Influence of glomerular filtration rate on the clearance of vancomycin administered by continuous infusion in burn patients.
The relationship between clearance of vancomycin administered by continuous infusion and the glomerular filtration rate (GFR) estimated by creatinine clearance (CL(Cr)) was investigated in a large cohort of burn patients. Individual vancomycin clearance (CL(Van)) was estimated from the ratio between the rate of infusion and the plasma concentration at steady state for 70 patients (149 samples). The average value of CL(Van) (7.03+/-3.79 L/h) was higher than normal values in non-burn patients. A significant relationship between CL(Van) versus CL(Cr) was found (r=0.506; P<0.001): CL(Van) (L/h)=0.0205CL(Cr)(mL/min)+3.47. From this result, a simple formula is proposed to adapt vancomycin dosage: rate of vancomycin continuous infusion (g/day)=[0.0205CL(Cr) (mL/min)+3.47] x [target vancomycin concentration at steady state (mg/L)] x (24/1000). The limits of the predictive performance of this formula are discussed, since factors other than GFR can affect vancomycin elimination. This formula could help clinicians to define the optimum vancomycin dosage, particularly in patients with disturbed renal function.


Implementing a Social Needs Screening and Referral Program Among Veterans: Assessing Circumstances & Offering Resources for Needs (ACORN).
The Department of Veterans Affairs (VA) healthcare system routinely screens Veterans for food insecurity, housing instability, and intimate partner violence, but does not systematically screen for other health-related social needs (HRSNs). To (1) develop a process for systematically identifying and addressing Veterans' HRSNs, (2) determine reported prevalence of HRSNs, and (3) assess the acceptability of HRSN screening among Veterans. "Assessing Circumstances and Offering Resources for Needs" (ACORN) is a Veteran-tailored HRSN screening and referral quality improvement initiative. Veterans were screened via electronic tablet for nine HRSNs (food, housing, utilities, transportation, legal needs, social isolation, interpersonal violence, employment, and education) and provided geographically tailored resource guides for identified needs. Two-week follow-up interviews with a purposive sample of Veterans explored screening experiences. Convenience sample of Veterans presenting for primary care at a VA urban women's health clinic and suburban community-based outpatient clinic (October 2019-May 2020). Primary outcomes included prevalence of HRSNs, Veteran-reported acceptability of screening, and use of resources guides. Data were analyzed using descriptive statistics, chi-square tests, and rapid qualitative analysis. Of 268 Veterans screened, 50% reported one or more HRSNs. Social isolation was endorsed most frequently (29%), followed by educational needs (19%), interpersonal violence (12%), housing instability (9%), and utility concerns (7%). One in five Veterans reported at least one form of material hardship. In follow-up interviews (n = 15), Veterans found screening acceptable and felt VA should continue screening. No Veterans interviewed had contacted recommended resources at two-week follow-up, although several planned to use resource guides in the future. In a VA HRSN screening and referral program, Veterans frequently reported HRSNs, felt screening was important, and thought VA should continue to screen for these needs. Screening for HRSNs is a critical step towards connecting patients with services, identifying gaps in service delivery, and informing future resource allocation.


The female paraplegic and mother-child relations.
This report deals with the problems of the rehabilitation of female paraplegics, including sexual intercourse; conception, delivery, progeny, and motherhood. Successful rehabilitation creates favourable conditions for female paraplegics to bear children. Team approach to the problems of pregnancy and delivery in paraplegia includes involvement of the gynaecologist, obstetrician and paediatrician. In Slovenia this work is entrusted to the Clinic for Gynaecology and to the Rehabilitation Institute in Ljubljana. While pregnancy in the paraplegic involves risk this does not also apply to the delivery. Complications during pregnancy or delivery do not differ from those occurring in healthy pregnant women or healthy women in labour. Usually, a paraplegic mother can meet the requirements of nursing, caring for and bringing up her children, thus there is no reason why a properly rehabilitated female paraplegic should not fulfil her life and happiness by becoming a mother.


Folding heterogeneity in the essential human telomerase RNA three-way junction.
Telomeres safeguard the genome by suppressing illicit DNA damage responses at chromosome termini. To compensate for incomplete DNA replication at telomeres, most continually dividing cells, including many cancers, express the telomerase ribonucleoprotein (RNP) complex. Telomerase maintains telomere length by catalyzing de novo synthesis of short DNA repeats using an internal telomerase RNA (TR) template. TRs from diverse species harbor structurally conserved domains that contribute to RNP biogenesis and function. In vertebrate TRs, the conserved regions 4 and 5 (CR4/5) fold into a three-way junction (TWJ) that binds directly to the telomerase catalytic protein subunit and is required for telomerase function. We have analyzed the structural properties of the human TR (hTR) CR4/5 domain using a combination of in vitro chemical mapping, secondary structural modeling, and single-molecule structural analysis. Our data suggest the essential P6.1 stem-loop within CR4/5 is not stably folded in the absence of the telomerase reverse transcriptase in vitro. Rather, the hTR CR4/5 domain adopts a heterogeneous ensemble of conformations. Finally, single-molecule FRET measurements of CR4/5 and a mutant designed to stabilize the P6.1 stem demonstrate that TERT binding selects for a structural conformation of CR4/5 that is not the dominant state of the TERT-free in vitro RNA ensemble.


Early Pheromone Experience Modifies a Synaptic Activity to Influence Adult Pheromone Responses of C. elegans.
Experiences during early development can influence neuronal functions and modulate adult behaviors [1, 2]. However, the molecular mechanisms underlying the long-term behavioral effects of these early experiences are not fully understood. The C. elegans ascr#3 (asc-ΔC9; C9) pheromone triggers avoidance behavior in adult hermaphrodites [3-7]. Here, we show that hermaphrodites that are briefly exposed to ascr#3 immediately after birth exhibit increased ascr#3-specific avoidance as adults, indicating that ascr#3-experienced animals form a long-lasting memory or imprint of this early ascr#3 exposure [8]. ascr#3 imprinting is mediated by increased synaptic activity between the ascr#3-sensing ADL neurons and their post-synaptic SMB motor neuron partners via increased expression of the odr-2 glycosylated phosphatidylinositol (GPI)-linked signaling gene in the SMB neurons. Our study suggests that the memory for early ascr#3 experience is imprinted via alteration of activity of a single synaptic connection, which in turn shapes experience-dependent plasticity in adult ascr#3 responses.


Earthworms, pesticides and sustainable agriculture: a review.
The aim of this review is to generate awareness and understand the importance of earthworms in sustainable agriculture and effect of pesticides on their action. The natural resources are finite and highly prone to degradation by the misuse of land and mismanagement of soil. The world is in utter need of a healthy ecosystem that provides with fertile soil, clean water, food and other natural resources. Anthropogenic activities have led to an increased contamination of land. The intensification of industrial and agricultural practices chiefly the utilization of pesticides has in almost every way made our natural resources concave. Earthworms help in a number of tasks that support many ecosystem services that favor agrosystem sustainability but are degraded by exhaustive practices such as the use of pesticides. The present review assesses the response of earthworm toward the pesticides and also evaluates the relationship between earthworm activity and plant growth. We strictly need to refresh and rethink on the policies and norms devised by us on sustainable ecology. In an equivalent way, the natural resources should be utilized and further, essential ways for betterment of present and future livelihood should be sought.


Multiple macroreentrant ventricular tachycardias exhibiting centrifugal endocardial activations from the scar border zone after myocardial infarction.
A 53-year-old man with a ventricular tachycardia (VT) electrical storm during the chronic phase of an extensive anteroseptal myocardial infarction underwent electrophysiologic testing and catheter ablation. An electroanatomical map during 7 induced macroreentrant VTs demonstrated multiple centrifugal endocardial activations from sites that were located at the circumferential border zone of a large scar area. Interestingly, during the radiofrequency catheter ablation of 4 of the VTs, the elimination of the substrate of the previous VTs converted one VT to another probably because those VTs might have shared a central common pathway of the macroreentrant circuit with different exits.


