference between the shape of the female and male quail's skulls. For this purpose, 18 female and 21 male quails were used. After the skulls were obtained, their photographs were taken, and geometric analysis was performed. Dorsal (14 landmarks), caudal (8 landmarks), and ventral (13 landmarks) images of skulls were evaluated. As a result of the Principal Component Analysis (PCA), 28 principal components (PCs) were obtained for dorsal view, 16 PCs for caudal view, and 26 PCs for ventral view. PC1 (41.206%) for the caudal aspect explained the highest shape variation in terms of sex. It was seen that PC1 for dorsal view explained 33.046% and PC1 for ventral view explained 34.495% shape variation. For the dorsal view, the orbital pit of males was found to be deeper than females. The foramen magnum was narrower in female skulls. The lateral borders of the neurocranium were more pointed upwards in males. On ventral view, it was seen that male individuals had a wider skull in shape. Geometrically, it was determined that the male and female distinction was the best in the dorsal view. According to the dorsal view, only one male individual was found to be in the female group, and all other male individuals were completely separated from the females. After the dorsal view, the best distinction was seen ventrally. In the caudal examination, sexual discrimination was not fully seen. In this study, shape differences in quail's skulls were examined between sexes, and shape differences were revealed geometrically. In addition to traditional morphometry studies, it is thought that geometric analysis studies will add a useful perspective to the literature.


Genetic susceptibility analysis of FGF5 polymorphism to preeclampsia in Chinese Han population.
Fibroblast growth factor 5 (FGF5), which is a well-established causative factor for blood pressure, has been identified as a susceptibility gene for preeclampsia (PE) in European and Central Asian women. Here, we examined whether polymorphism rs16998073 in FGF5 confer a significant risk to PE in Chinese Han population by case-control association analysis. FGF5 rs16998073 was genotyped by Sanger sequencing in women with preeclampsia (n = 187) and healthy controls (n = 229) of Han Chinese. We found the frequency of rs16998073T allele was significantly higher in PE patients than that in controls. Next, we utilized dual-luciferase reporter assays and electrophoretic mobility shift assay (EMSA) reactions to investigate whether rs16998073 different alleles could affect the transcriptional activity of FGF5. The dual luciferase reporter assay showed that T allele increased the transcriptional efficiency by 1.5-fold compared with the G allele. Similarly, EMSA revealed that the T allele had a strong transcription factor binding strength compared with the G allele. We then examined the mRNA and protein expression levels of FGF5 in placental tissues by real-time PCR and Western blot assays. We found FGF5 were significantly upregulated in placental tissues from PE patients or PE mouse model than their corresponding controls. In addition, in vitro cell experiments confirmed that FGF5 could promote cell apoptosis of HTR8/SVneo and inhibit cell invasion. Taken together, our data provide evidence implicating rs16998073 of FGF5 as a functional genetic risk variant for PE disease and FGF5 might participate in development of PE disease.


Hypothalamic dopamine-beta-hydroxylase activity: fluctuations with time of day and their modifications by intracranial surgery, adrenalectomy, and pinealectomy.
Hypothalamic and plasma dopamine-beta-hydroxylase [DBH, EC 22.214.171.124] activites were measured by a coupled radioenzymatic method. Animals representing five experimental groups [intact controls, adrenalectomized, pinealectomized, adrenalectomized pinealectomized, doubly sham-operated] were killed and sampled at 8 times through the 24-hr daily cycle, 15 days postoperation, and at 50-52 days of age. Hypothalamic DBH in intact control animals had statistically significant fluctuations in relation to time of day. These changes were lost or dampened in groups that had had intracranial surgery and were characteristically shifted by adrenalectomy, either alone or with pinealectomy. Plasma DBH fluctuations in the same animals resembled those in hypothalamus in some features (e.g., peak near mid-dark; shift in daily maxima and minima after adrenalectomy) and differed in others [e.g., no effect of intracranial surgery or of sham operation; adrenalectomized pinealectomized animals resembled the solely pinealectomized]. Although temporal patterns in hypothalamic DBH activity thus differed in the experimental animal groups, the daily means of hypothalamic DBH activity were similar.


