Facially distributed pattern-evoked potentials in multiple sclerosis.
Among 56 established cases of multiple sclerosis in our clinic from April 1978 to March 1985, optic neuritis was found in 38; 21 cases were bilateral. We studied pattern-evoked potentials detected with 16 electrodes placed on both the scalp and the facial area. Pattern-evoked potentials (PERGs) were obtainable at the facial area in multiple sclerosis patients with optic neuritis, except in long-standing cases. However, a significant reduction of amplitude was found even in cases without optic neuritis. No correlation was found between visual acuity and amplitude or peak latency of PERGs in MS patients.


Uric acid is independent and inversely associated to glomerular filtration rate in young adult Brazilian individuals.
Uric acid, the end-product of human purine metabolism, is associated with hypertension, diabetes and obesity. It has also been independently associated with the onset of chronic kidney disease in several populations. In this study, the association between serum uric acid (SUA) level and estimated glomerular filtration rate (eGFR) was investigated in healthy individuals belonging to two Brazilian birth cohorts. Data from 3541 to 3482 individuals, aged 30 and 22-years old, respectively, was included. eGFR was calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on creatinine measurement. Regression analyses were sex-stratified due to interaction between SUA and sex (p < 0.001) and adjusted for perinatal, cardiometabolic and behavioral variables. We observed an inverse association between eGFR and SUA even after adjustment. In the highest tertile (3rd) of SUA, the eGFR coefficients at 30-years were-0.21 (95%CI -0.24;-0.18) for men and -0.20 (95%CI -0.23; -0.17) for women; at 22-years, were -0.09 (95%CI -0.12;-0.05) for men and -0.13 (95%CI -0.15; -0.10) for women. Higher differences among exponential means (95% CI) of eGFR between the 1st and the 3rd tertile of SUA were seen in older participants, being more pronounced in men. At 22-years, the highest difference was found in women. In young healthy individuals from a low-middle income country, SUA level was inversely associated with eGFR. Gender-related differences in eGFR according tertiles of SUA were higher in men at 30-years and in women at 22-years.


Visualizing a Single-Crystal-to-Single-Crystal [2+2] Photodimerization through its Lattice Dynamics: An Experimental and Theoretical Investigation.
In homogeneous solid-state reactions, the single-crystal nature of the starting material remains unchanged, and the system evolves seamlessly through a series of solid solutions of reactant and product. Among [2+2] photodimerizations of cinnamic acid derivatives in the solid state, those involving salts of the 4-aminocinnamic acid have been recognized to proceed homogeneously in a "single-crystal-to-single-crystal" fashion by X-ray diffraction techniques. Here the bromide salt of this compound class is taken as a model system in a Raman spectroscopy study at low wavelengths, to understand how such a mechanism defines the trend of the crystal lattice vibrations during the reaction. Vibrational mode calculations, based on dispersion corrected DFT simulations of the crystal lattices involved in the transformation, have assisted the interpretation of the experiments. Such an approach has allowed us to clarify the spectral signatures and to establish a correlation between the dynamics of the monomer and dimer systems in a process where chemical progress and crystal structural changes are demonstrated to occur simultaneously.


Combination therapy with anti-T-cell immunoglobulin and mucin-domain containing molecule 3 and radiation improves antitumor efficacy in murine hepatocellular carcinoma.
T-cell immunoglobulin and mucin-domain containing molecule 3 (TIM3) has emerged as a promising immune checkpoint inhibitor target; however, immune checkpoint inhibitor monotherapy does not benefit a substantial percentage of patients. Therefore, this study investigated the antitumor effect of anti-TIM3 therapy combined with radiation in a murine hepatocellular carcinoma (HCC) model. The effect of radiation on TIM3 expression was determined in murine and human HCC cells using western blotting, immunohistochemistry, and flow cytometry. Tumor growth and survival rate were measured to evaluate the antitumor effect of this combination therapy. Tumor immunological parameters were assessed using flow cytometry and histology. TIM3 was upregulated in tumor-infiltrating CD8+ and CD4+ T cells in radiation-treated HCa-1-implanted mice. Combination treatment significantly delayed tumor growth compared with monotherapy (P < 0.01). Overall survival was improved in the combination group compared with that in the anti-TIM3 or radiation monotherapy groups (median survival time: 52 days vs 26 or 38 days, respectively, P < 0.001). The antitumor effect of the combination treatment was associated with increased apoptosis and decreased proliferation of tumor cells and reinvigorated CD8+ T-cell activation. CD8+ T-cell depletion reversed the antitumor efficacy of the combination treatment. These findings suggest that CD8+ T cells play key roles in the therapeutic effect of the combination treatment. Anti-TIM3 and radiation combination therapy significantly improved the antitumor effect in a murine HCC model, as evidenced by inhibited tumor growth and increased overall survival. This approach could be a novel combined immune-radiotherapy strategy for HCC.


How filopodia pull: what we know about the mechanics and dynamics of filopodia.
In recent years, the dynamic, hair-like cell protrusions called filopodia have attracted considerable attention. They have been found in a multitude of different cell types and are often called "sensory organelles," since they seem to sense the mechanical and chemical environment of a cell. Once formed, filopodia can exhibit complex behavior, they can grow and retract, push or pull, and transform into distinct structures. They are often found to make first adhesive contact with the extracellular matrix, pathogens or with adjacent cells, and to subsequently exert pulling forces. Much is known about the cytoskeletal players involved in filopodia formation, but only recently have we started to explore the mechanics of filopodia together with the related cytoskeletal dynamics. This review summarizes current advancements in our understanding of the mechanics and dynamics of filopodia, with a focus on the molecular mechanisms behind filopodial force exertion.


The classification of tymoviruses by cDNA-RNA hybridization and other measures of relatedness.
The relationships of twelve tymoviruses have been assessed by cDNA-RNA hybridization. In addition, the percentage molar nucleotide composition of the genome of the PD strain of Kennedya yellow mosaic virus and the percentage molar amino acid composition of the coat proteins of cacao yellow mosaic, Kennedya yellow mosaic and turnip yellow mosaic (Cardamine strain) viruses were estimated. These as well as published serological comparisons and genome and coat protein composition determinations were used to compute classifications of tymoviruses using various "metrics", and simple numerical methods were used to compare the classifications. Measures of relatedness estimated from cDNA-RNA hybridization and base ratio data correlated significantly with each other, but were less closely correlated with those calculated from amino acid data, and did not correlate with those calculated from serological tests. The serological relationships correlated significantly with estimates of relatedness calculated from amino acid data, but not with those based on hybridization or base ratio data. The differences between these classifications mostly resulted from the anomalous behaviour of eggplant mosaic virus, its particles are serologically close to those of other tymoviruses that naturally infect species of the tobacco family, whereas in cDNA-RNA hybridization tests eggplant mosaic virus is closest to the tymoviruses that infect legumes. Similar but smaller anomalies in the characteristics of other tymoviruses were also found.


Indoor formaldehyde removal by three species of Chlorphytum Comosum under the long-term dynamic fumigation system.
Gaseous formaldehyde removal efficiency and physiological characteristics of leaves were investigated through a dynamic fumigation system. Three different species of potted Chlorophytum Comosum, (Green Chlorophytum Comosum for its green leaves), CC (Combined the leaves of Chlorophytum Comosum with leaves half green and half white) and PC (Purple Chlorophytum Comosum for its purple leaves), were exposed to formaldehyde for 7 days. The results showed formaldehyde removal efficiencies in the daytime were 71.07% ± 0.23, 84.66% ± 0.19, and 46.73% ± 0.15 at 1 ppm for GC, CC, and GC plants, respectively, and were 36.21% ± 0.24, 62.15% ± 0.19, and 34.97% ± 0.11 at night. This might be due to higher plant physiological activities (e.g., photosynthesis, respiration, and transpiration) during the daytime than at night. Ten physiological indicators of leaves were chosen to evaluate the 7-day fumigation process, which were chlorophyll, free protein, relative conductivity, malondialdehyde (MDA), hydrogen peroxide (H2O2), hydroxyl radical, superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and total antioxidant capacity (T-AOC). Eight of these indicators increased, while chlorophyll decreased by 22.16%, 6.95%, and 25.32%, and CAT decreased by 18.9%, 17.8%, and 25.30% for GC, CC, and PC respectively. Among all the increasing physiological indicators, relative conductivity and MDA showed the greatest increase by 279.32% and 155.56% for PC. A 15-day recovery study was also conducted using MDA and T-AOC as indicators. The results showed that all the tested plants could be tolerant up to the 8 ppm of formaldehyde concentration for 7 days under dynamic fumigation and needed 10-15 days for self-recovery.


Hydrogen sulfide as a potent scavenger of toxicant acrolein.
Acrolein (ACR) is a metabolic byproduct in vivo and a ubiquitous environmental toxicant. It is implicated in the initiation and development of many diseases through multiple mechanisms, including the induction of oxidative stress. Currently, our understanding of the body defense mechanism against ACR toxicity is still limited. Given that hydrogen sulfide (H2S) has strong antioxidative actions and it shares several properties of ACR scavenger glutathione (GSH), we, therefore, tested whether H2S could be involved in ACR detoxification. Taking advantage of two cell lines that produced different levels of endogenous H2S, we found that the severity of ACR toxicity was reversely correlated with H2S-producing ability. In further support of the role of H2S, supplementing cells with exogenous H2S increased cell resistance to ACR, whereas inhibition of endogenous H2S sensitized cells to ACR. In vivo experiments showed that inhibition of endogenous H2S with CSE inhibitor markedly increased mouse susceptibility to the toxicity of cyclophosphamide and ACR, as evidenced by the increased mortality and worsened organ injury. Further analysis revealed that H2S directly reacted with ACR. It promoted ACR clearance and prevented ACR-initiated protein carbonylation. Collectively, this study characterized H2S as a presently unrecognized endogenous scavenger of ACR and suggested that H2S can be exploited to prevent and treat ACR-associated diseases.


An accessory tongue in a child: A clinical case.
A 20-month-old male patient presented with a tumor on his tongue. The tumor was detected at birth with an initial size of 5 mm; thereafter, it gradually grew larger. The patient had no symptoms, but he frequently touched the tumor, as he grew older. The authors performed a tumor resection under general anesthesia, and the histopathological diagnosis confirmed that it was an accessory tongue, with the same components as that of a normal tongue. An accessory tongue regularly grows bigger as a patient grows older, resulting in dysphagia and articulation disorder. Younger patients should get accessory tongues surgically resected as soon as they are old enough to receive general anesthesia.