CUREing cancer: Development and implementation of a molecular biology-focused course-based undergraduate research experience using a cancer cell culture model.
Many students in the sciences are interested in exploring research opportunities; however, the one-on-one faculty mentorship model often lacks the ability to supervise large numbers of students. An alternative mechanism for exposing undergraduate students to the research process is participation in a Course-based Undergraduate Research Experience (CURE). CUREs promote inclusivity in research, and provide structure for both students and faculty while engaging students in scientific discovery. This study describes a model for a CURE in cancer biology, and reports student outcomes. Students utilized bioinformatics to predict targets genes of miR-100, a microRNA that is differentially expressed in a cell culture model of breast cancer metastasis. Students were required to engage with primary literature to write a grant proposal for their target gene, and then were trained to perform basic molecular biology techniques to test their individual hypotheses. Additionally, the course integrated opportunities to troubleshoot experiments and present data to the group, and culminated in a publication style scientific report discussing the results of their individual research project. Students reported significantly increased confidence in executing various molecular biology techniques and research-related skills based on pre- and post-assessment surveys. Student feedback also indicated that they gained an understanding of primary literature, experimental design, and scientific writing as a result of the course. This study supports that CUREs can be an effective pedagogy for not only engaging larger groups of students in research, but also improving their confidence and skill set in the laboratory.


Genetic [corrected] insights into the causes and classification of [corrected] cerebral palsies.
Cerebral palsy-the most common physical disability of childhood-is a clinical diagnosis encompassing a heterogeneous group of neurodevelopmental disorders that cause impairments of movement and posture that persist throughout life. Despite being commonly attributed to a range of environmental factors, particularly birth asphyxia, the specific cause of cerebral palsy remains unknown in most individuals. A growing body of evidence suggests that cerebral palsy is probably caused by multiple genetic factors, similar to other neurodevelopmental disorders such as autism and intellectual disability. Recent advances in next-generation sequencing technologies have made possible rapid and cost-effective sequencing of the entire human genome. Novel cerebral palsy genes will probably be identified as more researchers and clinicians use this approach to study individuals with undiagnosed neurological disorders. As our knowledge of the underlying pathophysiological mechanisms of cerebral palsy increases, so will the possibility of developing genomically guided therapeutic interventions.


Induction of in vitro flowering in Dendrobium Madame Thong-In (Orchidaceae) seedlings is associated with increase in endogenous N(6)-(Delta (2)-isopentenyl)-adenine (iP) and N (6)-(Delta (2)-isopentenyl)-adenosine (iPA) levels.
We analysed the endogenous cytokinin levels of Dendrobium Madame Thong-In seedlings grown in vitro during vegetative and flowering-inductive periods. HPLC was used to fractionate the extracts and radioimmunoassay (RIA) was used for assay of zeatin (Z), dihydrozeatin (DZ), N(6)-(Delta(2)-isopentenyl)-adenine (iP) and their derivatives. Coconut water used in experiments was found to contain high level (>136 pmol ml(-1)) of zeatin riboside (ZR). Protocorms and seedlings cultured in medium with coconut water were found to contain 0.5-3.9 pmol g(-1) FW of the cytokinins analysed. Seedlings (1.0-1.5 cm) cultured in flowering-inductive liquid medium containing 6-benzyladenine (BA, 4.4 muM) and coconut water (CW, 15%) contained up to 200 and 133 pmol g(-1) FW of iP and iPA, respectively. These levels were significantly higher than all other cytokinins analysed in seedlings of the same stage and were about 80- to 150-folds higher than seedlings cultured in non-inductive medium. During the transitional (vegetative to reproductive) stage, the endogenous levels of iP (178 pmol g(-1) FW) and iPA (63 pmol g(-1) FW) were also significantly higher than cytokinins in the zeatine (Z) and dihydrozeatin (DZ) families in the same seedlings. Seedlings that grew on inductive medium but remained vegetative contained lower levels of iPA. The importance of the profiles of iP and its derivatives in induction of in vitro flowering of D. Madame Thong-In is discussed.


Alpha-melanotropin hormone inhibits the binding of [3H]SCH 23390 to the dopamine D1 receptor in vitro.
We have previously demonstrated that the simultaneous presence of alpha-melanocyte stimulating hormone (alpha-MSH) and dopamine resulted in a reduction in cyclic AMP (cAMP) levels in slices containing caudate putamen and accumbens nuclei as compared to those treated only with dopamine or alpha-MSH. This study was carried out to explore if the interaction between alpha-MSH and dopamine could be explained on the basis of a direct interaction between alpha-MSH and the dopamine D1 receptor. Saturation curves for [n-methyl-3 H](R)-(+)-8 chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1 H-3-benzazepin-7-o] hemimaleate ([3H]SCH 23390) binding in the presence of increasing concentrations of alpha-MSH were performed. Nonlinear regression in the presence of alpha-MSH revealed an increased dissociation constant (Kd). The binding capacity (Bmax) was not affected by the peptide. These data suggest an apparent competitive interaction between alpha-MSH and [3H]SCH 23390 in striatal membranes on the dopamine D1 receptor; (Ki = 1.2 X 10(-7) M). The present data show that alpha-MSH could interact with the dopamine D1 receptor modulating allosterically the affinity of [3H]SCH 23390 for the receptor or by causing a change in the lipid environment of the dopamine receptor, resulting in an inhibition of the ligand binding to it.


Interpartner conflict and child abuse risk among African American and Latino adolescent parenting couples.
The goal of this study was to identify links between observed conflict interactions and risk for child abuse and harsh parenting among a multiethnic sample of adolescent mothers (14-19 years) and young fathers (14-24 years). Prior to childbirth (T1), observation-based relationship data were collected from 154 expectant adolescent couples as well as information about physical aggression between partners. Two years after childbirth (T2), data relevant to harsh disciplinary practices and child abuse-prone attitudes were collected from both young mothers and fathers. Multiple regression analyses were run to examine the correspondence between (a) couples' relationship quality prior to childbirth and (b) subsequent risk for harsh and potentially abusive parenting practices. Findings indicated that interpartner violence prior to childbirth predicted physically punitive parenting behavior for fathers, but not for mothers. Young mothers and fathers observed to be more warmly engaged with each other during their pre-birth couple interactions (T1) reported lower rates of physically punitive parenting behavior with their children at T2. Couples' hostility at T1 predicted fathers' level of observed hostility toward his child during a structured play activity at T2. Results underscore the importance of addressing the quality of couples' relations as means of preventing dysfunctional parenting practices among adolescent mothers and their partners. Adolescent mothers and their partners are at heightened risk for engaging in dysfunctional parenting, including child abuse. Focusing on pregnant adolescents and their partners, this study sought to identify interpersonal predictors of child abuse risk. Although this study did not involve administering prevention or intervention services, the goal was to test hypotheses that would inform the development of programs for young at-risk couples. The decision to recruit young couples prior to childbirth was based on the presumption that this period of time could provide a window of opportunity to administer couple-based child abuse prevention programs. Consistent with previous research on marital relations and parenting, results of this study support the idea that efforts to develop and administer preventive-intervention programs targeting at-risk couples could help reduce the occurrence of harsh parenting behavior and abuse.