FgEaf6 regulates virulence, asexual/sexual development and conidial septation in Fusarium graminearum.
Fusarium graminearum is a destructive fungal pathogen and a major cause of Fusarium head blight (FHB) which results in severe grain yield losses and quality reduction. Additionally, the pathogen produces mycotoxins during plant infection, which are harmful to the health of humans and livestock. As it is well known that lysine acetyltransferase complexes play important roles in pathogenesis, the roles of the Eaf6 homolog-containing complex have not been reported in fungal pathogen. In this study, a Eaf6 homolog FgEaf6 was identified in F. graminearum. To investigate the functions of FgEaf6, the gene was deleted using the split-marker method. ΔFgEaf6 mutant exhibited manifold defects in hyphal growth, conidial septation, asexual and sexual reproduction. Moreover, the virulence of the ΔFgEaf6 mutant was drastically reduced in both wheat heads and wheat coleoptiles. However, the FgEaf6 gene deletion did not impact DON production. An FgEaf6-gfp fusion localized to the nucleus and a conserved coiled-coil (C-C) domain was predicted in the sequence. Mutants with deletions in the C-C domain displayed similar defects during development and virulence as observed in the ΔFgEaf6 mutant. Moreover, the truncated gene was cytoplasm localized. In conclusion, the FgEaf6 encodes a nuclear protein, which plays key regulatory roles in hyphal growth, conidial septation, asexual/sexual reproduction, and the virulence of F. graminearum. The C-C is an indispensable domain in the gene. This is the first report on Eaf6 homolog functioning in virulence of fungal pathogen.


Survival of refrigerated Tatochila butterflies (Lepidoptera: Pieridae) as an indicator of male nutrient investment in reproduction.
Tatochila butterflies show prolonged survival in cold (2° C) storage. Mating significantly reduces survival in males, suggesting that nutrients may be directed into spermatophores or maintenance under storage conditions; this provides a potential index of male nutrient investment in reproduction.


Autoradiographic detection of 6-thioguanine-resistant lymphocytes of mice. A novel system in somatic mutagenesis testing.
After treatment of mice with ethylnitrosourea in vivo, induction of 6-thioguanine-resistant splenic lymphocytes was measured in vitro. The lymphocytes were mitogen-stimulated in presence of thioguanine. After a culture period of 30 h, TG resistance was determined by the ability of cells to incorporate [3H]thymidine. The results suggest that at this selection condition the majority of resistant cells stem from somatic mutations. Thus, the system is potentially useful as a screening assay for somatic mutagenesis testing. The problem of misleading results due to the presence of phenocopies was investigated by treatment in vitro with UV radiation or ethylnitrosourea.


Electrospray ionization mass spectrometry analysis of polyisoprenoid alcohols via Li+ cationization.
Direct analysis of polyisoprenoids by electrospray ionization mass spectrometry (ESI-MS) often produces poor results requiring off-line time and sample-consuming derivatization techniques. We describe a simple ESI-MS approach for the direct analysis of polyisoprenoids using several dolichols and polyprenols with different chain sizes as proof-of-principle cases. Lithium iodide is used to promote cationization by intense formation of [M+Li]+ adducts. Thus, detection of polyisoprenoids with mass determination can be performed with high sensitivity (limit of detection [LOD] approximately 100 rhoM), whereas characteristic collision-induced dissociations observed for both dolichols and polyprenols permit investigation of their structure. Using ESI(Li+)-MS and ESI(Li+)-MS/MS analysis, we screened for polyprenol products of an octaprenyl pyrophosphate synthase of Plasmodium falciparum and dolichols in a complex mixture of compounds produced by Leishmania amazonensis and P. falciparum.