The comparative effects of aminoglycoside antibiotics and muscle relaxants on electrical field stimulation response in rat bladder smooth muscle.
It has been reported that several aminoglycoside antibiotics have a potential of prolonging the action of non-depolarizing muscle relaxants by drug interactions acting pre-synaptically to inhibit acetylcholine release, but antibiotics itself also have a strong effect on relaxing the smooth muscle. In this study, four antibiotics of aminoglycosides such as gentamicin, streptomycin, kanamycin and neomycin were compared with skeletal muscle relaxants baclofen, tubocurarine, pancuronium and succinylcholine, and a smooth muscle relaxant, papaverine. The muscle strips isolated from the rat bladder were stimulated with pulse trains of 40 V in amplitude and 10 s in duration, with pulse duration of 1 ms at the frequency of 1-8 Hz, at 1, 2, 4, 6, 8 Hz respectively. To test the effect of four antibiotics on bladder smooth muscle relaxation, each of them was treated cumulatively from 1 μM to 0.1 mM with an interval of 5 min. Among the four antibiotics, gentamicin and neomycin inhibited the EFS response. The skeletal muscle relaxants (baclofen, tubocurarine, pancuronium and succinylcholine) and inhibitory neurotransmitters (GABA and glycine) did not show any significant effect. However, papaverine, had a significant effect in the relaxation of the smooth muscle. It was suggested that the aminoglycoside antibiotics have inhibitory effect on the bladder smooth muscle.


Visualization of adult stem cells within their niches using the Drosophila germline as a model system.
The germaria of the fruit fly Drosophila melanogaster present an excellent model to study germline stem cell-niche interactions. Two to three adult stem cells are surrounded by a number of somatic cells that form the niche. Here we describe how Drosophilae germaria can be dissected and specifically immuno-stained to allow for identification and analysis of both the adult stem cells and their somatic niche cells.


Transition to synchronization in a Kuramoto model with the first- and second-order interaction terms.
We investigate a Kuramoto model incorporated with the first-order and the second-order interaction terms. We show that the model displays the coexistence of multiattractors and different attractors may be characterized by the phase distributions of oscillators. By investigating the transition diagrams in both forward continuation and backward continuation, we find that the synchronous state with unimodal phase distribution is the most stable one while the state in cluster synchrony with evenly distributed bimodal phase distribution is the least stable one. We also present the phase diagram of the model in the parameter space.


Preparation and characterization of antisera and monoclonal antibodies to serotonergic and dopaminergic ligands.
In an attempt to produce polyclonal antisera and monoclonal antibodies to serotonin, SKF 38393 (D-1 agonist), dopamine, and haloperidol (D-2 antagonist) several procedures for the preparation of immunogenic ligand-protein carrier conjugates were investigated. The Mannich reaction utilizing formaldehyde as the chemical linker was used to prepare serotonin-protein conjugates; antibodies raised to this conjugate reacted specifically to the conjugated serotonin moiety but did not react to native serotonin. Chemical conjugations involving dimethylpimelylimidate or N-carboxymethyl derivatives for the coupling of serotonin, dopamine and SKF 38393 to carrier proteins produced antibodies primarily directed against the 'chemical coupling arm' and very little antibody activity against the ligand itself could be detected. Synthesis of a haloperidol derivative suitable for chemical coupling to a protein carrier via oxobutyric acid produced an immunogen which was capable of eliciting both polyclonal and monoclonal antibodies specific for the hapten. The pitfalls of the various chemical conjugation procedures and the difficulties of producing antibodies to free ligands are discussed.


The effect of hand massage on preoperative anxiety in ambulatory surgery patients.
Anxiety in patients awaiting surgery and diagnostic procedures in an ambulatory department can affect the patient's physiological and psychological well-being and outcome. We conducted a quasi-experimental study at a midwestern US community hospital to determine the effects of hand massage on patient anxiety in the ambulatory surgery setting. We also investigated whether adding the hand massage procedure affected the timing and flow of procedures. The results indicated that hand massage reduces anxiety for patients awaiting ambulatory surgery and outpatient procedures. Participants who received hand massage experienced lower anxiety levels than those who received customary nursing care. In addition, the performance of hand massage did not affect the flow or timing of procedures. Hand massage is an easy procedure for nurses to learn and administer, and it is within the scope of perioperative nursing practice.


The utility assessment of Chinese pregnant women towards the birth of a baby with Down syndrome compared to a procedure-related miscarriage.
This study was performed to investigate the preferences of Chinese pregnant women for Down syndrome-affected birth compared to invasive test-related miscarriage, using the standard gamble approach, and to investigate whether there is a difference in Utility Score between general obstetric patients and those who request prenatal screening. An interviewer-administered survey was conducted on 67 women who presented to the General Obstetric Clinic for booking visits and 69 women who presented to the first-trimester Combined Screening Clinic for fetal Down syndrome in a University Obstetric Unit. Preferences for Down syndrome-affected birth compared to invasive test-related miscarriage were assessed using the standard gamble approach. The differences in Utility Scores for the two outcomes and difference in scores between the two study groups were compared. There was no significant difference in any of the Utility Scores studied between the two study groups. Therefore the summary statistics were performed using the whole study population. The median Utility Score for a Down syndrome-birth was 0.20 (IQR: 0.10-0.40), which was significantly lower than that of 0.55 (IQR: 0.40-0.80) for a procedure-related miscarriage (p < 0.001). Also, the Utility Scores were neither found to be associated with any particular patient demographic characteristics nor their perception of the functional disability of individuals with Down syndrome. The Chinese pregnant women in Hong Kong consider a Down syndrome-affected birth as a much worse health state and life event than a miscarriage. Whether or not to have a screening test appeared to be a result of accessibility and affordability rather than fundamental differences in attitude towards Down syndrome. The findings of the study provide important information on how prenatal screening and diagnosis of fetal chromosomal abnormalities should be offered.


Contextual Factors Influencing Production, Distribution, and Consumption of Nutrient-Rich Foods in Bihar, India: A Qualitative Study of Constraints and Facilitators.
Production-to-consumption linkages are important to improve consumption of nutrient-rich foods to tackle malnutrition. However, understanding specific contextual factors influencing production, distribution, and consumption in rural communities is necessary. To explore household-, farm-, and market-level factors affecting consumption of nutrient-rich foods among producer and nonproducer households in Bihar, India. We conducted focus group discussions (FGDs) and key informant interviews (KIIs) in producer and nonproducer households of Gaya and Nalanda districts in Bihar to examine factors affecting production and consumption of red lentils, green leafy vegetables (GLVs), milk, eggs, and chicken. Through the KIIs, we identified distribution chains and elicited market-level challenges faced by producers, sellers, and consumers. Data were translated, transcribed, and analyzed thematically using NVivo version 9. Findings from 27 FGDs indicate that consumers and producers were aware of the importance of nutrient-rich foods to health and the necessity of prioritizing their consumption in children. Food preferences, social factors, seasons, religions, and livestock epidemics influenced consumption. Among producers, consumption was mainly dependent on own production. Nonproducers perceived that production could help overcome the barrier of affordability and improve consumption. Data from 69 KIIs indicated that markets were unfavorable in terms of profitability for producers, spoilage and losses for market players, issues of accessibility, and availability for consumers. A local context-specific multipronged approach such as understanding sociocultural factors, own production, and local markets influencing consumption needs to be examined further to improve consumption of nutrient-rich foods among agricultural communities in India.


The effect of scaling and root planning on the periodontal condition in hemodialysis patients: A clinical trial study.
Periodontitis is very common in kidney patients undergoing hemodialysis. The two diseases interact with each other so that kidney failure exacerbates periodontal disease and periodontal disease increases the severity of the renal failure. This study aimed to compare the effect of scaling and root planning on the periodontal status of hemodialysis patients and the healthy control group. A clinical trial study of 60 subjects, 30 subjects in the dialysis group with chronic periodontitis, and 30 with chronic periodontitis who were systemically healthy was conducted. After a health education session, gingival pocket depth (PD) measurement, and clinical attachment level (CAL), scaling was performed for both groups. Then, the mentioned indices were measured consequently, at 4 and 8 weeks of treatment. Improvement in both groups was analyzed by Mann-Whitney and paired sample t-test at the significance level of 0.05 by SPSS software. In both groups, the decrease in PD and CAL was steadily observed from the first to the third time and the changes from the first to the second and the first to the third time were significant however it was not significant between the second and third time. Mean PD and CAL in the dialysis group were higher than in the nondialysis group, which was significant (p < 0.001) for the mean PD. The mean improvement of PD and CAL in dialysis patients was 14.31 ± 10.48 and 17.60 ± 7.83%, respectively, and the mean improvement of PD in the nondialysis group was significantly higher than in the dialysis group (p = 0.008). Periodontal treatment (scaling) causes more improvement in periodontal clinical parameters in healthy people with periodontitis than in dialysis patients.


Transposition of an intron in yeast mitochondria requires a protein encoded by that intron.
The optional 1143 bp intron in the yeast mitochondrial 21S rRNA gene (omega +) is nearly quantitatively inserted in genetic crosses into 21S rRNA alleles that lack it (omega -). The intron contains an open reading frame that can encode a protein of 235 amino acids, but no function has been ascribed to this sequence. We previously found an in vivo double-strand break in omega - DNA at or close to the intron insertion site only in zygotes of omega + X omega - crosses that appears with the same kinetics as intron insertion. We now show that mutations in the intron open reading frame that would alter the translation product simultaneously inhibit nonreciprocal omega recombination and the in vivo double-strand break in omega - DNA. These results provide evidence that the open reading frame encodes a protein required for intron transposition and support the role of the double-strand break in the process.


Modern indications for cesarean section.
Total cesarean section rates and rates of various indications for primary cesarean section were reviewed for four yearly periods during the past decade. The time periods studied were chosen to follow the introduction of new obstetric practices and technologic advances in monitoring fetal condition. The total cesarean section rate increased from 6.8% to 17.1% during this time. The most common indication for primary cesarean section was cephalopelvic disproportion, which represented approximately 40% of cases during each study period. Primary cesarean section for fetal distress increased to 28.2% but has decreased over the past 2 years to a present rate of 11.7%. Primary cesarean section for breech presentation increased from 12.3% to 21%. From the perspective of this review a total cesarean section rate of 15% is predicted for the future.