Embryonic Diapause and Maternal Recognition of Pregnancy in Diapausing Mammals.
The dynamic nature of early embryonic growth is at odds with the phenomenon of mammalian embryonic diapause, because embryos in diapause are in a state of suspended animation of varying duration. The signals that control embryonic diapause differ between species, but in all cases, it acts to synchronise reproduction with external factors to maximise the survival of the offspring. This chapter provides an overview of current understanding of the control of embryonic diapause, with an emphasis on the three species about which most is known, namely, the mouse, the mink and the tammar wallaby.


A comparative study of gentamicin and netilmicin in the treatment of gram-negative infections.
Netilmicin is active in vitro against a wide variety of gram-negative bacteria, including certain gentamicin-resistant isolates, and Staphylococcus aureus. This study presents the results of a prospective, randomized, double-blinded protocol designed to determine the relative efficacy and toxicity of netilmicin and gentamicin in the therapy of gram-negative infections. The demographic make-up of both treatment groups was similar. Cure rates were 96.7 percent with netilmicin and 94.4 percent with gentamicin. Possible transient nephrotoxicity developed in nine patients receiving netilmicin and in eight patients receiving gentamicin.


Prognostic value of plasmatic tumor M2 pyruvate kinase and carcinoembryonic antigen in the survival of colorectal cancer patients.
Colorectal cancer (CRC) can be cured in most cases if diagnosed at an early stage. Carcinoembryonic antigen (CEA) remains the most widely used cancer marker for determining prognosis of CRC. Previous studies have shown that plasmatic tumor M2 pyruvate kinase (Tu M2-PK) is highly sensitive in CRC detection at an early stage and equally as good as the results for established tumor markers with clinical potential for cancer prognosis and monitoring. The aim of this study was to assess the prognostic value of Tu M2-PK in plasma using a survival analysis in combination with CEA in serum in patients newly diagnosed with CRC. The initial study included 183 patients who had a complete diagnostic colonoscopy. This cohort study was designed to evaluate the survival in patients with histologically confirmed gastrointestinal cancers (n = 41). Tu M2-PK concentrations in EDTA plasma were determined immunologically using an ELISA assay. Plasma Tu M2-PK levels were significantly higher in patients with distant metastases, stage IV for TNM score, and advanced stage (C+D) subgroups of Dukes than other subgroups. The univariate Cox's analysis showed that CEA and Tu M2-PK gave high hazard ratios for risk of death (odds ratio CEA = 3.57 and odds ratioTu M2-PK = 2.23) and comparable values in average survival time. The results for both biomarkers did not overlap. These findings suggest that plasmatic Tu M2-PK levels of more than 20 U/mL may be a predictor of death risk.


Newly Diagnosed Diabetes and Stress Glycaemia and Its' Association with Acute Coronary Syndrome.
Diabetes is diagnosed in 10-20% of patients with acute coronary syndrome (ACS) not known to be diabetics. Elevated blood glucose is an independent risk factor for cardiac events, regardless of presence of diabetes. Evaluating the prevalence of new-diagnosed DM among patients with ACS, and assessing the relationship between stress glycaemia and new diagnosed DM with in-hospital cardiac events. Prospective observational study, in patients with ACS, in whom we analyzed parameters of glycemic metabolism, clinical data, and in-hospital cardiac events. We comparatively analyzed patients according to the HgbA1C and known DM in five groups: non-DM (< 5.6%), new pre-DM (5.6-6.5%), new DM (≥ 6.5%), controlled (<7%) and uncontrolled (≥7%) known DM. 150 patients, (93 male and 57 female) were included. Impaired glucose metabolism was detected in 44.5% of patients, 7.9% of whom were newly-diagnosed DM. The highest levels of stress glycaemia were found in new and uncontrolled known DM. The in-hospital event rate was 20.7%, the mortality rate 7.3%, being the highest in new diagnosed and uncontrolled known DM patients. The prevalence of unknown DM was high among patients with ACS. Stress glycaemia and failure to achieve glycemic controlee, were an independent predictors of in-hospital cardiac events.


[Effects of post diameter on retention of post-core crown system].
To access the effects of post's diameter on the retention of post-core restorations. Thirty-three simulant roots with same length,taper and different diameter (1.305 mm, 1.830 mm, 2.175 mm and 2.700 mm respectively) were made of polymethylmethacrylate and were divided into 4 groups. The wax patterns of post-cores were manufactured and cast. The post-cores were cemented. After that, the adhesion, frictional force and restriction of the post-core restorations were measured. When the proportion of length and diameter was smaller than 4.372, the linear regression between the post's diameter and the retention of post-core crown system was F = 107.98 + 72.08D. The linear regression between the post's diameter and the adhesion was P = 9.60 + 2.22D. The linear regression between the post's diameter and the frictional force and restriction was Q = 98.37 + 69.87D. The statistical analysis of the results indicated significant difference (P < 0.05). When the proportion of length and diameter was lager than 4.372, the retention of post-core crown system increased although the post's diameter decreased. When the proportion of length and diameter was smaller than 4.372, the retention of post-core crown system increased with the decrease of the post's diameter. While the proportion was lager than a certain value, this rule did not exist.


Cyclooxygenase pathway in dermal fibroblasts from patients with metabolic disorders of peroxisomal origin.
Cyclooxygenase metabolism was studied in fibroblasts from patients with metabolic disorders of peroxisomal origin (adrenomyeloneuropathy, X-linked adrenoleukodystrophy, cerebrohepatorenal syndrome of Zellweger and rhizomelic chondrodysplasia punctata). In response to arachidonic acid (6.25-100 microM) or calcium ionophore A23187 (2.5-20 microM) prostaglandin E2 and 6-keto-prostaglandin F1 alpha are the main cyclooxygenase metabolites formed. No formation of thromboxane B2 or 2,3-dinor-thromboxane B2 was found. Apparently due to the heterogeneous nature of peroxisomal disorders no uniform pattern of cyclooxygenase metabolism and eicosanoid concentrations in cell lines from patients with peroxisomal defects was found.


Reduced expression of microtubule-associated protein 1 light chain 3 in hypertrophic scars.
Autophagy is a tightly regulated physiological process essential for cellular maintenance, differentiation, development, and homeostasis. Aberration of this process associates with the pathogeneses of several diseases in mammals. Hypertrophic scar (HS) is characterized by an abundance of collagenous tissue with hypercellularity. However, the molecular mechanism in HS formation is poorly understood. We compared the autophagic capacity in HS and its normal skin (NS) counterparts and explored the molecular mechanism of autophagy during the formation of HS. Microtubule-associated protein 1 light chain 3 (LC3) proteins in HS and NS were detected by immunohistochemistry, Western blot and quantitative real-time PCR (qPCR). The data showed that LC3 positive staining in HS was less intensive relative to NS group (p < 0.05). Three forms of LC3, with molecular weights of about 19 kDa (proLC3), 18 kDa (LC3-I) and 16 kDa (LC3-II), respectively, expressed in NS by Western blot. In contrast, only proLC3 expressed while both LC3-I and LC3-II were significantly downregulated in HS. The protein level of beclin 1 in HS was significantly lower compared with NS (p < 0.05). LC3 and beclin 1 mRNA levels in HS were significantly lower than that in NS (p < 0.05). These results suggest that the generation of LC3-I and LC3-II are interrupted in HS, and that the resultant decrease of autophagic capacity may associate with the pathogenesis of HS.


Utilization of sugars by Lactobacillus acidophilus strains.
Utilization of various carbohydrates viz., glucose, fructose, sucrose, lactose and galactose by Lactobacillus acidophilus strains was investigated in Lactobacillus Selection Broth. Maximum viable counts, acid production and sugar utilization by different test strains were in the order: glucose greater than or equal to fructose greater than sucrose greater than or equal to lactose greater than galactose. The generation time of the tested strains was shorter in glucose medium as compared to sucrose or lactose medium.