PREPARATIVE ISOLATION AND PURIFICATION OF FOUR FLAVONOIDS FROM DAPHNE GENKWA SIEB. ET ZUCC. BY HIGH-SPEED COUNTERCURRENT CHROMATOGRAPHY.
Four flavonoids including luteolin, apigenin, 3'-hydroxygenkwanin and genkwanin were isolated and purified from Daphne genkwa Sieb. et Zucc. by high-speed countercurrent chromatography (HSCCC). Preparative HSCCC with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (5:7:5:5, v/v) was successfully performed by increasing the flow rate of the mobile phase from 1.2 to 2.0 mL/min after 260 min. In a one-step operation, 150 mg of the extracts of D. genkwa was separated to yield 8 mg of luteolin, 25.8 mg of apigenin, 23.6 mg of 3'-hydroxygenkwanin and 35.3 mg genkwanin with the purities of 91.2, 97.4, 94.3 and 95.8%, respectively, analyzed by HPLC using area normalization method. The chemical structures of the four compounds were identified by HPLC, ESI-MS, and (1)H NMR.


Titania-based molecularly imprinted polymer for sulfonic acid dyes prepared by sol-gel method.
A novel titania-based molecularly imprinted polymer (MIP) was synthesized through sol-gel process with sunset yellow (Sun) as template, without use of functional monomer. MIP was used as a solid-phase extraction material for the isolation and enrichment of sulfonic acid dyes in beverages. The results showed that MIP exhibited better selectivity, higher recovery and adsorption capacity for the sulfonic acid dyes compared to the non-imprinted polymer (NIP). MIP presented highest extraction selectivity to Sun when pH less than or equal to 3. The adsorption capacity was 485.9 mg g(-1), which was larger than that of NIP (384.7 mg g(-1)). The better clean-up ability demonstrated the capability of MIP for the isolation and enrichment of sulfonic acid dyes in complicated food samples. The mean recoveries for the sulfonic acid dyes on MIP were from 81.9% to 97.2% in spiked soft drink.


[Screening for aneuploidy by first trimester nuchal translucency measurement: results from a prospective trial including 1980 cases in a single center in Switzerland].
The purpose of this study was to evaluate the efficiency of first trimester screening for chromosomal abnormalities using the sonographically determined thickness of nuchal translucency (NT) combined with maternal age. Risk screening was offered to all patients with a fetal crown rump length (CRL) between 45 and 84 mm after extensive counselling. For the risk assessment the software provided by the Fetal Medicine Foundation was used. In accordance with the recommendation of the Swiss Working Group on First Trimester Screening a cut-off risk of 1 : 400 was chosen. A total of 1980 consecutive pregnancies participating in the risk screening programme with due dates prior to May 1, 2001 were included. Mean maternal age was 30.1 yrs and 522 (26.4 %) patients were 35 yrs or older. A positive risk screening result was obtained in a total of 219 (11.1 %) pregnancies including 33 of the 37 (1.9 %) cases with unbalanced chromosomal abnormalities. The detection rate for unbalanced chromosome abnormalities in general (89.2 %) as well as the one for trisomy 21 (93.3 %) in particular are very high with a moderate false-positive rate (9.6 %) in this series. As a comparison in the series presented here, traditional "maternal age screening" (cut-off age 35 yrs) would have yielded detection rates of 64.9 % for all unbalanced chromosome abnormalities and 73.3 % for trisomy 21 at a false-positive rate of 25.0 %. Reducing the false-positive rate by raising the cut-off age to 38 yrs would yield detection rates of 40.5 % for all unbalanced chromosome abnormalities and 46.7 % for trisomy 21 at a false-positive rate of 8.9 %. The number of invasive procedures performed to detect one unbalanced chromosome count may be calculated as 21.75 using the cut-off age of 35 yrs as compared to 6.4 using NT measurement and maternal age. The outcome of this ongoing study is in good accordance with the earlier observation that the main benefit of the addition of first trimester NT measurements to the risk screening protocol is a very high detection rate at a moderate false-positive rate.