Network meta-analysis of topical haemostatic agents in thyroid surgery.
The objective of this study was to investigate the potential benefit of local haemostatic agents for the prevention of postoperative bleeding after thyroidectomy. A systematic literature search was performed, and RCTs involving adult patients who underwent thyroid surgery using either active (AHA) or passive (PHA) haemostatic agents were included in the review. The main outcome was the rate of cervical haematoma that required reoperation. A Bayesian random-effects model was used for network meta-analysis with minimally informative prior distributions. Thirteen RCTs were included. The rate of cervical haematoma requiring reoperation ranged from 0 to 9·1 per cent, and was not reduced by haemostatic agents: AHA versus control (odds ratio (OR) 1·53, 95 per cent credibility interval 0·21 to 10·77); PHA versus control (OR 2·74, 0·41 to 16·62) and AHA versus PHA (OR 1·77, 0·12 to 25·06). No difference was observed in the time required for drain removal, duration of hospital stay, and the rate of postoperative hypocalcaemia or recurrent nerve palsy. AHA led to a significantly lower total postoperative blood loss and reduced operating time in comparison with both the control and PHA groups. The general use of local haemostatic agents has not been shown to reduce the rate of clinically relevant bleeding.


Encouraging Digital Patient Portal Use in Ambulatory Surgery: A Mixed Method Research of Patients and Health Care Professionals Experiences and Perceptions.
As more complex surgery is performed in 1-day admissions there is a growing demand for appropriate postoperative follow-up. A digital patient portal (DPP) is a promising tool to support this and increase patients' quality of recovery. However, both patients and health care professionals have not fully embraced this eHealth technology. This study investigates the extent to which a patient portal is used in a tertiary ambulatory surgical care unit and assesses usability, applicability and user-friendliness both for the patient and health care worker. Mixed method research design combining qualitative and quantitative methods. Four hundred and fifteen patients undergoing knee arthroscopic surgery or endonasal sinus surgery were included. Quantitative log data from the patient platform, clinical outcome measures and a patient questionnaire were used. Additionally, qualitative data was collected through interviews (with patients, n = 13; involved caregivers and physicians, n = 7) and observations (first introduction to patient with platform and team meetings, n = 15). Forty percent of the included patients effectively used the patient platform (≥1 login). The patients mainly used the platform for gathering information; 62% of the active patients on the platform registered questionnaires initiated from the surgery center (eg, preoperative questionnaire) or diaries (e.g, daily follow-up using the Quality of Recovery Scale). Different barriers and facilitators toward DPP implementation were noted. Attention should be paid to the intrinsic and extrinsic motivation for using the portal and to the added value of the portal for the patient and health care professionals. Patients' perceptions of the DPP were positive and an increase in DPP use was observed during the study due to adjustments (eg, technical adjustments). However, a decline over time was noticed. The role of intrinsic and extrinsic motivation of all included parties needs to be further corroborated.


Analysis of β-catenin association with obesity in African Americans with premalignant and malignant colorectal lesions.
African Americans (AA) are at high risk for Colorectal Cancer (CRC). Studies report a 30-60% increase in CRC risk with physical inactivity, obesity and metabolic syndrome. Activation of the WNT/β-catenin (CTNNB1) signaling pathway plays a critical role in colorectal carcinogenesis. Accumulating evidence also indicates a role of WNT-CTNNB1 signaling in obesity and metabolic diseases. To examine the association between obesity, β-Catenin expression and colonic lesions in African Americans. We reviewed the pathology records of 152 colorectal specimens from 2010 to 2012 (46 CRCs, 74 advanced adenomas and 32 normal colon tissues). Tissue Microarrays (TMA) were constructed from these samples. Immunohistochemistry (IHC) for CTNNB1 (β-Catenin; clone β-Catenin-1) was performed on the constructed TMAs. The IHC results were evaluated by 2 pathologists and the nuclear intensity staining was scored from 0 to 4. BMI, sex, age, location of the lesion and other demographic data were obtained. Positive nuclear staining in normal, advanced adenoma and CRC was 0, 24 and 41%, respectively (P < 0.001). CRC was asso ciated with positive status for nuclear CTNNB1 intensity (adjusted OR: 3.40, 95%CI = 1.42-8.15, P = 0.006 for positive nuclear staining) compared to non-CRC samples (Normal or advanced adenoma). Nuclear staining percentage has a fair diagnostic ability for CRC with an AUC of 0.63 (95%CI = 0.55-0.71). Overweight/obese patients (BMI > 25) did not show a significant difference in (p = 0.3) nuclear CTNNB1 staining (17% positive in normal weight vs. 27% positive in overweight/obese). The association between nuclear intensity and CRC was not different between normal and overweight patients (P for interaction = 0.6). The positive nuclear CTNNB1status in CRC stage III and IV (35% of all CRC) was not different from stage I and II (50% vs. 36%, respectively, P = 0.4). In our study, advanced adenoma and CRC were associated with activation of β-catenin in physically fit, overweight and obese patients. Thus, obesity and WNT/β-Catenin pathway seem to be independent in African American patients. WNT/β-Catenin signaling pathway has a potential to be used as an effector in colon carcinogenic transformation. Whether or not BMI is a modifier of this pathway needs to be investigated further.


Preeclampsia and gestational diabetes mellitus: pre-conception origins?
Preeclampsia (PE) and gestational diabetes mellitus (GDM) are two of the most common medical complications of pregnancy, with risks for both mother and child. Like many other antepartum complications, PE and GDM occur only in pregnancy. However, it is not clear if pregnancy itself is the cause of these complications or it these conditions are caused by factors that existed prior to gestation. In this paper, we hypothesize that although the clinical findings of PE and GDM are first noted during pregnancy, the origins of both conditions may actually precede pregnancy. We further hypothesize that pathophysiologic changes underlying PE and GDM are present prior to pregnancy, but remain undetected in the non-gravid state either because pregnancy is the trigger that makes these pathologies become clinically detectable or because there has been limited prospective longitudinal data comparing the pre-gravid and antepartum status of women that go on to develop these conditions. Rigorous prospective cohort studies in which women undergo serial systematic evaluation in the pre-conception period, throughout pregnancy and into the postpartum are ideally needed to test this hypothesis of pre-conception origins of PE and GDM. In this context, we are creating a pre-conception cohort, involving about 5000 couples who plan to have a baby within six months in Liuyang county in the Chinese province of Hunan. Results from this pre-conception cohort program should be able to provide definitive answer to the question of whether the underpinnings of PE and GDM originate prior to pregnancy. Ultimately, the significance of addressing this hypothesis is underscored by its potential implications for targeted interventions that could be designed to (i) prevent the deleterious effects of PE/GDM and (ii) thereby interrupt the vicious cycle of disease that links affected women and their offspring.


Effect of ethnicity, country of origin and workplace on health behaviors and health perception among nurses: Cross-sectional study.
The study aimed to (1) examine health behaviors and perceived health among nurses; (2) analyze the effect of nurses' personal and work characteristics on these variables; and (3) explore the relationship between health behaviors and nurses' health perception. A cross-sectional study was conducted among nurses working in health care organizations (HCOs) across Israel. An email with the online questionnaire was sent to nurses working in 19 HCOs across Israel during September-December 2018. Of 18,120 nurses employed, 3542 completed the survey. Mean age was 44.8 years, 91% were female), 64.6% were hospital nurses and 52.8% were clinical staff nurses. Two-thirds of nurses did not achieve the physical activity (PA) target; the majority reported unfavorable eating habits; 66% slept less than 7 h at night and 15% smoke. Hospital nurses working night shifts reported the least favorable health behaviors. Non-Jewish nurses had less eating habits compared with Jewish nurses. Nurses born in the Former Soviet Union perceived their health as significantly worse than that of the other respondents. Binomial logistic regression demonstrated that, age, Israeli origin, achieving the PA target, having food breaks during work, consuming a Mediterranean diet, sleeping at least 7 h, undergoing screening tests as recommended, and not smoking predicted better health perception among nurses. Nurses, particularly hospital-based, non-Jewish and immigrants from the Soviet Union, demonstrated unfavorable health behaviors that may negatively affect their wellbeing and health perception. Interventions aimed at improving the health promoting mindset of nurses have the potential to improve their health and wellbeing and to enable them to become role models and health educators for patients and their families.


Quantification of sulfur and sulfur-containing compounds in wastewaters by means of a combination of liquid chromatographic methods.
Low-micromolar concentrations of sulfite, thiosulfate and sulfide, present in synthetic wastewater or anaerobic digester effluent, were quantified by means of derivatization with monobromobimane, followed by HPLC separation with fluorescence detection. The concentration of elemental sulfur was determined, after its extraction with chloroform from the derivatized sample. by HPLC with UV detection. Recoveries of sulfide (both matrices), and of thiosulfate and sulfite (synthetic wastewater) were between 98 and 103%. The in-run RSDs on separate derivatizations were 13 and 19% for sulfite (two tests), between 1.5 and 6.6% for thiosulfate (two tests) and between 4.1 and 7.7% for sulfide (three tests). Response factors for derivatives of sulfide and thiosulfate, but not sulfite, were steady over a 13-month period during which 730 samples were analysed. Dithionate and tetrathionate did not seem to be detectable with this method. The distinctness of the elemental sulfur and the derivatizing-agent peaks was improved considerably by detecting elution at 297 instead of 263 nm.


Combined pars plana vitrectomy with phacoemulsification for rhegmatogenous retinal detachment repair.
To investigate the outcome after combined phaco-vitrectomy in rhegmatogenous retinal detachment (RRD) repair. In this retrospective study, we included all patients who underwent pars plana vitrectomy (PPV) for RRD between January 2013 and December 2017. The main outcome measure was the retinal re-detachment rate after combined phaco-vitrectomy. Overall, 1017 eyes with RRD were included. All eyes received PPV, while in 516 eyes additional phacoemulsification was performed. A retinal re-detachment occurred in 103 patients (10.1%). No significant difference in the rate of re-detachment was found if additional phacoemulsification was performed (p=0.641). Subgroup calculations showed a significant higher rate of re-detachment in patients with a PVR (p=0.0003) and in patients where silicone oil was used as primary tamponade (p=0.0001) as well as in macula off RRDs (p=0.034). Additional phacoemulsification during vitrectomy for RRD is not associated with higher rate of retinal re-detachment.