Draft Genome Sequence of the Toxic Freshwater Microcystis aeruginosa Strain PMC 728.11 (Cyanobacteria, Chroococcales).
Microcystis aeruginosa is one of the major species that cause toxic cyanobacterial blooms in freshwater systems worldwide. Here, we report the draft genome sequence of M. aeruginosa PMC 728.11, a microcystin-producing cyanobacterium isolated from the freshwater reservoir of Juanon in Valence, France. The genome sequence contains 276 contigs, consisting of 5,536,025 bp and 5,594 putative protein-coding genes, among which are several biosynthetic gene clusters encoding enzyme complexes involved in the production of various bioactive and toxic metabolites.


Step-by-step mark-up of medical guideline documents.
Approaches to formalization of medical guidelines can be divided into model-centric and document-centric. While model-centric approaches dominate in the development of clinical decision support applications, document-centric, mark-up-based formalization is suitable for application tasks requiring the 'literal' content of the document to be transferred into the formal model. Examples of such tasks are logical verification of the document or compliance analysis of health records. The quality and efficiency of document-centric formalization can be improved using a decomposition of the whole process into several explicit steps. We present a methodology and software tool supporting the step-by-step formalization process. The knowledge elements can be marked up in the source text, refined to a tree structure with increasing level of detail, rearranged into an XML knowledge base, and, finally, exported into the operational representation. User-definable transformation rules enable to automate a large part of the process. The approach is being tested in the domain of cardiology. For parts of the WHO/ISH Guidelines for Hypertension, the process has been carried out through all the stages, to the form of executable application, generated automatically from the XML knowledge base.


Effect of the COVID-19 lockdown on disease recognition and utilisation of healthcare services in the older population in Germany: a cross-sectional study.
There is little evidence about the utilisation of healthcare services and disease recognition in the older population, which was urged to self-isolate during the COVID-19 lockdown. We aimed to describe the utilisation of physician consultations, specialist referrals, hospital admissions and the recognition of incident diseases in Germany for this age group during the COVID-19 lockdown. Cross-sectional observational study. 1,095 general practitioners (GPs) and 960 specialist practices in Germany. 2.45 million older patients aged 65 or older. The number of documented physician consultations, specialist referrals, hospital admissions and incident diagnoses during the imposed lockdown in 2020 was descriptively analysed and compared to 2019. Physician consultations decrease slightly in February (-2%), increase before the imposed lockdown in March (+9%) and decline in April (-18%) and May (-14%) 2020 compared to the same periods in 2019. Volumes of hospital admissions decrease earlier and more intensely than physician consultations (-39 versus -6%, respectively). Overall, 15, 16 and 18% fewer incident diagnoses were documented by GPs, neurologists and diabetologists, respectively, in 2020. Diabetes, dementia, depression, cancer and stroke were diagnosed less frequently during the lockdown (-17 to -26%), meaning that the decrease in the recognition of diseases was greater than the decrease in physician consultations. The data suggest that organisational changes were adopted quickly by practice management but also raise concerns about the maintenance of routine care. Prospective studies should evaluate the long-term effects of lockdowns on patient-related outcomes.


[Factors influencing mixed venous oxygen saturation in intensive care].
Changes in mixed venous blood oxygen saturation (SvO2) were studied in 2 groups of patients. Group I patients (n = 10) were all hypoxaemic, suffering from acute respiratory failure, requiring that FIO2 be maintained at 1 throughout the study; respiratory and haemodynamic conditions were improved using PEEP and cardiovascular support. On the other hand, Group II patients (n = 13) were non-hypoxaemic patients with circulatory shock in whom FIO2 was gradually increased, and the haemodynamic status was improved using positive inotropic drugs (dopamine, dobutamine, adrenaline, amrinone). All 23 patients had a Swan-Ganz catheter set up for monitoring; all the usual haemodynamic and respiratory parameters were measured. Haematocrit values were kept at the same level throughout the study. Haemodynamic parameters were measured each time a new therapeutic procedure was carried out. No close relationship between SvO2 changes and changes in cardiac index or O2 consumption were found. However, a close relationship existed between changes in SvO2 and changes in O2 extraction (EAO2): SvO2 = -EAO2 + 102 (Group I; r = 0.90, n = 54); SvO2 = -1.2 EAO2 + 103 (Group II; r = 0.93, n = 66). A strong relationship was also found between changes in SvO2 and in FIO2 in each patient of Group II. In the complicated physiological set-up of an intensive care patient, SvO2 reflects oxygen extraction. A fall in SvO2 is related to an altered oxygen demand: oxygen supply ratio. In the most seriously ill patients, there is no relationship between changes in SvO2 and cardiac index.


Viral aetiology of influenza-like illness in Belgium during the influenza A(H1N1)2009 pandemic.
The purpose of this investigation was to determine the proportion of influenza-like illness (ILI) attributable to specific viruses during the influenza A(H1N1)2009 pandemic and to describe the demographic and clinical characteristics of ILI due to respiratory viruses in Belgium. Nasopharyngeal swabs were collected from ILI patients by general practitioners (GPs) and paediatricians (PediSurv) and analysed for viruses. Of 139 samples collected from children <5 years of age by PediSurv, 86 were positive, including 28 influenza (20%), 27 respiratory syncytial virus (RSV) (19%), 21 rhinovirus (17%), 12 human metapneumovirus (hMPV) (9%) and ten parainfluenza virus (PIV) (7%). Of 810 samples received from GPs, 426 were influenza (53%). Of 312 influenza-negative samples, 41 were rhinovirus (13%), 13 RSV (4%), 11 PIV (4%) and three hMPV (1%). Influenza mostly affected the 6-15 years old age group. Other respiratory viruses were commonly detected in the youngest patients. Similar clinical symptoms were associated with different respiratory viruses. Influenza A(H1N1)2009 was the most detected virus in ILI patients during the 2009-2010 winter, suggesting a good correlation between ILI case definition and influenza diagnosis. However, in children under 5 years of age, other respiratory viruses such as RSV were frequently diagnosed. Furthermore, our findings do not suggest that the early occurrence of the influenza A(H1N1)2009 epidemic impacted the RSV epidemic in Belgium.


Understanding the link between gut microbiota, dietary intake, and nutritional status in children with autism and typical development.
Gut microbiota plays a potential role in human health and different disorders such as autism spectrum disorder (ASD). Therefore, we analyzed gut bacteria composition in children with ASD and typical development (TD), and its relationship with nutritional status and dietary intake. A descriptive cross-sectional study was carried out in 3- to 12-year-old children (ASD = 30, TD = 28). Dietary intake (applying food frequency questionnaires) and body mass index-for-age (expressed in z-score) were determined. Children were divided into normal weight and excess weight (risk of overweight + overweight + obesity), and the ASD group was categorized into gluten- and casein-free diet (ASD-diet) or no diet (ASD-no diet). The relative abundance of gut bacteria was analyzed in fecal samples by 16S rRNA sequencing. Children with excess weight had lower Roseburia than normal weight. Fewer Bifidobacterium longum and higher Clostridium glycolicum were found in the ASD group compared with TD one. Participants with excess weight and ASD had lower Roseburia and Faecalibacterium prausnitzii and higher Eubacterium ventricosum and Flavonifractor plautii than the TD group with the same nutritional status. Positive and negative associations were found between the bacteria genus and species, and the intake of dairy, vegetable drinks, cereals with and without gluten, food source of proteins, fish, food source of fat, and coconut oil, in unadjusted models and after adjustment for age, diet/no diet, ASD/TD. Significant differences in microbial community composition were found between children with ASD and TD, considering their nutritional status and dietary intake.