Does the roller pump adjustment in cardiopulmonary bypass settings influence hemolysis?
Roller pumps are widely used in procedures involving cardiopulmonary bypass (CPB) due to their ease of operation and maintenance, safety, and cost. Several studies in the literature have compared the use of roller pumps with centrifugal pumps, but the influence of the roller pump adjustment on hemolysis has been poorly explored. Measurements of hemolysis rates were carried out in 86 patients. The pump was adjusted by the dynamic calibration method, which was performed by an auxiliary device, and the patients were grouped according to the pump calibration: Group 1 (n = 20) 75 mmHg; Group 2 (n = 24) 150 mmHg; Group 3 (n = 22) 300 mmHg and Group 4 (n = 21) 450 mmHg. The hemolysis rates were measured at 4 different times during CPB (T0: before the surgical procedure; T1: 5 minutes after the start of CPB; T2: 30 minutes of CPB; and T3: 5 minutes after the CPB procedure). Hemolysis rates were calculated between the time intervals T0-T1, T1-T2, and T0-T3. No difference in hemolysis rates was observed between the groups (p>0.31). During the first 5 minutes of CPB, hemolysis represented 35.5% of the total hemolysis and no significant difference was found between groups (p>0.60). Calibration of roller pumps by the dynamic method did not influence the hemolysis rates. Additionally, the hemolysis during the first 5 minutes of CPB accounted for ~1/3 of the total hemolysis.


Safe laparoscopic surgery in the elderly.
The elderly are more prone to complications of surgery because of comorbidity, and they may benefit most from a minimally invasive approach. This study was intended to evaluate the safety of the use of a laparoscopic approach for emergency and elective surgery in elderly patients. From January 2000 to June 2001, all patients over 75 years of age who underwent a procedure that began laparoscopically were included. Physiologic and operative scores according to the POSSUM scoring system were recorded. These were then used to calculate predicted morbidity and mortality by both the POSSUM and P-POSSUM systems. Predicted outcomes were compared with actual outcomes. One hundred sixty-two patients with a mean age of 80 years were included; 52% were emergency cases. The overall morbidity was 14.5% and the mortality rate was 1.8%. Fourteen procedures (8.4%), all emergencies, were converted. Both mortality and morbidity rates were lower than the predicted values (P = 0.001 and P = 0.0001, respectively). A laparoscopic approach can be used safely in an elderly population undergoing surgery in a daily practice for miscellaneous conditions, whether elective or emergency operations.


Mono- and dinuclear zinc complexes bearing identical bis(thiosemicarbazone) ligand that exhibit alkaline phosphatase-like catalytic reactivity.
Mono- and dinuclear zinc(II) complexes bearing bis(thiosemicarbazone) (bTSC) ligand were employed in the cleavage of phosphoester bonds. Comparative kinetic studies combined with theory suggested that the P-O bond cleavage is much accelerated by dinuclear zinc(II) complex in the presence of base. Based on the DFT-optimized structures of the proposed intermediates, it is plausible that (1) the removal of sulfur atoms of bTSC ligand from the zinc center provides two vacant sites for the binding of water (or hydroxide ion) and phosphoester and (2) the H-bonding between water (or hydroxide ion) and phosphoester, through several water molecules, may also assist the P-O bond cleavage and facilitate the nucleophilic attack. The kinetic and catalytic studies on the hydrolysis of phosphoester by dinuclear zinc complex showed a much-enhanced reactivity under basic reaction conditions, reaching over 95% conversion yield within 4 h. The currently presented compounds are arguably one of the faster synthetic Zn-based model performing phosphatase-like activity presented so far.