Screening devices for diminished cognitive capacity.
This study compares three commonly used tests to detect organic mental disorders: the Mini-Mental State (MMS), Cognitive Capacity Screening Examination (CCSE), and Tachistoscope (T-Scope). Ninety-seven medical-surgical inpatients at the Mount Sinai Hospital referred for psychiatric consultation had a Missouri Mental Status Examination performed by a psychiatrist who also rated the patients' organic mental disorder as "none," "mild," "moderate," or "severe." The CCSE, MMS, and T-Scope, respectively, showed: sensitivity--0.54, 0.52, 0.68; specificity--0.85, 0.76, 0.79; and positive predictive value--0.83, 0.74, 0.79. False negatives occurred more often among those patients with mild organic mental disorders with all instruments (p = 0.05), while the T-Scope could not be administered in 27% of the patients. Screening instruments with increased acceptability, sensitivity, and specificity need to be developed to identify a potentially life-threatening disorder.


Relationship between KIR genotypes and HLA-ligands with SARS-CoV-2 infection in the Saudi population.
To ascertain whether killer cell immunoglobulin-like receptors (KIR) genes polymorphisms and HLA-I ligands are associated with COVID-19 in Saudi Arabia. Eighty-seven COVID-19 patients who tested positive for SARS-CoV-2 and one hundred and fourteen healthy controls were enrolled in this study for genotyping of the 16 KIR genes, HLA-C1 and -C2 allotypes and HLA-G 14-bp indels polymorphisms using the sequence specific primer polymerase chain reaction (SSP-PCR) method. KIR genotype frequency differences and combination KIR-HLA-C ligand were tested for significance. Framework genes KIR2DL4, KIR3DL2, KIR3DL3, and KIR3DP2 were present in all individuals. The frequencies of KIR2DL2 and KIR2D4 were higher in COVID-19 positive patients than in healthy individuals. The frequencies of the combination KIR2DL2-HLA-C2 was also significantly higher in patients affected by COVID-19 compared with healthy controls. It was found that the inhibitory KIR2DL2 gene in isolation or combined with its HLA-C2 ligand could be associated with susceptibility to COVID-19 in the Saudi population.


Nickel-decorated RuO2 nanocrystals with rich oxygen vacancies for high-efficiency overall water splitting.
Designing transition metal-oxide-based bifunctional electrocatalysts with excellent activity and stability for OER/HER to achieve efficient water splitting is of great importance for renewable energy technologies. Herein, a highly efficient bifunctional catalysts with oxygen-rich vacancies of nickel-decorated RuO2 (NiRuO2-x) prepared by a unique one-pot glucose-blowing approach were investigated. Remarkably, the NiRuO2-x catalysts exhibited excellent HER and OER activity at 10 mA cm-2 in alkaline solution with only a minimum overpotential of 51 mV and 245 mV, respectively. Furthermore, the NiRuO2-x overall water splitting exhibited an ultra-low voltage of 1.6 V to obtain 10 mA cm-2 and stability for more than 10 h. XPS measurement and theoretical calculations demonstrated that the introduction of Ni-dopant and oxygen vacancies make the d-band center to lie close to the Fermi energy level, the chemical bonds between the active site and the adsorbed oxygen intermediate state are enhanced, thereby lowering the reaction activation barriers of HER and OER. The assembly of solar-driven alkaline electrolyzers facilitate the application of the NiRuO2-x bifunctional catalysts.


Assumptions in ecosystem service assessments: Increasing transparency for conservation.
Conservation efforts are increasingly supported by ecosystem service assessments. These assessments depend on complex multi-disciplinary methods, and rely on a number of assumptions which reduce complexity. If assumptions are ambiguous or inadequate, misconceptions and misinterpretations may arise when interpreting results of assessments. An interdisciplinary understanding of assumptions in ecosystem service science is needed to provide consistent conservation recommendations. Here, we synthesise and elaborate on 12 prevalent types of assumptions in ecosystem service assessments. These comprise conceptual and ethical foundations of the ecosystem service concept, assumptions on data collection, indication, mapping, and modelling, on socio-economic valuation and value aggregation, as well as about using assessment results for decision-making. We recommend future assessments to increase transparency about assumptions, and to test and validate them and their potential consequences on assessment reliability. This will support the taking up of assessment results in conservation science, policy and practice.


mRNA vaccination boosts S-specific T cell memory and promotes expansion of CD45RAint TEMRA-like CD8+ T cells in COVID-19 recovered individuals.
SARS-CoV-2 infection and mRNA vaccination both elicit spike (S)-specific T cell responses. To analyze how T cell memory from prior infection influences T cell responses to vaccination, we evaluated functional T cell responses in naive and previously infected vaccine recipients. Pre-vaccine S-specific responses are predictive of subsequent CD8+ T cell vaccine-response magnitudes. Comparing baseline with post-vaccination TCRβ repertoires, we observed large clonotypic expansions correlated with the frequency of spike-specific T cells. Epitope mapping the largest CD8+ T cell responses confirms that an HLA-A∗03:01 epitope was highly immunodominant. Peptide-MHC tetramer staining together with mass cytometry and single-cell sequencing permit detailed phenotyping and clonotypic tracking of these S-specific CD8+ T cells. Our results demonstrate that infection-induced S-specific CD8+ T cell memory plays a significant role in shaping the magnitude and clonal composition of the circulating T cell repertoire after vaccination, with mRNA vaccination promoting CD8+ memory T cells to a TEMRA-like phenotype.


PAHs behavior in surface water and groundwater of the Yellow River estuary: Evidence from isotopes and hydrochemistry.
Large-scale irrigation projects have impacted the regional surface-groundwater interactions in the North China Plain (NCP). Given this concern, the aim of this study is to evaluate levels of PAH pollution, identify the sources of the PAHs, analyze the influence of surface-groundwater interactions on PAH distribution, and propose urgent management strategies for PAHs in China's agricultural areas. PAH concentrations, hydrochemical indicators and stable isotopic compositions (δ18O and δ2H) were determined for surface water (SW) and groundwater (GW) samples. PAHs concentrations in surface water and groundwater varied from 11.84 to 393.12 ng/L and 8.51-402.84 ng/L, respectively, indicating mild pollution. The seasonal variations showed the following trend: PAHs in surface water at the low-water phase > PAHs in groundwater at the low-water phase > PAHs in surface water at the high-water phase > PAHs in groundwater at the high-water phase. Hydrochemical and δ18O value of most groundwater samples distributed between the Yellow River and seawater. The mean value of mixture ratio of the Yellow River water recharge to the groundwater was 65%, few anomalous sites can reach to 90%. Surface-groundwater interactions influence the spatial distribution of PAHs in the study area. In light of the ongoing serious pollution, management practices for source control, improved control technologies, and the construction of a monitoring network to warn of increased risk are urgently needed.


How Should We Measure the Quality of Lymphadenectomy for Gastric Cancer? Anatomical Versus Numerical Criterion.
To compare anatomical with numerical criterion to measure the quality of lymphadenectomy for gastric cancer. We analyzed 447 gastric cancer patients with resectable tumor stage (R0 resection) with at least 16 examined lymph nodes. Of 447 patients, 82.6% underwent D2 lymphadenectomy for a median of total examined lymph nodes of 28. The 7-year disease-specific survival rate for the whole sample was 71.4%. Survival was significantly different between patients treated with D2 and D1 lymphadenectomy (77.4% versus 44.3%; p < 0.001) and between patients with total examined lymph nodes ≥ 28 and < 28 (74.5% versus 62.3%; p = 0.041). Anatomical criterion significantly differentiated 7-year survival in patients stratified according to a numerical parameter. We should still consider the anatomical criterion as the best item to measure the quality of lymphadenectomy for gastric cancer.


Immunological characterization of the low molecular weight gag gene proteins p19 and p15 of human T-cell leukemia-lymphoma virus (HTLV) and demonstration of human natural antibodies to them.
Small molecular weight gag gene proteins p19 and p15 of human T-cell leukemia virus (HTLV) were purified to homogeneity from density banded virus, using differential affinities to phosphocellulose at pH 7.9 and 6.5. Using specific radioimmunoassays, p19 and p15 were shown to band with HTLV on sucrose gradients. These proteins were present only in HTLV-I and in cell lines expressing HTLV-I. They were not expressed in a B-cell line from patient CR, although his T cells were HTLV producers. No significant immunological cross-reactivity was detected between these proteins and HTLV-IIMo. P19 and p15 did not share any common antigenic determinants with each other or with HTLV p24 in competition radioimmunoassays. Sera of HTLV-positive leukemia-lymphoma patients and some of their relatives also had natural antibodies to p19 and p15.


Kovanaze Intranasal Spray vs Traditional Injected Anesthetics: a Study of Pulpal Blood Flow Utilizing Laser Doppler Flowmetry.
An ideal local anesthetic would be effective, minimally reduce pulpal blood flow (PBF), and not require injection. This study compared the effects of 3% tetracaine plus 0.05% oxymetazoline nasal spray (Kovanaze; KNS) and injections using 2% lidocaine with 1:100,000 epinephrine (LE) or 3% mepivacaine plain (MP) on PBF, anesthetic efficacy, and participant preference. In a double-blind cross-over design, 20 subjects randomly received a test anesthetic and placebo at each of 3 visits (KNS/mock infiltration; mock nasal spray/LE; or mock nasal spray/MP). Nasal sprays and infiltration apical to a maxillary central incisor were delivered ipsilaterally. PBF was evaluated by laser Doppler flowmetry, and local anesthetic success was assessed with electric pulp testing. Postoperative pain levels, participant preference, and adverse events were also assessed. LE injections demonstrated significant reductions in PBF at all time intervals compared with baseline (P < .05), whereas KNS and MP did not. Pulpal anesthesia success rates were higher for LE (85%) compared with MP (35%) and KNS (5%). Participants reported significantly higher postoperative pain levels for KNS compared with LE and MP. Additionally, KNS was the least preferred of the anesthetics administered and resulted in more reported adverse events. Although KNS showed no significant effect on PBF, it was not effective in achieving pulpal anesthesia as used in this study.