In vitro assessment of the photo(geno)toxicity associated with Lapatinib, a Tyrosine Kinase inhibitor.
The epidermal growth factor receptors EGFR and HER2 are the main targets for tyrosine kinase inhibitors (TKIs). The quinazoline derivative lapatinib (LAP) is used since 2007 as dual TKI in the treatment of metastatic breast cancer and currently, it is used as an oral anticancer drug for the treatment of solid tumors such as breast and lung cancer. Although hepatotoxicity is its main side effect, it makes sense to investigate the ability of LAP to induce photosensitivity reactions bearing in mind that BRAF (serine/threonine-protein kinase B-Raf) inhibitors display a considerable phototoxic potential and that afloqualone, a quinazoline-marketed drug, causes photodermatosis. Metabolic bioactivation of LAP by CYP3A4 and CYP3A5 leads to chemically reactive N-dealkylated (N-LAP) and O-dealkylated (O-LAP) derivatives. In this context, the aim of the present work is to explore whether LAP and its N- and O-dealkylated metabolites can induce photosensitivity disorders by evaluating their photo(geno)toxicity through in vitro studies, including cell viability as well as photosensitized protein and DNA damage. As a matter of fact, our work has demonstrated that not only LAP, but also its metabolite N-LAP have a clear photosensitizing potential. They are both phototoxic and photogenotoxic to cells, as revealed by the 3T3 NRU assay and the comet assay, respectively. By contrast, the O-LAP does not display relevant photobiological properties. Remarkably, the parent drug LAP shows the highest activity in membrane phototoxicity and protein oxidation, whereas N-LAP is associated with the highest photogenotoxicity, through oxidation of purine bases, as revealed by detection of 8-Oxo-dG.


Immunoglobulins in tissues of human benign prostatic hypertrophy.
The concentrations of immunoglobulins (IgG, IgA and IgM) have been determined in tissues of human benign prostatic hypertrophy by means of different immunological techniques. Results obtained show that IgA is quantitatively the most important immunoglobulin in prostatic tissue. Treatment with anti-androgens can change the Ig-pattern, in particular the levels of IgA and IgM.


Impact of behavioral contingency management intervention on coping behaviors and PTSD symptom reduction in cocaine-addicted homeless.
The purpose of this study was to examine changes in posttrauma symptoms among 118 homeless cocaine-dependent adults participating in a randomly controlled trial studying effective treatments for dually diagnosed homeless individuals. Among those with trauma exposure and PTSD symptoms, the group receiving more behaviorally intensive, contingency management treatment had significantly greater reductions in PTSD symptomatology than did the group receiving less-intensive treatment. Regression analyses revealed that greater positive distraction coping and lower negative avoidance coping at baseline, in addition to changes in avoidance coping over the 6-month study period, were significantly related to greater symptom and severity reductions. The study provides some initial evidence of important treatment outcomes other than abstinence in addiction-related interventions.


Angiogenesis gene expression in mouse uterus during the common pathway of parturition.
The objective of the study was to investigate changes in the expression of angiogenesis-related genes during the common terminal pathway of parturition including spontaneous labor at term, as well as preterm labor (PTL), induced by either bacteria or ovariectomy. Preterm pregnant mice (14.5 days of gestation) were treated with the following: (1) intrauterine injection of media; (2) intrauterine injection of heat-inactivated Escherichia coli; (3) ovariectomy; and (4) sham operation. Tissues from mice at term (19.5 days of gestation) were collected at term not in labor, term in labor, and 12 hours postpartum. Angiogenesis-related gene expression levels were quantitated by the measurement of specific mRNAs in uterine tissue by RT-qPCR and analyzed by repeated-measures analysis of variance. The following results were found: (1) microarray analysis of the uterine transcriptome indicated an enrichment for the gene ontology category of angiogenesis in bacteria-induced PTL samples (P < or = .093); (2) several genes related to angiogenesis demonstrated significantly increased expression in samples in either term spontaneous labor or preterm labor; and (3) qRT-PCR measurements demonstrated that spontaneous term labor and preterm labor induced by either bacteria or ovariectomy all substantially increased the expression of multiple angiogenesis-related genes (P < or = .0003; Angpt2, Ctgf, Cyr61, Dscr1, Pgf, Serpine1, Thbs1, and Wisp 1). Spontaneous labor at term, as well as pathologically induced preterm labor, all result in greatly increased expression of angiogenesis-related genes in the uterus.


A closed form shape function describing 3D settlement field around a deep excavation in sand.
Soil movements produced around deep excavations are one of the main issues to be addressed during design and construction of underground structures in urban environment. Several methods to predict ground movements are currently available. Semi-empirical methods correlate displacements and simple geometrical features of the excavation; these methods predict separately transversal and longitudinal settlement troughs or at least provide a conservative envelope of them and they are mainly based on empirical data of excavations in clay. Numerical methods based on the solutions of FEM or DFM models usually provide prediction of the green field subsidence. In this paper existing 2D semi-empirical methods are first shortly reviewed. Some of these methods are then modified and combined into a new 3D analytical description of the subsidence trough around a deep excavation. The proposed two variable subsidence function depends on several parameters: four independent parameters defining the overall shape and the maximum settlement acting as a scale parameter. Settlement fields reproduced by a 3D FEM nonlinear parametric study of deep excavations inspired by real case studies are thus presented and discussed. The newly proposed 3D analytical description is applied to fit the FEM results and some fundamental relationships among geometrical features of the excavation pit and the 3D shape function parameters are identified. These relationships are validated via the application to three case studies of deep excavations in sand where the subsidence was controlled by the deformation of the retaining structures finding a satisfactory and encouraging agreement.


Outcomes in young South Asian Canadians after acute myocardial infarction.
South Asians have a high prevalence of ischemic heart disease and experience high incident acute myocardial infarction (AMI) rates at younger ages than their white counterparts. The aim of this study was to compare outcomes after AMI in a Canadian population of South Asian and white patients, aged 20 to 55 years. Using hospital discharge abstract administrative data, we included patients with incident AMI, residing in British Columbia and the Calgary Health Region, between April 1, 1995 and March 31, 2002. The cohort was followed for up to 8 years (mean 4.2 years) to determine outcomes of mortality, recurrent AMI, and congestive heart failure (CHF) requiring hospitalization. South Asian ethnicity was determined using validated surname analysis. Baseline demographic characteristics and comorbidities were adjusted using Cox proportional hazard models. Of 7135 young patients with AMI, 487 were of South Asian ancestry. Compared with white patients, South Asian patients were more likely to have diabetes (25% vs. 12%) and hypertension (24% vs. 20%). After adjustment for sociodemographic and comorbidity variables, there were no significant differences in rates of 30-day mortality (risk adjusted hazard ratio [aHR] 0.90; 95% confidence interval [CI], 0.38-2.10), long-term mortality (aHR 0.81; 95% CI, 0.53-1.26), recurrent AMI (aHR 1.07; 95% CI, 0.89-1.29), or CHF (aHR 0.90; 95% CI, 0.51-1.59) between the 2 groups. Despite the recognition of increased cardiovascular mortality among young South Asian patients, our Canadian sample demonstrated similar rates of fatal and nonfatal outcomes among young South Asian and white patients with AMI.


Nanoscale insights into full-length prion protein aggregation on model lipid membranes.
The aggregates of the full-length human recombinant prion protein (PrP) (23-231) on model membranes were investigated by combining the atomic force microscopy (AFM) measurements and theoretical calculations at pH 5.0, showing the great effect of PrP concentration on its supramolecular assemblies on the lipid bilayer.