Degradation of Abies veitchii wave-regeneration on Mt. Misen in Ohmine Mountains: effects of sika deer population.
How has the degradation of Abies veitchii wave-regeneration occurred under the sika deer (Cervus nippon) pressure? We conducted tree census and ground vegetation survey in a 1 ha plot in Mt. Misen (Nara prefecture, Japan). We found 15 tree species (over 50 cm in height). Abies accounted for 60.0 % of all living trees, and 46.9 % of Abies were damaged (herbivory, bark stripping and/or fraying) by deer. Spatial distribution of Abies trees showed Abies-wave, although there were few saplings in the dieback zone. Estimated deer population density in 2009 was 57.3 head/km(2). Number of living Abies and standing dead conifer trees, and ground vegetation cover for each quadrat (5 × 5 m) were used to assign the quadrats into 6 clusters. The hierarchical clustering-approach revealed that living Abies distributed mainly on the moss and/or Carex fernaldiana dominated quadrats, but did not on the Dennstaedtia scabra, or Brachypodium sylvaticum dominated quadrats. While standing dead conifer trees distributed mainly on the Carex dominated quadrats, they hardly occur on the moss, the Dennstaedtia or the Brachypodium dominated quadrats. Regeneration of Abies tree and thus the wave-regeneration is hindered for now owing to deer herbivory and bark-stripping. The ground vegetation under the dieback zone has changed from the moss and/or the Carex dominated one to the Carex, the Dennstaedtia or the Brachypodium covered vegetation with the canopy remained open and without Abies regeneration.


Plasma retinol-binding protein response to vitamin A administration in infants susceptible to bronchopulmonary dysplasia.
We hypothesized that changes in plasma retinol-binding protein (RBP) concentration in response to vitamin A administration might be useful for evaluating vitamin A status of very low birth weight infants susceptible to bronchopulmonary dysplasia. We prospectively studied 24 consecutively admitted neonates (birth weight less than 1350 gm, gestational age less than 31 weeks, ventilator dependent for greater than 24 hours after birth), who were eligible to receive 2000 IU supplemental vitamin A by intramuscular injection on postnatal day 1 and on alternate days thereafter for 28 days. In addition to serial assessment of vitamin A status, we measured plasma RBP just before and 1, 3, and 6 hours after an intramuscular injection of vitamin A (2000 IU/kg retinyl palmitate) on days 1 and 28. The percent increase in plasma RBP (delta-RBP) was high (mean +/- SD: 61 +/- 37%) and plasma vitamin A and RBP values were low on day 1, indicative of vitamin A deficiency. Supplemental vitamin A improved vitamin A status of all infants as shown by low delta-RBP (mean +/- SD: 8 +/- 9%) and normal plasma vitamin A and RBP values on day 28. Bronchopulmonary dysplasia was diagnosed in 12 of 24 infants. Infants with bronchopulmonary dysplasia had a higher mean (+/- SD) delta-RBP on day 28 than those without bronchopulmonary dysplasia (13 +/- 10% vs 3 +/- 3%, p less than 0.01), indicative of persistence of low vitamin A status in infants with lung disease despite supplementation. We conclude that the plasma RBP response to vitamin A is a useful indicator of vitamin A status in very low birth weight infants. Although vitamin A supplementation at the dosage used in this study normalizes conventional plasma indexes of vitamin A in very low birth weight infants, the plasma RBP response to vitamin A may continue to reflect persistence of low vitamin A status in the more immature infants with significant lung disease. We suggest that the plasma RBP response to vitamin A may be a useful functional test in such infants.