A multi-centered epidemiological study evaluating the reliability of the treatment difficulty indices developed by the Japan Prosthodontic Society.
The diagnostic assessment of the level of difficulty in treating patients who need prosthodontic care is useful to establish a medico-economically efficient system with primary care dentists and prosthodontic specialists. A multi-axis assessment protocol was established using the newly established treatment difficulty indices. The protocol contains Axis I: oral physiological conditions (e.g., teeth damage and/or missing teeth); Axis II: general health and sociological conditions (e.g., medical disorders); Axis III: oral health-related quality of life (OHRQOL; e.g., oral health impact profile: OHIP); and Axis IV: psychological health (e.g., mood, anxiety, somatoform disorders). A preliminary study on the test-retest consistency of the protocol was conducted to check the levels of reliability of the indices prior to a large-scale, multi-center cohort study on the validity of the protocol. The test-retest consistency in terms of the oral physiological condition (Axis I) after data reduction was 0.82 [corrected] for patients with teeth problems, 0.73 [corrected] for partially edentulous patients, and 0.78 [corrected] for edentulous patients. The reliability for general health and sociological conditions (Axis II), OHRQOL (Axis III), and psychological health (Axis IV) were 0.88, 0.74, and 0.61, respectively. These values reflect either "sufficient agreement" or "excellent agreement" in accordance with the criteria established by Landis and Koch (1977) [1]. This protocol is the first multi-axis assessment scheme introduced for prosthodontic treatment with sufficient reliability. This new system is therefore expected to have a significant impact on future dental diagnostic nomenclature systems.


Long term risk of distant metastasis in women with non-metastatic breast cancer and survival after metastasis detection: a population-based linked health records study.
To estimate the long term risk of distant metastases (DM) for women with initial diagnoses of non-metastatic breast cancer; to estimate breast cancer-specific and overall survival for women with DM. Population-based health record linkage study. Women diagnosed with localised or regional primary breast cancer recorded in the NSW Cancer Registry, 2001-2002. Time from breast cancer diagnosis to first DM, time from first DM to death from breast cancer. time to death from any cause. 6338 women were diagnosed with non-metastatic breast cancer (localised, 3885; regional, 2453; median age, 59 years [IQR, 49-69 years]). DM were recorded (to 30 September 2016) for 1432 women (23%; median age, 62 years [IQR, 51-73 years]). The 14-year cumulative DM incidence was 22.2% (95% CI, 21.1-23.2%; localised disease: 14.3% [95% CI, 13.2-15.4%]; regional disease: 34.7% [95% CI, 32.8-36.6%]). Annual hazard of DM was highest during the second year after breast cancer diagnosis (localised disease: 2.8%; 95% CI, 2.3-3.3%; regional disease: 9.1%; 95% CI, 7.8-10.3%); from year five it was about 1% for those with localised disease, from year seven about 2% for women with regional disease at diagnosis. Five years after diagnosis, the 5-year conditional probability of DM was 4.4% (95% CI, 3.7-5.1%) for women with localised and 10.4% (95% CI, 9.1-12.0%) for those with regional disease at diagnosis. Median breast cancer-specific survival from first DM record date was 28 months (95% CI, 25-31 months); the annual hazard of breast cancer death after the first DM record declined from 36% (95% CI, 33-40%) during the first year to 14% (95% CI, 11-18%) during the fourth year since detection. DM risk declines with time from diagnosis of non-metastatic breast cancer, and the annual risk of dying from breast cancer declines with time from initial DM detection. These findings can be used to inform patients at follow-up about changes in risk over time since diagnosis and for planning health services.


Post-transfusion alloimmunization to granulocytes and platelets in Japanese patients as determined by the MPHA method.
The current occurrence of alloimmunization to granulocytes and platelets after blood transfusion is unclear due to the fact that antibody assays are cumbersome. Using the MPHA method with extracted granulocyte and platelet antigens, a randomized, blinded trial was conducted to investigate three types of alloantibodies in 431 Japanese patients receiving leukocyte-depleted blood transfusions prepared with or without our latest leukocyte-reduction filter. The frequency of granulocyte, platelet and HLA class I alloantibodies was 0.44%, 0.44% and 16.74%, respectively, in patients receiving non-filtered products and 0%, 0% and 0.49%, respectively, in patients receiving filtered products. The granulocyte antibody reacted with an antigen approximately of 51 KDa. The platelet-specific alloantibody was associated with GPIIb/IIIa and GPIa/IIa. The important factors affecting alloimmunization were the transfusion dose and the use of unfiltered platelet products.


Ribosome recycling defects modify the balance between the synthesis and assembly of specific subunits of the oxidative phosphorylation complexes in yeast mitochondria.
Mitochondria have their own translation machinery that produces key subunits of the OXPHOS complexes. This machinery relies on the coordinated action of nuclear-encoded factors of bacterial origin that are well conserved between humans and yeast. In humans, mutations in these factors can cause diseases; in yeast, mutations abolishing mitochondrial translation destabilize the mitochondrial DNA. We show that when the mitochondrial genome contains no introns, the loss of the yeast factors Mif3 and Rrf1 involved in ribosome recycling neither blocks translation nor destabilizes mitochondrial DNA. Rather, the absence of these factors increases the synthesis of the mitochondrially-encoded subunits Cox1, Cytb and Atp9, while strongly impairing the assembly of OXPHOS complexes IV and V. We further show that in the absence of Rrf1, the COX1 specific translation activator Mss51 accumulates in low molecular weight forms, thought to be the source of the translationally-active form, explaining the increased synthesis of Cox1. We propose that Rrf1 takes part in the coordination between translation and OXPHOS assembly in yeast mitochondria. These interactions between general and specific translation factors might reveal an evolutionary adaptation of the bacterial translation machinery to the set of integral membrane proteins that are translated within mitochondria.


Chlorinated phenoxyacetic acid derivatives and tetrachlorodibenzo-p-dioxin in foliage after application of 2,4,5-trichlorophenoxyacetic acid esters.
Six reforestation areas were sprayed with 2,4,5-T esters. Leaf samples from the areas were analyzed for the esters, tetrachlorodioxin, and dehalogenated phenoxyacetic acid esters. Tetrachlorodioxin was found in one leaf sample only, but the level found, relative to the amount of 2,4,5-T ester found, was lower than in the formulation material used in the study. The concentration of the dichlorophenoxyacetic acid esters present in several leaf samples was greater, relative to the 2,4,5-T ester, which indicated a photochemical breakdown of the 2,4,5-T in the environment.


Disorders of left ventricular structure and function in chronic uremia: how often, why and what to do with it?
Left ventricular (LV) structure and function abnormalities are frequent in individuals with chronic uraemia; these disorders are at increased risk of cardiovascular and overall morbidity and mortality in the pre-dialyzed population, during dialysis treatment and in renal transplant recipients. This review will attempt to summarize current knowledge of the prevalence, pathophysiological mechanisms of LV disease in chronic uraemia and to discuss useful medical strategies in this population.


[Excision skin margin and recurrence rate of skin cancer: a prospective study of 844 cases].
In order to evaluate recurrence rates after a mean follow-up period of five years, the aim of this unicentric prospective study was to collect data of the surgical procedure concerning both skin basal cell carcinomas (BCC) and squamous cell carcinomas (SCC). Eight hundred and fourty-four patients were included and data were retrospectively analyzed. During the surgical procedure, the peripheral clinical clearance margin was, respectively, 4mm for the skin basal cell carcinomas, 8 mm for the sclerodermiform type and 10mm for the squamous cell carcinomas. Basal cell carcinomas (BCC) were represented in 80% and the most frequent locations were the nasal area (30%). On average, the BCC measured 13.2mm. The peripheral histological clearance margin average was 4.1mm. The rate of recurrence was 3.8% after follow-up at an average of 36 months. Squamous cell carcinomas were represented in 20% cases and their locations were mainly located on the lips, the cheeks, the genital region and the extremities. On average, the SCC measured 22.45 mm. The peripheral histological clearance margin average was 10.26 mm. The rate of recurrence was 5% after follow-up at an average of 33 months. In our study, the rate of recurrence was less than 5% after follow-up of five years. To avoid repetitive operations and the risk of recurrence in anatomically sensitive areas, these tumors should be treated with standard wide margins chosen between 4 and 10 mm, function of the histological type.


Maladapting preschool children: identification, diagnosis, and remediation.
This article evaluates a preschool intervention program conducted as a part of the Wayne State University Preschool Project. The project's aim is (a) to provide early identification of preschool age children experiencing mental health problems, and (b) to reverse the diagnosed deficiencies, particularly among high risk children. The program was evaluated with children ranging in age from 3 to 4 years, within demographically comparable regions in the Detroit School System. Pretest and posttest measures were taken on the AML Scale and the Caldwell Preschool Inventory. Pretest scores were used to establish high risk children. A prescriptive intervention program was established within one region, aimed primarily at reducing adjustment problems among high risk children. The analysis of posttest data revealed more favorable scores among experimental children when compared to control children. In addition, evidence is provided of specific benefits for high risk children in the experimental program.


As(V) retention on soils and forest by-products and other waste materials.
As(V) retention capacity is determined by means of adsorption/desorption trials performed for coarse and fine ground mussel shell, forest and vineyard soils with or without fine shell, pine wood ash, oak wood ash, pine sawdust and slate-processing fines. Pine ash shows the highest arsenic retention potential (with >97 % adsorption and ≤1 % desorption), followed by shell-amended forest soil (adsorption between 96 and 92 %), by un-amended forest soil (adsorption between 98 and 86 %) and by the amended vineyard soil (adsorption between 92 and 75 %). Sawdust is the material with the lowest arsenic retention capacity in most cases, with un-amended vineyard soil also showing poor results. In the case of oak ash, As(V) percentage adsorption becomes higher with increasing added arsenic concentrations, while this increase in added arsenic causes lower percentage adsorption in the case of slate fines. Regarding adsorption ability, As(V) adsorption data were fitted to Freundlich and Langmuir models, showing good fitting, with pine ash and shell-amended forest soil having the highest K F values. In view of that, mussel shell amendment would be useful to increase arsenic retention on forest and vineyard soils, while pine ash could be used to retain arsenic even from wastewaters.


Combination of terlipressin and noradrenaline versus terlipressin in hepatorenal syndrome with early non-response to terlipressin infusion: A randomized trial.
Terlipressin and noradrenaline are effective in the management of hepatorenal syndrome (HRS). There are no reports on the combination of these vasoconstrictors in type-1 HRS. To evaluate terlipressin with or without noradrenaline in type-1 HRS not responding to terlipressin at 48 hours. Sixty patients were randomized to receive either terlipressin (group A; n = 30) or a combination of terlipressin and noradrenaline infusion (group B; n = 30). In group A, terlipressin infusion was started at 2 mg/day and increased by 1 mg/day (maximum 12 mg/day). In group B, terlipressin was given at a constant dose of 2 mg/day. Noradrenaline infusion was started at 0.5 mg/h at baseline and increased to 3 mg/h in a stepwise manner. The primary outcome was treatment response at 15 days. Secondary outcomes were 30-day survival, cost-benefit analysis and adverse events. There was no significant difference in the response rate between the groups (50% vs. 76.7%, p = 0.06) and 30-day survival was similar (36.7% vs. 53.3%, p = 0.13). Treatment was more expensive in group A (USD 750 vs. 350, p < 0.001). Adverse events were more frequent in group A (36.7% vs. 13.3%, p < 0.05). The combination of noradrenaline and terlipressin infusion results in a non-significantly higher rate of HRS resolution with significantly fewer adverse effects in HRS patients who do not respond to terlipressin within 48 hours. gov (NCT03822091).