Elevated plasma concentrations of protease inhibitors and nonnucleoside reverse transcriptase inhibitors in patients coinfected with human immunodeficiency virus and hepatitis B or C: case series and literature review.
To evaluate antiretroviral pharmacokinetics in patients who are coinfected with human immunodeficiency virus (HIV) and hepatitis B and/or C virus. Specifically, we sought to determine whether coinfection results in higher than expected concentrations of protease inhibitors and nonnucleoside reverse transcriptase inhibitors (NNRTIs). Case series. Human immunodeficiency virus clinic. Twenty-six patients infected with HIV and hepatitis B and/or C virus. Patients' plasma trough concentrations (Cmeasured) of protease inhibitors and NNRTIs were compared with population average trough concentrations reported in the literature (Cpredicted). Trough concentrations were obtained irrespective of the patients' liver function. A concentration ratio of Cmeasured: Cpredicted was determined for each patient. The mean concentration ratio of the 26 patients was 1.43 (95% confidence interval 1.08-1.78). For the six patients taking nelfinavir, the ratio of nelfinavir's active metabolite (M8): parent drug was calculated. The median M8:nelfinavir ratio for these six patients was 69% lower than what has been reported in a general HIV population. These preliminary findings suggest that trough concentrations of protease inhibitors and NNRTIs may be elevated in patients with HIV infection who are coinfected with hepatitis B and/or C, compared with a general population of patients with HIV infection. Until further investigation defines the relationship between coinfection, metabolic dysfunction, and increased antiretroviral exposure, therapeutic drug monitoring may be helpful to identify coinfected patients at risk for antiretroviral toxicity secondary to elevated plasma drug concentrations.


MicroRNA-655-3p functions as a tumor suppressor by regulating ADAM10 and β-catenin pathway in Hepatocellular Carcinoma.
Increasing evidence suggests that microRNAs (miRNAs) play critical roles in malignant transformation, tumor progression and metastasis. Aberrant miR-655-3p expression has been associated with several cancers. However, the role and underlying mechanism of miR-655-3p in the development of hepatocellular carcinoma (HCC) remains unclear. MiR-655-3p expression was detected by quantitative RT-PCR (qRT-PCR) in human HCC tissues and cell lines. Cell proliferation was investigated using MTT and colony formation assays, and cell migration and invasion abilities were evaluated by transwell assay. ADAM10 protein expression was detected by immunohistochemical assay. The target gene and downstream of miR-655-3p were determined by qRT-PCR, western blot and dual-luciferase reporter assays. miR-655-3p was significantly down-regulated in HCC tissues and HCC cell lines. Low miR-655-3p expression was negatively related to tumor size, portal vein tumor thrombosis (PVTT) status, TNM stage and metastasis status. In addition, miR-655-3p overexpression and depletion decreased and increased HCC cell proliferation, migration and invasion, respectively. Moreover, ADAM10 was identified as a direct target of miR-655-3p, and miR-655-3p down-regulated E-cadherin protein level and inhibits β-catenin pathway by mediating ADAM10. MiR-655-3p might functions as a tumor suppressor by directly targeting ADAM10 and indirectly regulating β-catenin pathway in the development of progression of HCC. It may be a novel therapeutic candidate target to in HCC treatment.


Auditory-steady-state response reliability in the audiological diagnosis after neonatal hearing screening.
Conventional audiometry is the gold standard for quantifying and describing hearing loss. Alternative methods become necessary to assess subjects who are too young to respond reliably. Auditory evoked potentials constitute the most widely used method for determining hearing thresholds objectively; however, this stimulus is not frequency specific. The advent of the auditory steady-state response (ASSR) leads to more specific threshold determination. The current study describes and compares ASSR, auditory brainstem response (ABR) and conventional behavioural tone audiometry thresholds in a group of infants with various degrees of hearing loss. A comparison was made between ASSR, ABR and behavioural hearing thresholds in 35 infants detected in the neonatal hearing screening program. Mean difference scores (±SD) between ABR and high frequency ABR thresholds were 11.2 dB (±13) and 10.2 dB (±11). Pearson correlations between the ASSR and audiometry thresholds were 0.80 and 0.91 (500Hz); 0.84 and 0.82 (1000Hz); 0.85 and 0.84 (2000Hz); and 0.83 and 0.82 (4000Hz). The ASSR technique is a valuable extension of the clinical test battery for hearing-impaired children.


Assessing Appropriateness of CT and MRI Referrals for Headache and Lumbar: A Canadian Perspective on Patient-Centered Referrals.
Inappropriate diagnostic imaging is a burgeoning problem within the Canadian healthcare system and imposes considerable burdens to efficiency and timeliness of care. Low back pain and headaches affect an immense portion of the general population and have become exceedingly common complaints from patients seeking diagnostic imaging from primary care physicians. A total of 399 magnetic resonance imaging (MRI) and computed tomography (CT) requisitions for lumbar and head scans were reviewed and assessed for appropriateness in concordance with published Choosing Wisely guidelines for head and lumbar diagnostic imaging. Requisitions were classified as appropriate, inappropriate, or incomplete. Baseline data collection showed 51.6% appropriateness, 12.0% inappropriateness, and 36.3% incompleteness. New patient-centered referral forms containing evidence-based red flags by Choosing Wisely Canada were created for head and lumbar MRI and CT. The aim was to increase awareness and consideration of the guidelines during the referral process. The new referrals were distributed among 149 local family physicians in addition to information pamphlets summarizing the need to reduce unnecessary diagnostic imaging for head and lower back pain. After collection and review of 251 requisitions in the postintervention period, incomplete referrals dropped from 36.3% to 13.15%. Despite insignificant changes in appropriateness, it is promising that the intervention educated local physicians on the information required to complete the CT or MRI forms as further evidence is provided showing the efficacy of the patient-centered referrals. This study provides insight on the importance of appropriate diagnostic imaging and what methods can be used at the primary care level.


Predictors of highly prevalent brain ischemia in intracerebral hemorrhage.
This study was undertaken to determine the prevalence, characteristics, risk factors, and temporal profile of concurrent ischemic lesions in patients with acute primary intracerebral hemorrhage (ICH). Patients were recruited within a prospective, longitudinal, magnetic resonance imaging (MRI)-based study of primary ICH. Clinical, demographic, and MRI data were collected on all subjects at baseline and 1 month. Of the 138 patients enrolled, mean age was 59 years, 54% were male, 73% were black, and 84% had a history of hypertension. At baseline, ischemic lesions on diffusion-weighted imaging (DWI) were found in 35% of patients. At 1 month, lesions were present in 27%, and of these lesions, 83% were new and not present at baseline. ICH volume (p = 0.025), intraventricular hemorrhage (p = 0.019), presence of microbleeds (p = 0.024), and large, early reductions in mean arterial pressure (p = 0.003) were independent predictors of baseline DWI lesions. A multivariate logistical model predicting the presence of 1-month DWI lesions included history of any prior stroke (p = 0.012), presence of 1 or more microbleeds (p = 0.04), black race (p = 0.641), and presence of a DWI lesion at baseline (p = 0.007). This study demonstrates that >⅓ of patients with primary ICH have active cerebral ischemia at baseline remote from the index hematoma, and ¼ of patients experience ongoing, acute ischemic events at 1 month. Multivariate analyses implicate blood pressure reductions in the setting of an active vasculopathy as a potential underlying mechanism. Further studies are needed to determine the impact of these lesions on outcome and optimal management strategies to arrest vascular damage.