Growth parameters in HIV-vertically-infected adolescents on antiretroviral therapy in Rio de Janeiro, Brazil.
Growth failure in HIV-infected children is an important factor in either initiating or changing antiretroviral therapy (ART). This study assesses the impact of HIV infection on growth parameters of adolescents who acquired HIV vertically. This retrospective, longitudinal study involved adolescents aged 10-20 years with vertically-acquired HIV infection who were followed up in one of the three main referral centres for paediatric HIV/AIDS in Rio de Janeiro, Brazil. Length, weight and variables related to demographic, clinical and laboratory issues were analysed. 108 subjects were enrolled. Median age was 12.7 years, median duration of follow-up was 97.2 months and 61 (56.5%) were female. The difference between the baseline and final weight Z-scores was -0.31 (p=0.02). Patients with final weight Z-scores < or = -2 used more ART regimens (average 4.13) than those with Z-scores > -2 (average 2.90, p<0.01) and also had a lower final CD4+ cell percentage--average 19% vs 24% (p<0.01), respectively. The difference between baseline and final-height Z-scores was -0.27 (p<0.01). Several factors were associated with a final-height Z-score < or = -2: clinical stage C during follow-up (RR 1.60, 95% CI 1.11-2.31), chronic diarrhoea during follow-up (RR 2.02, 95% CI 1.04-3.90), HAART use (RR 1.41, 95% CI 1.16-1.71), number of ART regimens (p<0.01) and final CD4+ cell percentage (p<0.01). In multivariate analysis, presentation in clinical stage C during follow-up was the only significant variable (OR 4.04, 95% CI 1.23-13.28). Even on HAART, HIV-infected adolescents have lower growth parameters than the normal population and this is associated with a worse prognosis.


Synthesis and biological evaluation of chromanone-based derivatives as potential anti-neuroinflammatory agents.
As a privileged scaffold, chromanone has been extensively introduced in the design of drug leads with diverse pharmacological features, particularly in the area of inflammatory diseases. Herein, the preparation of chromanone-based derivatives (4a-4i) was smoothly achieved, and their structures were characterized using 1H NMR, 13C NMR, and ESI-HRMS spectroscopy techniques. Out of them, analogue 4e exhibited the most potent inhibitory capacity against the NO release and iNOS expression, without apparent cytotoxicity. Our observations showed that 4e could dramatically prevent the translocation of NF-κB from the cytoplasm to nucleus, and decrease the production of proinflammatory cytokines TNF-α, IL-6 and IL-1β in LPS-induced BV-2 cells. Mechanistically, 4e significantly deactivated NF-κB by disturbing TLR4-mediated TAK1/NF-κB and PI3K/Akt signaling cascades. Consistent with the in vitro study, 4e could effectively mitigate the inflammation response of hippocampal tissue in LPS-induced mouse model by inhibiting microglial activation. Collectively, these results revealed 4e as a prospective neuroprotective candidate for the therapy of neuroinflammation-related disorders.


Testicular migration: remodeling of connective tissue and muscle cells in human gubernaculum testis.
We present the main morphological modifications in the human gubernaculum during testicular migration in humans. We obtained 12 gubernacula from fresh, macroscopically normal human fetuses at 15 to 29 weeks of gestation. Collagen was evidenced using trichrome and Sirius red staining procedures, while Weigert's resorcinol-fuchsin and anti-human elastin antibody were used to reveal elastic system fibers. Smooth muscle cells were detected by anti-human smooth muscle alpha-actin antibody. When the testes were still located in the abdomen at 15 to 16 weeks of gestation, collagen fibers were sparse and embedded in a loose extracellular matrix. The amount of fibers then gradually increased with age and at 28 weeks of gestation the gubernaculum was mostly collagenous in composition. Elastic fibers had a similar growth pattern, although they were located mainly at the distal end of the gubernaculum. Fibroblasts largely predominated over other cell types and decreased in number with gestational age, whereas smooth muscle cells were restricted to the walls of blood vessels. Striated muscle cells were detected at the scrotal end of the gubernaculum, where they were disposed as isolated and scattered bundles running in various directions. Like fibroblasts, their number also decreased with age. During testicular migration gubernacular connective tissue undergoes extensive remodeling and ultimately becomes an essentially fibrous structure rich in collagen and elastic fibers. Such changes should decrease the size of the gubernaculum and, thus, contribute to other forces that cause the testes to move toward the scrotum. In fact, because of the lack of smooth muscle cells, and the amount and organization of striated muscle cells, active contraction of the gubernaculum is less likely to be an important factor in testicular descent.