[Cloning, expression and purification of neural specific HuD cDNA].
To prokaryoticly express and purify HuD protein and its RNA recognition motifs. HuD protein was prokaryoticly expressed and purified by molecular cloning technology. Its biologic activity was testified by Western Blot. Purified HuD protein and its RNA recognized motifs were observed. The result might aid for basic research and clinical application.


Comparative methylation analysis of murine transgenes that undergo or escape X-chromosome inactivation.
We analyzed an X-linked metallothionein-vasopressin (MTVP) fusion transgene that undergoes X-chromosome inactivation (X inactivation) and an X-linked transferrin (TFN) transgene that escapes X inactivation with respect to methylation in the 5' regulatory regions. The MTVP transgene promoter region is unmethylated when the transgene is on the active X chromosome and methylated when on the inactive X chromosome. Interestingly, the MTVP transgene is not detectably transcribed from the male X chromosome, although it is unmethylated, consistent with its availability for transcription. The TFN transgene promoter region is hypomethylated on both the active and inactive X chromosomes, consistent with its expression from both chromosomes. The TFN and MTVP transgenes have been mapped to chromosomal regions D and C, respectively, by fluorescence in situ hybridization. These observations are discussed in the context of our understanding of the role of DNA methylation in the spread and maintenance of X-chromosome inactivation.


Effects of sleep pattern, duration, and quality on premenstrual syndrome and primary dysmenorrhea in korean high school girls.
Sleep deprivation is known to be a risk factor for premenstrual syndrome and primary dysmenorrhea in adults. However, it has rarely been investigated in adolescents. The aim of this study was to investigate whether sleep pattern, duration, and quality independently affect premenstrual syndrome and primary dysmenorrhea in adolescent girls. An additional purpose was to investigate the sleep status in Korean adolescent girls during the COVID-19 pandemic. A cross-sectional survey study was conducted in 519 high school girls aged 15 to 18 years in Gyeonggido, South Korea, in 2021 during the COVID-19 lockdown. Menstrual pain intensity and menstrual symptoms were assessed using the visual analogue scale (VAS) and Cox menstrual symptom scale (CMSS), respectively. Premenstrual syndrome was assessed by the premenstrual symptoms screening tool (PSST). Sleep was assessed by the Pittsburgh Sleep Quality Index (PSQI). The known risk factors of dysmenorrhea, including menstrual and lifestyle characteristics and stress, were assessed as covariates. During the pandemic, approximately 68% of girls slept 7 h or less, while about 60% reported poor sleep quality. Additionally, 64% of participants had a bedtime later after 1AM, and 34% woke up later after 8AM. Late bedtime significantly affected VAS (P = 0.05), CMSS severity and frequency (both P < 0.01), and PSST symptom (P < 0.01). Waking up late affected CMSS severity (P < 0.05), PSST symptom (P = 0.05), and PSST function (P < 0.05). However, the significance of these effects disappeared after controlling for covariates. Sleeping less than 5 h affected CMSS frequency (P < 0.05) and PSST symptoms (P < 0.001). After controlling for covariates, the significance of the effect on PSST symptom remained (P < 0.05). General sleep quality and PSQI components, including subjective sleep quality, sleep latency, sleep disturbance, use of sleeping medication, and daytime dysfunction, significantly affected CMSS frequency and severity and PSST symptom after controlling for covariates (P < 0.05, P < 0.01, or P < 0.001). The multiple regression analysis revealed that among sleep characteristics, sleep quality was the most important risk factor of premenstrual syndrome and dysmenorrhea. Our study result heightens the importance of healthy sleep hygiene, especially sleep quality in the management of premenstrual syndrome and dysmenorrhea in adolescent girls.


Improved application of impulse cytophotometry for the diagnosis of urinary bladder carcinoma.
Using pulse cytophotometry, almost quantitative separation of the leucocyte fraction from DNA histograms was possible by means of an anticoincidence discrimination device, This modified technique was employed for biparametric DNA/protein measurements of voided urine samples, bladder washings, and tumour tissues. The results show a high degree of correlation between these samples so that, for tumour diagnosis from DNA histograms, voided urine specimens can be used rather than bladder washings. The criteria for the bladder tumour diagnosis are derived from DNA measurements of 32 controls and 35 tumour patients. The diagnostic sensitivity of this method is 0.91 and the specificity 0.75.


Skeletal muscle force and functional exercise tolerance before and after lung transplantation: a cohort study.
We investigated the impact of lung transplantation and outpatient pulmonary rehabilitation after lung transplantation on skeletal muscle function and exercise tolerance. Skeletal muscle force (Quadriceps force, QF), exercise tolerance (six minute walking distance, 6MWD) and lung function were assessed in 36 patients before and after lung transplantation. Seventeen male and 19 female patients (age 57 +/- 4) showed skeletal muscle weakness before the transplantation. A further 32 +/- 21% reduction was seen 1.2 (interquartile range 0.9 to 2.0) months after LTX. The number of days on the intensive care unit was significantly related to the observed deterioration in muscle force after LTX. At this time point 6MWD was comparable to pre-LTX. Rehabilitation started 37 (IQR 29 to 61) days after LTX. 6MWD and QF improved significantly (140 +/- 91 m, and 35 +/- 48%, respectively; p < 0.05) with rehabilitation. QF remained below pre-LTX values. The evolution of the 6MWD with the transplantation and the subsequent rehabilitation was less in female compared to male subjects. We conclude that muscle strength deteriorates after lung transplantation, particularly in patients with long ICU stay. Outpatient pulmonary rehabilitation is feasible after lung transplantation and leads to recovery of skeletal muscle function. In female patients this recovery is significantly less compared to male recipients.


Occupational exposure to metal compounds and lung cancer. Results from a multi-center case-control study in Central/Eastern Europe and UK.
To study the association between occupational exposure to metals including chromium, cadmium, nickel, and arsenic compounds, within a population-based study design, while adjusting for confounding factors. A population-based lung cancer case-control study in Central/Eastern Europe and UK was conducted in 1998-2003, including 2,853 cases and 3,104 controls. Exposure to 70 occupational agents was assessed by local expert-teams for all subjects. Odds ratios (OR) for exposure to dust and fumes/mist of chromium, nickel, cadmium, arsenic, as well as inorganic pigment dust and inorganic acid mist, were adjusting for smoking, age, center, sex, and exposure to other occupational agents including the metals under study. Exposure to arsenic (prevalence = 1.4%) was associated with an increased lung cancer risk ((OR) 1.65, 95% confidence interval (95% CI):1.05-2.58). For chromium dust (prevalence = 4.8%, OR: 1.25, 95% CI: 0.95-1.65), a linear upward trend for duration and cumulative exposure was observed. A weak association was observed for exposure to cadmium fumes (prevalence = 1.8%, OR: 1.19, 95% CI: 0.77-1.82), which was strongest for the highest category of cumulative exposure (OR: 2.04, 95% CI: 1.07-3.90). No increased risk was observed for inorganic acid mist, inorganic pigment dust, or nickel, after adjustment for other metals. An independent effect of nickel cannot be excluded, due to its collinearity with chromium exposure. Occupational exposure to metals is an important risk factor for lung cancer. Although the strongest risk was observed for arsenic, exposure to chromium dust was most important in terms of attributable risk due to its high prevalence.


Diterpenoid from Salvia greggii.
The structure of a diterpenoid, designated salvigresin, that was isolated from the aerial parts of Salvia greggii, has been confirmed by spectroscopic investigation and X-ray analysis.


Replacing Saturated Fat with Polyunsaturated Fat Modulates Peripheral Blood Mononuclear Cell Gene Expression and Pathways Related to Cardiovascular Disease Risk Using a Whole Transcriptome Approach.
The aim of this study is to explore the molecular mechanisms underlying the effect of replacing dietary saturated fat (SFA) with polyunsaturated fat (PUFA) on cardiovascular disease (CVD) risk using a whole transcriptome approach. Healthy subjects with moderate hypercholesterolemia (n = 115) are randomly assigned to a control diet (C-diet) group or an experimental diet (Ex-diet) group receiving comparable food items with different fatty acid composition for 8 weeks. RNA isolated from peripheral blood mononuclear cells (PBMCs) at baseline and after 8 weeks of intervention is analyzed by microarray technology (n = 95). By use of a linear regression model (n = 92), 14 gene transcripts are differentially altered in the Ex-diet group compared to the C-diet group. These include transcripts related to vascular smooth muscle cell proliferation, low-density lipoprotein receptor folding, and regulation of blood pressure. Furthermore, pathways mainly related to immune response and inflammation, signal transduction, development, and cytoskeleton remodeling, gene expression and protein function, are differentially enriched between the groups. Replacing dietary SFA with PUFA for 8 weeks modulates PBMC gene expression and pathways related to CVD risk in healthy subjects with moderate hypercholesterolemia.


HLA-A, -B, -DR haplotype frequencies from DNA typing data of 26,266 Chinese bone marrow donors.
HLA phenotypes of 26,266 Chinese individuals who were recruited as potential hematopoietic stem cell donors by the Shanghai Red Cross Marrow Donor Registry, part of the China Marrow Donor Program, were determined for HLA-A, -B, and -DRB1 alleles at low to intermediate resolution using DNA-based typing methods. The large sample size of the study allowed accurate calculation of the Chinese HLA haplotype frequencies. The observed alleles correspond to 19 HLA-A, 44 -B, and 13 -DR split antigens. The serologic equivalents of HLA-A36, -A80, -B78, and -DR18 alleles were not observed. A total of 2,241 distinct HLA-A, -B, -DRB1 haplotypes were identified. Three-locus haplotype frequency was estimated using the maximum likelihood method. The lowest haplotype frequency that can be reliably estimated at a 95% confidence level was 0.000057. Using this cutoff value, 1,220 haplotypes (54%) were statistically reliable and their cumulative haplotype frequency was 0.9730. The cumulative haplotype frequency of the remaining 1,021 haplotypes (46%) was 0.0270. A regression equation of p = 0.192 log N - 0.576 was derived to estimate the probability (p) of finding an HLA-A, -B, -DR split antigens-matched donor in a pool of N Chinese donors.