Calcium transport and phytate hydrolysis during chemical hardening of common bean seeds.
In this study, two chemical bean seed hardening methods were used to investigate the changes in cooking behavior associated with Ca2+ transport and phytate hydrolysis to better understand their role in the pectin-cation-phytate hypothesis. The texture evolution of fresh and hardened red kidney beans was evaluated, hardening being induced by soaking or in a CaCl2 solution (0.01 M, 0.05 M, 0.1 M) or sodium acetate buffer (0.1 M, pH 4.4, 41 °C). The beans soaked in a CaCl2 solution at higher concentrations or in sodium acetate buffer for a longer time exhibited a delayed cooking behavior. This study also explored the bio-chemical changes (calcium content in different bean substructures, phytate content and the pectin degree of methylesterification (DM) in the cotyledons) occurring in the beans during chemical hardening and cooking. The Ca2+ concentrations in the whole beans and cotyledons of beans soaked and cooked in CaCl2 solutions significantly increased while inositol hexaphosphate IP6 content showed no significant changes. This indicates that the delayed texture drop in this case results from the influx of exogenous Ca2+ in the cotyledons and seed coats during cooking while the IP6 was not hydrolyzed and did not release endogenous Ca2+. For beans soaked in sodium acetate buffer, phytate profiling showed increased hydrolysis of IP6 with longer soaking time, suggesting the migration of endogenous Ca2+ released from phytate hydrolysis contributing to the delayed cooking of these beans. These results indicate that both an exogenous Ca2+ influx during soaking and cooking and an endogenous Ca2+ replacement resulting from phytate hydrolysis can play an important role in the hardening of beans. In neither of the cases, a significant change in pectin DM was observed during chemical hardening, therefore limiting the delayed cooking to the role of Ca2+ transport. The outcome of both cases is inline with the basic principles of the pectin-cation-phytate hypothesis whereby pectin DM changes are hardly involved and different mechanisms of release/transport are involved.


Immunotherapy of cancer in single-cell RNA sequencing era: A precision medicine perspective.
Immunotherapy has revolutionized cancer treatment and brought new aspects into tumor immunology. Effective immunotherapy will require using the suitable target antigens, optimizing the interaction between the antigenic peptide, the APC, and the T cell, and the simultaneous inhibitor of the negative regulatory process that inhibits immunotherapeutic effects and develop resistance. Tumor heterogeneity and its microenvironment is the leading cause of resistance in patients. Recently by emerging the single-cell RNA sequencing technology and its combination with immunotherapy, now we can specifically evaluate the mechanism of tumors in the face of immunotherapy agents at the single-cell resolution by detecting the transcriptional activity of immune checkpoints, screening neoantigens with high transcription levels, identifying rare cells, and other important processes. This review focuses on scRNA-seq, particularly on its application in cancer immunotherapy.


Duodenopleural fistula formation after percutaneous radiofrequency ablation for recurrent hepatocellular carcinoma.
Radiofrequency ablation (RFA) is a treatment option in the management of unresectable or recurrent hepatocellular carcinoma (HCC). It can be performed either through laparotomy or in a minimally invasive manner by percutaneous, laparoscopic or thoracoscopic routes. Percutaneous RFA is associated with reduced surgical trauma and thus can be performed in patients with significant comorbidities. The procedure can be repeated after short intervals for sequential ablation of multiple liver lesions. However, the associated risks should not be underestimated. This is the first report of a rare complication of duodeno-pleural fistula after percutaneous RFA of a recurrent subcapsular HCC. The risk of bowel perforation during the ablation of subcapsular HCC requires special attention, since only the position of the tip of the electrode, but not the zone of ablation, can be assessed accurately by imaging during the procedure. Our case demonstrated that there was leakage of bowel content from the duodenal injury site into the pleural cavity through the RFA track. Subsequent uncontrolled infection resulted in empyema thoracis and led to the death of the patient.


Diffusion-weighted echo-planar MR imaging in differential diagnosis of brain tumors and tumor-like conditions.
We assess diffusion-weighted MR images in the differential diagnosis of intracranial brain tumors and tumor-like conditions. Heavily diffusion-weighted (b = 1100 or 1200 s/mm2) axial images were obtained with single-shot echo-planar technique in 93 patients with pathologically confirmed various intracranial tumors and tumor-like conditions with diffusion gradient perpendicular to the images. We compared signal intensity of the lesions with those of gray and white matter, and cerebrospinal fluid (CSF). In 29 cases (31.1%) the lesions were isointense to gray and/or white matter. However, 5 cases (5.4%) showed extremely increased signal intensity: two epidermoid cysts; two chordomas; and one brain abscess. The entire portion of a tumor was markedly hyperintense in 10 cases (10.8%): four malignant lymphomas; four medulloblastomas; one germinoma; and one pineoblastoma. A CSF-like hypointense signal was seen in many cystic tumors, and cystic or necrotic portions of tumors. A neurosarcoid granulation was the only solid lesion showing characteristically a hypointense signal like CSF. The combination of markedly hyperintense and hypointense signals was seen generally in hemorrhagic tumors. Diffusion-weighted echo-planar MR imaging is useful in the differential diagnosis of brain tumors and tumor-like conditions, and suggests specific histological diagnosis in some cases.


Determinants of Rectal Cancer Patients' Decisions on Where to Receive Surgery: a Qualitative Analysis.
Current literature suggests surgeons who perform large volumes of rectal cancer resections achieve superior outcomes, but only about half of rectal cancer resections are performed by high-volume surgeons in comprehensive hospitals. Little is known about the considerations of patients with rectal cancer when deciding where to receive surgery. A purposive sample of stage II/III rectal adenocarcinoma survivors diagnosed 2013-2015 were identified through the Iowa Cancer Registry and interviewed by telephone about factors influencing decisions on where to receive rectal cancer surgery. Fifteen survivors with an average age of 63 were interviewed: 60% were male, 53% resided in non-metropolitan areas, and 60% received surgery at low-volume facilities. Most patients considered surgeon volume and experience to be important determinants of outcomes, but few assessed it. Recommendation from a trusted source, usually a physician, appeared to be a main determinant of where patients received surgery. Patients who chose low-volume centers noted comfort and familiarity as important decision factors. Most rectal cancer patients in our sample relied on physician referrals to decide where to receive surgery. Interventions facilitating more informed decision-making by patients and referring providers may be warranted.


Distinct subcellular localization and potential role of LINE1-ORF1P in meiotic oocytes.
LINE-1 is an autonomous non-LTR retrotransposon in mammalian genomes and encodes ORF1P and ORF2P. ORF2P has been clearly identified as the enzyme supplier needed in LINE-1 retrotransposition. However, the role of ORF1P is not well explored. In this study, we employed loss/gain-of-function approach to investigate the role of LINE1-ORF1P in mouse oocyte meiotic maturation. During mouse oocyte development, ORF1P was observed in cytoplasm as well as in nucleus at germinal vesicle (GV) stage while was localized on the spindle after germinal vesicle breakdown (GVBD). Depletion of ORF1P caused oocyte arrest at the GV stage as well as down-regulation of CDC2 and CYCLIN B1, components of the maturation-promoting factor (MPF). Further analysis demonstrated ORF1P depletion triggered DNA damage response and most of the oocytes presented altered chromatin configuration. In addition, SMAD4 showed nuclear foci signal after Orf1p dsRNA injection. ORF1P overexpression held the oocyte development at MI stage and the chromosome alignment and spindle organization were severely affected. We also found that ORF1P could form DCP1A body-like foci structure in both cytoplasm and nucleus after heat shock. Taken together, accurate regulation of ORF1P plays an essential role in mouse oocyte meiotic maturation.


Minimizing visceral organ ischemia time for open repair of thoracoabdominal aortic disease: Description of a new method.
Minimizing ischemic injury during surgical repair of thoracoabdominal aortic aneurysms (TAAAs) is vital for preventing complications such as paraplegia and acute renal failure. In this report, we describe a new technique for TAAA open repair that aims to minimize visceral organ ischemia times. Unlike typical Crawford extent II TAAA open repair, which begins with aortic clamping and proceeds from the proximal to the distal anastomoses, our method reverses the anastomosis order and minimizes aortic clamping. Between January 2016 and December 2020, we used this approach in 29 patients undergoing TAAA repair. We present one of these cases, a 29-year-old patient with progressive aneurysmal dilatation of a DeBakey type III chronic aortic dissection that extended beyond the aortic bifurcation. Our technique reduced aortic cross-clamping, left heart bypass, and internal organ and spinal cord ischemia times and appears to be safe and effective.