Retraction: Smartphone interventions effect in pediatric subjects on the day of surgery: a meta-analysis.
[This retracts the article DOI: 10.3389/fsurg.2021.759958.].


The flow of gene expression.
Gene expression is a highly interconnected multistep process. A recent meeting in Iguazu Falls, Argentina, highlighted the need to uncover both the molecular details of each single step as well as the mechanisms of coordination among processes in order to fully understand the expression of genes.


Trafficking and function of the tetraspanin CD63.
Tetraspanins comprise a large superfamily of cell surface-associated membrane proteins characterized by four transmembrane domains. They participate in a variety of cellular processes, like cell activation, adhesion, differentiation and tumour invasion. At the cell surface, tetraspanins form networks with a wide diversity of proteins called tetraspanin-enriched microdomains (TEMs). CD63 was the first characterized tetraspanin. In addition to its presence in TEMs, CD63 is also abundantly present in late endosomes and lysosomes. CD63 at the cell surface is endocytosed via a clathrin-dependent pathway, although recent studies suggest the involvement of other pathways as well and we here present evidence for a role of caveolae in CD63 endocytosis. In late endosomes, CD63 is enriched on the intraluminal vesicles, which by specialized cells are secreted as exosomes through fusion of endosomes with the plasma membrane. The complex localization pattern of CD63 suggests that its intracellular trafficking and distribution must be tightly regulated. In this review we discuss the latest insights in CD63 trafficking and its emerging function as a transport regulator of its interaction partners. Finally, the involvement of CD63 in cancer will be discussed.


Understanding the relationship between cancer associated cachexia and hypoxia-inducible factor-1.
Cancer-associated cachexia (CAC) is a multifactorial disorder characterized by an unrestricted loss of body weight as a result of muscle and adipose tissue atrophy. Cachexia is influenced by several factors, including decreased metabolic activity and food intake, an imbalance between energy uptake and expenditure, excessive catabolism, and inflammation. Cachexia is highly associated with all types of cancers responsible for more than half of cancer-related mortalities worldwide. In healthy individuals, adipose tissue significantly regulates energy balance and glucose homeostasis. However, in metastatic cancer patients, CAC occurs mainly because of an imbalance between muscle protein synthesis and degradation which are organized by certain extracellular ligands and associated signaling pathways. Under hypoxic conditions, hypoxia-inducible factor-1 (HIF-1α) accumulated and translocated to the nucleus and activate numerous genes involved in cell survival, invasion, angiogenesis, metastasis, metabolic reprogramming, and cancer stemness. On the other hand, the ubiquitination proteasome pathway is inhibited during low O2 levels which promote muscle wasting in cancer patients. Therefore, understanding the mechanism of the HIF-1 pathway and its metabolic adaptation to biomolecules is important for developing a novel therapeutic method for cancer and cachexia therapy. Even though many HIF inhibitors are already in a clinical trial, their mechanism of action remains unknown. With this background, this review summarizes the basic concepts of cachexia, the role of inflammatory cytokines, pathways connected with cachexia with special reference to the HIF-1 pathway and its regulation, metabolic changes, and inhibitors of HIFs.