Malignant spinal cord compression in the paediatric population-a systematic review, meta-analysis.
Malignant spinal cord compression (MSCC) has been noted in 3-5% of children with primary tumours. MSCC can be associated with permanent neurological deficits and prompt treatment is necessary. Our aim was to perform a systematic review on MSCC in children < 18 years to help formulate national guidelines. A systematic review of the English language was undertaken using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Search criteria included 'MSCC in children, paediatric and metastases' for papers published between January1999 and December 2022. Isolated case reports/case series with < 10 patients were excluded. From a total of 17 articles identified, a final 7 were analysed (Level III/IV). Neuroblastoma constituted the most common cause for MSCC in children (62.7%) followed by sarcoma (14.2%). Soft tissue sarcomas were the most frequent cause of MSCC in children > 5 years old, while for neuroblastomas, the mean age of presentation was 20 months. The median age at time of diagnosis for the entire cohort of patients was 50.9 months (14.8-139). The median follow-up duration was 50.7 months (0.5-204). Motor deficits were the presenting symptom in 95.6% of children followed by pain in 65.4% and sphincter disturbance in 24%. There was a delay of about 26.05 days (7-600) between the onset of symptoms and diagnosis. A multimodality approach to treatment was utilised depending on the primary tumour. The prognosis for neurological recovery was found to be inversely proportional to the degree of neurological deficits and duration of symptoms in four studies. Neuroblastoma is the most common cause for MSCC in children (62.7%) followed by sarcoma (14.2%), whilst soft tissue sarcomas constituted the most frequent cause of MSCC in children > 5 years old. The majority of patients presented with motor deficit, followed by pain. In children with neuroblastoma /lymphoma, chemotherapy was the primary treatment. Early surgery should be a consideration with rapid deterioration of neurology despite chemotherapy. A multimodality approach including chemo-radiotherapy and surgery should be the treatment of choice in metastatic sarcomas. It is worth noting that multi-level laminectomy/decompression and asymmetrical radiation to the spine can lead to spinal column deformity in the future.


Latency jump of "relaxed" versus "contracted" motor evoked potentials as a marker of cortico-spinal maturation.
Magnetic brain stimulation was carried out in 17 children, aged from 2 to 12 years, in order to investigate the latency difference between relaxed and contracted motor evoked potentials (MEPs) as a function of age. While the latency of contracted MEPs increased in a linear fashion with age and body size, the relaxed MEP latency had a much slower "maturation," which gained the adult value at about 10-12 years of age in parallel with the acquisition of manual skills. The age-related variation of this "latency jump" appears to be a specific indicator of maturative phenomena relating to motor systems.


[Effect of emotional stress on the cardiac rhythm variability in rats].
A degree of irregularities of the heart rhythm was studied by two methods: chaos-analysis and the HRV (heart rate variability) analysis. Our study shows an individual response in 3 groups of animals: 1--animals with low initial level of chaos (correlation dimension (PD2 < 2); 2--animals with high level of chaos (PD2 > 4); and animals with middle level of chaos (2 < PD2 < 4). The first two groups proved to be more sensitive to stress than the third group. Moreover we found that the electrical stability of the heart as measured by the fibrillation threshold, was higher for the chaos third group. The animals of the first two groups had low cardiac stability and high risk of stress-induced cardiac disturbances.


Successful treatment of thyroid crisis accompanied by hypoglycemia, lactic acidosis, and multiple organ failure.
We describe a case of thyroid crisis with hypoglycemia, lactic acidosis, multiple organ failure, and disseminated intravascular coagulation--rare but severe complications of thyroid crisis. The patient was a 59-year-old Chinese woman who presented with evidence of heart failure and atrial fibrillation. Analysis of a blood sample yielded astonishing results: her blood glucose was 1.7 mmol/L, and lactate greater than 15 mmol/L with the arterial pH as 6.94. Liver enzymes (alanine aminotransferase, 1846 U/L; aspartate aminotransferase, 6242 U/L) and bilirubin elevated rapidly and dramatically. Prompt treatments such as mechanical ventilation, plasma exchange, and continuous venovenous hemofiltration were preformed, along with antithyroid medication. The patient finally survived after 3 weeks of intensive care. We herein discuss the possible mechanisms of these metabolic disorders in thyroid crisis and possible therapeutic measures that could be used to reduce mortality.


The safety of ECT in geriatric psychiatry.
Electroconvulsive therapy (ECT) is often described as an effective and safe treatment of depression in the elderly. However, we have previously reported that there may be increased morbidity in this population, particularly in the very old. This paper extends this work to a second, larger sample of 136 subjects of whom 40 are over 60 years of age. We have again found that while ECT is efficacious, complications increase with age (r = .26; P less than or equal to .003), occurring in 35% of the elderly as opposed to 18% of the younger group. This increased rate of complications appears to be accounted for by problems in the very old; six of eight subjects over 75 years of age had some untoward event. Common complications in the elderly included severe confusion, falls, and cardiorespiratory problems. Complications in the whole sample were related to health status (r = .22; P less than or equal to .008) which in turn correlated with age (r = .50; P less than or equal to .0001). Those taking a greater total number of medications and a greater number of cardiovascular medications had significantly more complications during ECT. There was no relationship between either complications and outcome or complications and the number or laterality of treatments. These findings confirm the effectiveness of ECT in the elderly but suggest there may be unappreciated risks of ECT in this population. At particular risk are the very old, those in poor general health, and those taking multiple medications, particularly cardiovascular agents.


Meta-analysis of cohort studies of baseline prehypertension and risk of coronary heart disease.
Prehypertension is a common condition, but the extent to which it increases the risk for coronary heart disease (CHD) is unclear. The aim of this study was to determine the association between baseline prehypertension and risk for CHD by performing a meta-analysis of prospective cohort studies. A systematic search of published research was conducted through January 2013, using electronic databases and bibliographies of retrieved reports. Studies were included if they reported multivariate-adjusted relative risks (RRs) and corresponding 95% confidence intervals (CIs) of CHD with respect to prehypertension. A random-effects model was used to combine the study-specific risk estimates. Eighteen studies, consisting of 934,106 participants and 14,952 cases, with a median follow-up period of 8.8 years, were included. Prehypertension was associated with a significantly elevated risk for CHD (RR 1.36, 95% CI 1.22 to 1.53). Eight studies consisting of 12 cohorts further provided risk estimates for low-range prehypertension (120/80 to 129/84 mm Hg) and high-range prehypertension (130/85 to 139/89 mm Hg) separately. The risk for CHD increased significantly in high-range prehypertensive populations (RR 1.53, 95% CI 1.19 to 1.97) but not in low-range prehypertensive populations (RR 1.16, 95% CI 0.96 to 1.42). In conclusion, prehypertension is associated with a significantly increased risk for developing CHD, particularly high-range prehypertension. Further well-designed randomized controlled trials are needed to clarify the efficacy of blood pressure reduction in subjects with prehypertension.


Comparison of DNA loop size and super-coiled domain size in human cells.
DNA loop size and super-coiled domain size in HeLa cells were investigated by the nucleoid sedimentation technique as well as by analysis of the DNA-nuclear-matrix complex. After X-irradiation, the relaxation of super-coils was not correlated with the release of DNA from the nuclear matrix. The super-coiled domain size was much larger than the average DNA loop size. To explain the results, we propose that unwinding of super-coils in a DNA loop also causes unwinding in adjacent DNA loops in spite of existing attachment sites. Alternatively, the results may be explained by assuming that only very large DNA loops determine the sedimentation behaviour of nucleoids.


Protein deficiency reduces efficacy of oral attenuated human rotavirus vaccine in a human infant fecal microbiota transplanted gnotobiotic pig model.
Low efficacy of rotavirus (RV) vaccines in developing African and Asian countries, where malnutrition is prevalent, remains a major concern and a challenge for global health. To understand the effects of protein malnutrition on RV vaccine efficacy, we elucidated the innate, T cell and cytokine immune responses to attenuated human RV (AttHRV) vaccine and virulent human RV (VirHRV) challenge in germ-free (GF) pigs or human infant fecal microbiota (HIFM) transplanted gnotobiotic (Gn) pigs fed protein-deficient or -sufficient bovine milk diets. We also analyzed serum levels of tryptophan (TRP), a predictor of malnutrition, and kynurenine (KYN). Protein-deficient pigs vaccinated with oral AttHRV vaccine had lower protection rates against diarrhea post-VirHRV challenge and significantly increased fecal virus shedding titers (HIFM transplanted but not GF pigs) compared with their protein-sufficient counterparts. Reduced vaccine efficacy in protein-deficient pigs coincided with altered serum IFN-α, TNF-α, IL-12 and IFN-γ responses to oral AttHRV vaccine and the suppression of multiple innate immune parameters and HRV-specific IFN-γ producing T cells post-challenge. In protein-deficient HIFM transplanted pigs, decreased serum KYN, but not TRP levels were observed throughout the experiment, suggesting an association between the altered TRP metabolism and immune responses. Collectively, our findings confirm the negative effects of protein deficiency, which were exacerbated in the HIFM transplanted pigs, on innate, T cell and cytokine immune responses to HRV and on vaccine efficacy, as well as on TRP-KYN metabolism.


Pulmonary Complications in Patients With Fontan Circulation: JACC Review Topic of the Week.
The Fontan operation has resulted in significant improvement in survival of patients with single ventricle physiology. As a result, there is a growing population of individuals with Fontan physiology reaching adolescence and adulthood. Despite the improved survival, there are long-term morbidities associated with the Fontan operation. Pulmonary complications are common and may contribute to both circulatory and pulmonary insufficiency, leading ultimately to Fontan failure. These complications include restrictive lung disease, sleep abnormalities, plastic bronchitis, and cyanosis. Cyanosis post-Fontan procedure can be attributed to multiple causes including systemic to pulmonary venous collateral channels and pulmonary arteriovenous malformations. This review presents the unique cardiopulmonary interactions in the Fontan circulation. Understanding the cardiopulmonary interactions along with improved recognition and treatment of pulmonary abnormalities may improve the long-term outcomes in this growing patient population. Interventions focused on improving pulmonary function including inspiratory muscle training and endurance training have shown a promising effect post-Fontan procedure.


Persistent multiple organ microcirculatory disorders in severe acute pancreatitis: experimental findings and clinical implications.
This study characterizes microcirculatory changes (capillary blood flow, capillary permeability, and leukocyte rolling) in the pancreas, colon, liver, and lungs at different stages of severe acute pancreatitis (AP) in a well-established rat model using intravital microscopy and computerized image analysis. The results demonstrate that microcirculatory disorders in severe AP are not confined to the pancreas but can also be found in the colon, liver, and lungs; that they extend beyond the early stage of AP and persist for 48 hr (and longer); and that they not only affect capillary blood flow but also involve prolonged changes of capillary permeability and leukocyte endothelial interaction. These findings may explain previous observations that therapeutic strategies aimed at enhancing microcirculation improve outcome in AP even if therapy is delayed and pancreatic necrosis can no longer be influenced. Since these systemic microcirculatory disturbances may contribute to AP-associated multiple organ dysfunction syndrome, further studies are warranted to evaluate whether improvement of microcirculation stabilizes organ function in AP and how long this may be effective after disease onset.


Diversity Forests: Using Split Sampling to Enable Innovative Complex Split Procedures in Random Forests.
The diversity forest algorithm is an alternative candidate node split sampling scheme that makes innovative complex split procedures in random forests possible. While conventional univariable, binary splitting suffices for obtaining strong predictive performance, new complex split procedures can help tackling practically important issues. For example, interactions between features can be exploited effectively by bivariable splitting. With diversity forests, each split is selected from a candidate split set that is sampled in the following way: for l = 1 , ⋯ , nsplits : (1) sample one split problem; (2) sample a single or few splits from the split problem sampled in (1) and add this or these splits to the candidate split set. The split problems are specifically structured collections of splits that depend on the respective split procedure considered. This sampling scheme makes innovative complex split procedures computationally tangible while avoiding overfitting. Important general properties of the diversity forest algorithm are evaluated empirically using univariable, binary splitting. Based on 220 data sets with binary outcomes, diversity forests are compared with conventional random forests and random forests using extremely randomized trees. It is seen that the split sampling scheme of diversity forests does not impair the predictive performance of random forests and that the performance is quite robust with regard to the specified nsplits value. The recently developed interaction forests are the first diversity forest method that uses a complex split procedure. Interaction forests allow modeling and detecting interactions between features effectively. Further potential complex split procedures are discussed as an outlook. The online version contains supplementary material available at 10.1007/s42979-021-00920-1.


The role of carbonic anhydrases in extinction of contextual fear memory.
Carbonic anhydrases (CAs; EC 22.214.171.124) are metalloenzymes present in mammals with 16 isoforms that differ in terms of catalytic activity as well as cellular and tissue distribution. CAs catalyze the conversion of CO2 to bicarbonate and protons and are involved in various physiological processes, including learning and memory. Here we report that the integrity of CA activity in the brain is necessary for the consolidation of fear extinction memory. We found that systemic administration of acetazolamide, a CA inhibitor, immediately after the extinction session dose-dependently impaired the consolidation of fear extinction memory of rats trained in contextual fear conditioning. d-phenylalanine, a CA activator, displayed an opposite action, whereas C18, a membrane-impermeable CA inhibitor that is unable to reach the brain tissue, had no effect. Simultaneous administration of acetazolamide fully prevented the procognitive effects of d-phenylalanine. Whereas d-phenylalanine potentiated extinction, acetazolamide impaired extinction also when infused locally into the ventromedial prefrontal cortex, basolateral amygdala, or hippocampal CA1 region. No effects were observed when acetazolamide or d-phenylalanine was infused locally into the substantia nigra pars compacta. Moreover, systemic administration of acetazolamide immediately after the extinction training session modulated c-Fos expression on a retention test in the ventromedial prefrontal cortex of rats trained in contextual fear conditioning. These findings reveal that the engagement of CAs in some brain regions is essential for providing the brain with the resilience necessary to ensure the consolidation of extinction of emotionally salient events.


Early stage cervical cancer: psychosocial and sexual outcomes of treatment.
Eighty-three women, mean age 45 years, successfully treated by surgery (S) or radiotherapy (RT) for stage 1b cervical cancer were assessed a mean of 97 weeks post treatment. Forty to 50% reported persistent tiredness, lack of energy and weight gain. Sixty per cent had not resumed their full premorbid functional status. Mean scores for anxiety and depression were higher than general population means and this sample scored higher for psychological distress than published data quoted for disease free cancer patients. These women reported many concerns about cervical cancer, most commonly fear of recurrent disease (91%). More than one-third blamed themselves for the disease. There were no significant differences in functional outcome or psychological status between treatment groups or by age or time since treatment. Psychological distress scores were significantly correlated with physical complaints (P < 0.001) and functional outcomes (P < 0.02). For the 61 women who were sexually active, sexual function post-treatment was rated as significantly poorer than subjectively recalled premorbid sexual function (P < 0.005). RT treated patients were more likely to report pain on intercourse and loss of enjoyment. Psychological as well as physical problems were highly correlated with sexual outcome (P < 0.01) 44% were unable to talk adequately with their partners about their experience. The majority felt they needed more information about cervical cancer, its treatment and how to help themselves rehabilitate. Forty-nine per cent would have liked to have had counselling. Even with the same physical morbidity the functional, emotional and sexual status of these women could be improved by giving more attention to their psychological and sexual concerns.


Application of a multidisciplinary and integrative weight-of-evidence approach to a 1-year monitoring survey of the Seine River.
Quality assessment of environments under high anthropogenic pressures such as the Seine Basin, subjected to complex and chronic inputs, can only be based on combined chemical and biological analyses. The present study integrates and summarizes a multidisciplinary dataset acquired throughout a 1-year monitoring survey conducted at three workshop sites along the Seine River (PIREN-Seine program), upstream and downstream of the Paris conurbation, during four seasonal campaigns using a weight-of-evidence approach. Sediment and water column chemical analyses, bioaccumulation levels and biomarker responses in caged gammarids, and laboratory (eco)toxicity bioassays were integrated into four lines of evidence (LOEs). Results from each LOE clearly reflected an anthropogenic gradient, with contamination levels and biological effects increasing from upstream to downstream of Paris, in good agreement with the variations in the structure and composition of bacterial communities from the water column. Based on annual average data, the global hazard was summarized as "moderate" at the upstream station and as "major" at the two downstream ones. Seasonal variability was also highlighted; the winter campaign was least impacted. The model was notably improved using previously established reference and threshold values from national-scale studies. It undoubtedly represents a powerful practical tool to facilitate the decision-making processes of environment managers within the framework of an environmental risk assessment strategy.


Sex differences and in vitro effects of steroids on serum aminopeptidase activities.
We studied the possible existence of physiological sex differences in serum aminopeptidase activities in mice, by evaluating the effect of gonadectomy and the in vitro response to the presence in the medium of cholesterol or steroid hormones. Alanyl- and glutamyl-aminopeptidase activities were measured in sera from male, female, orchiectomized and ovariectomized mice, incubated with substrate solutions, and compared with the same groups of serum incubated with substrate solutions including cholesterol, 17-beta-estradiol, testosterone, progesterone or hydrocortisone. Our results demonstrated highly significant sex differences, and an influence of cholesterol and steroid hormones on aminopeptidase activity. Depending on the nature of the aminopeptidase, these enzymes responded in different ways to the presence of these substances and also responded differently to gonadectomy. For alanyl-aminopeptidase activity, but not for glutamyl-aminopeptidase activity, there was a clear difference in response between males and females to incubation of the serum with steroid hormones.


Management of cap striae following challenging small incision lenticule extraction surgery - A case report.
A 24-year-old female underwent small incision lenticule extraction (SMILE) for myopic astigmatism OU. In the left eye, cap-lenticular adhesion along with tearing of the cap occurred, resulting in a gaped incision and transverse striae involving the visual axis on the first post op day. Uncorrected distance visual acuity (UDVA) was 20/32. The case was managed with interface wash and stretching of the cap, in order to iron out the striae. Post intervention, the UDVA improved to 20/20, striae resolved, and interface remained clear through a follow-up of nine months, suggesting that cap striae in SMILE may be similarly managed as the flap striae in laser-assisted in situ keratomileusis (LASIK), resulting in satisfactory visual outcomes.


Multiple myeloma presenting as space-occupying lesions of the liver.
Initial myeloma presentation as discrete liver nodules is unusual. A 59-year-old man who presented with hepatomegaly and multiple space-occupying lesions in the liver and who was found to have a lambda light chain multiple myeloma with hepatic plasmacytomas is described and a review of liver involvement in multiple myeloma is presented.


[Investigation about the taste of di, tri- and tetrahydroxy fatty acid].
Two diastereomeric 9, 10-dihydroxystearic acids, four diasteromeric 9,10,12-trishydroxystearic acids, a mixture of diastereomeric 9,10,12,13-tetrahydroxystearic acids, a mixture of 9.12,13,-trihydroxy-10 trans- and 9,10,13-trihydroxy-11-trans-octadecenoic acids (tri-OH-mixture from lipoxygenase catalysis) and the hydrogenated tri-OH mixture were tested for bitter taste. Only the tri - and tetrahydroxy acids are bitter. The taste thresholds of the saturated tri- and tetrahydroxy acids are in the range from 1.0--4.3 micron ol/ml. There are no significant differences in the taste thresholds between the four diastereomeric 9,- 10,12-trihydroxy acids. The double bond in the trihydroxy acids from the lipoxygenase catalysis enhances the bitter taste 3-fold.


Synergism between anti-angiogenic and immune checkpoint inhibitor drugs: A hypothesis.
Hepatocellular cancer (HCC) and renal cell cancer (RCC) are singularly resistant to conventional chemotherapy drugs but therapies targeting the supporting stroma have significantly altered their management. Two recent trials combining anti-angiogenic (AA) agents with immune checkpoint inhibitors (ICIs)- the IMbrave150 and IMmotion151 - have reported impressive progress over targeted agents. It has been suggested that bevacizumab, by improving tissue perfusion, changes the immune suppressive tumour microenvironment to an immune stimulatory one where the ICIs can be more effective. This hypothesis proposes an alternative explanation: That bevacizumab, by increasing tissue hypoxia, amplifies the mutational burden of the tumour by stress-induced mutagenesis, creating a hypermutator profile, which is more vulnerable to the ICI drug, atezolizumab. Additionally, ICIs are known to cause hyperprogression in some tumours, and bevacizumab could provide further benefit by starving these rapidly proliferative tumours of blood supply and nutrients.


Some special aspects of hair transplantation.
The desire for an improvement in appearance and the strong emphasis currently placed on contemporary hair styles for men, have increased the number of requests for hair transplants during the past decade. Esthetics is probably the strongest motivation.