Recovery to Preinterventional Functioning, Return-to-Work, and Life Satisfaction After Treatment of Unruptured Aneurysms.
The eventual goal of preventive treatment of unruptured intracranial aneurysms is to increase the number of life years with high life satisfaction. Insight in the time with reduced functioning, working capacity, and life satisfaction after aneurysm treatment is pivotal to balance the pros and cons of preventive aneurysm occlusion. We sent a questionnaire on time-to-recovery to preintervention functioning and return-to-work and life satisfaction to patients treated for an unruptured aneurysm between 2000 and 2013. Changes in life satisfaction before treatment, during recovery, and at follow-up were assessed with Wilcoxon signed-rank tests. The questionnaire was sent to 159 patients of whom 110 (69%) responded. The mean follow-up time after aneurysm treatment was 6 years (SD 4). Fifty-four patients had endovascular and 56 had microsurgical occlusion. Complete recovery to preintervention functioning was reported by 81% (95% confidence interval [CI], 74-88) of patients, with a median time-to-recovery of 3 months (range 0-48). Complete work recovery was reported by 78% (95% CI, 66-87) of patients. The proportion of patients with high life satisfaction reduced from 76% (95% CI, 67-84) before treatment to 52% (95% CI, 43-61) during the period of recovery (P<0.01) and restored largely at long-term follow-up (67% [95% CI, 59-76], P=0.08). Life satisfaction is significantly reduced during the period of recovery after treatment of unruptured aneurysms. In the long-term, ≈1 out of 5 patients reports incomplete recovery. These treatment effects should be kept in mind when considering preventive aneurysm treatment. Prospective studies are needed to better compare these losses in patients treated for unruptured aneurysms with those who had subarachnoid hemorrhage.


Probiotics are effective at preventing Clostridium difficile-associated diarrhea: a systematic review and meta-analysis.
Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea. CDI has increased in incidence and severity over the past decade, and is a growing worldwide health problem associated with substantial health care costs and significant morbidity and mortality. This meta-analysis examines the impact of probiotics on the incidence of Clostridium difficile-associated diarrhea (CDAD) among children and adults, in both hospital and outpatient settings. A comprehensive literature search of all published randomized control trials (RCTs) assessing the use of probiotics in the prevention of CDAD in patients receiving antibiotic therapy was conducted, and the incidence of CDAD was analyzed. Twenty-six RCTs involving 7,957 patients were analyzed. Probiotic use significantly reduced the risk of developing CDAD by 60.5% (relative risk [RR] =0.395; 95% confidence interval [CI], 0.294-0.531; P<0.001). Probiotics proved beneficial in both adults and children (59.5% and 65.9% reduction), especially among hospitalized patients. Lactobacillus, Saccharomyces, and a mixture of probiotics were all beneficial in reducing the risk of developing CDAD (63.7%, 58.5%, and 58.2% reduction). Probiotic supplementation is associated with a significant reduction in the risk of developing CDAD in patients receiving antibiotics. Additional studies are required to determine the optimal dose and strain of probiotic.


Total versus subtotal hysterectomy: a survey of gynecologists.
To estimate the attitudes and practice of gynecologists in the Washington, DC, Maryland, and Virginia area regarding total versus subtotal abdominal hysterectomy. A questionnaire with 18 questions on physicians' attitudes and practice regarding total versus subtotal hysterectomy was mailed to 1647 gynecologists in Washington, Maryland, and Virginia. The corrected response rate was 51.2%. Forty-five percent of respondents stated that they always removed the cervix. The most common reason cited was to eliminate the risk of cervical cancer. The most common reason for subtotal hysterectomy was surgical difficulty leading to an intraoperative change of procedure. Only 17.8% of respondents always counseled women regarding the advantages and disadvantages of both total and subtotal hysterectomy; 63% rarely or never did. Nineteen percent always offered women a choice between the procedures; 61% rarely or never did. Eighty-eight percent of respondents felt that the risk of cancer in the cervical stump was small or negligible. Gender of the physicians or year of completion of residency made no significant impact on patients being counseled about both procedures or being offered a choice between the two. Most gynecologists surveyed favor total abdominal hysterectomy over subtotal hysterectomy. Few counsel women regarding the options of total and subtotal hysterectomy or offer a choice between the procedures. Given that there are no convincing data proving the superiority of either procedure over the other, it may be reasonable to discuss the potential advantages and disadvantages of both procedures with women undergoing hysterectomy for benign disease and to offer them a choice.