Crystal structure of catalase HPII from Escherichia coli.
Catalase is a ubiquitous enzyme present in both the prokaryotic and eukaryotic cells of aerobic organisms. It serves, in part, to protect the cell from the toxic effects of small peroxides. Escherichia coli produces two catalases, HPI and HPII, that are quite distinct from other catalases in physical structure and catalytic properties. HPII, studied in this work, is encoded by the katE gene, and has been characterized as an oligomeric, monofunctional catalase containing one cis-heme d prosthetic group per subunit of 753 residues. The crystal structure of catalase HPII from E. coli has been determined to 2.8 A resolution. The asymmetric unit of the crystal contains a whole molecule, which is a tetramer with accurate 222 point group symmetry. In the model built, that includes residues 27-753 and one heme group per monomer, strict non-crystallographic symmetry has been maintained. The crystallographic agreement R-factor is 20.1% for 58,477 reflections in the resolution shell 8.0-2.8 A. Despite differences in size and chemical properties, which were suggestive of a unique catalase, the deduced structure of HPII is related to the structure of catalase from Penicillium vitale, whose sequence is not yet known. In particular, both molecules have an additional C-terminal domain that is absent in the bovine catalase. This extra domain contains a Rossmann fold but no bound nucleotides have been detected, and its physiological role is unknown. In HPII, the heme group is modified to a heme d and inverted with respect to the orientation determined in all previously reported heme catalases. HPII is the largest catalase for which the structure has been determined to almost atomic resolution.


In vitro and in vivo assessment of 99mTc-UBI specificity for bacteria.
Technetium-99m labeled ubiquicidin peptide 29-41 ((99m)Tc-UBI) is a cationic human antimicrobial peptide fragment that has been shown to bind bacteria in vitro and accumulates at sites of infection in experimental animals. To help determine if (99m)Tc-UBI is bound to the bacterial cell envelope by a simple nonspecific electrostatic interaction, a comparative study of the in vitro binding of (99m)Tc-UBI and two different (99m)Tc labeled cationic peptides ((99m)Tc-Tat-1-Scr and (99m)Tc-Tat-2-Scr) to bacteria and to two tumor cell line (LS174T and ACHN) was performed. The in vivo specificity of (99m)Tc-UBI for infection in mice was also evaluated using dual labels in the same animal and comparing the target/non-target ratio for (67)Ga-citrate and (99m)Tc-UBI at sites of induced infection and sterile inflammation. Under conditions of this study, the in vitro binding of (99m)Tc-UBI, (99m)Tc-Tat-1-Scr and (99m)Tc-Tat-2-Scr to S. aureus was 35, 78 and 87% respectively. While the binding of (99m)Tc-Tat-1-Scr and (99m)Tc-Tat-2-Scr was 37 and 33% to colon tumor cells (LS174T) and 39 and 41% to renal tumor cells (ACHN) respectively, the binding of (99m)Tc-UBI to both cell types was much lower at less than 4%. In vivo studies revealed that there is a significant difference (p < 0.05) in the radioactive accumulation of (99m)Tc-UBI between the sites of infection and inflammation compared to (67)Ga-citrate. Thus, (99m)Tc-UBI showed an average infection/inflammation ratio of 2.08 +/- 0.49 compared to 1.14 +/- 0.45 for (67)Ga-citrate. In conclusion, the in vitro and in vivo results provide evidence that a specific mechanism is responsible of the (99m)Tc-UBI bacterial intracellular accumulation.


The road to fully programmable protein catalysis.
The ability to design efficient enzymes from scratch would have a profound effect on chemistry, biotechnology and medicine. Rapid progress in protein engineering over the past decade makes us optimistic that this ambition is within reach. The development of artificial enzymes containing metal cofactors and noncanonical organocatalytic groups shows how protein structure can be optimized to harness the reactivity of nonproteinogenic elements. In parallel, computational methods have been used to design protein catalysts for diverse reactions on the basis of fundamental principles of transition state stabilization. Although the activities of designed catalysts have been quite low, extensive laboratory evolution has been used to generate efficient enzymes. Structural analysis of these systems has revealed the high degree of precision that will be needed to design catalysts with greater activity. To this end, emerging protein design methods, including deep learning, hold particular promise for improving model accuracy. Here we take stock of key developments in the field and highlight new opportunities for innovation that should allow us to transition beyond the current state of the art and enable the robust design of biocatalysts to address societal needs.


The effects of cholestyramine on high density lipoprotein metabolism.
This study on 4 type II hyperlipoproteinaemic subjects examines the effects of pharmacologic doses (8 g twice daily) of the bile acid sequestrant cholestyramine on the plasma distribution and chemical composition of the high density lipoprotein subfractions, HDL2 and HDL3, and describes the influence of the drug on the metabolism of the major HDL aporoteins, apolipoprotein A-I and A-II. Cholestyramine lowered plasma low density lipoprotein cholesterol (32%; P less than 0.05) without affecting the level of that lipid in very low density or high density lipoproteins. However, the plasma HDL2/HDL3 ratio and apolipoprotein A-I concentration rose significantly on treatment, while apolipoprotein A-II remained unchanged. The rise in apolipoprotein A-I derived from an increase in its synthetic rate and produced a relative enrichment of the protein with respect to apolipoprotein A-II in both HDL subfractions. These results demonstrate the cholestyramine treatment affects HDL metabolism in a way which, according to current concepts, may prove beneficial to the recipient.


[Material and technical aspects of mega prostheses].
So-called mega implants were developed especially for the therapy of tumour diseases, but since these prostheses are considered to be custom-made products, they are excluded from the usual test specifications required by the German Act on Medical Devices. Based on the fact that these mega prostheses are specially manufactured and meant to be implanted in a certain patient, only casting technologies can be used. Forging procedures commonly used for so-called normal prostheses cannot be applied here. Thus only Co-Cr-Mo cast alloys can be used. Additional technologies are used for manufacturing partial pelvic implants. By means of CT plastic models are made so that the corresponding mega implants can be properly customized afterwards. Nowadays numerous bloomed surfaces and surface structures are offered to improve the engraftment behaviour.


'Twenty syndrome' in neuromyelitis optica spectrum disorder.
A 30-year-old woman presented with recurrent hiccups, vomiting and painful diminution of vision and gait instability for 1 day. She had one-and-a-half syndrome, bilateral seventh cranial nerve paresis with bilateral symptomatic optic neuritis and left-sided ataxic haemiparesis. We described her disorder as the 'twenty syndrome' (11/2+7+7+2+2+½=20). MRI of her brain revealed demyelination predominantly in right posterolateral aspect of pons, medulla and bilateral optic nerves. Serum antiaquaporin-4 antibody came out positive. Thus, she was diagnosed as neuromyelitis optica spectrum disorder (NMOSD). She responded brilliantly to immunosuppressive therapy. This is the first ever reported case of the 'twenty syndrome' secondary to cerebral NMOSD.


[The problem of malignant branchioma. A description of three cases of degeneration or epitheliomatous metastasis within amygdaloid cervical cysts (author's transl)].
The authors describe three cases of malignant degeneration observed within amygdaloid cysts in two male and one female patient aged sixty. In one of the cases in which the cyst had been present for more than two years, there was apparently some primary degeneration, the theory favoured was that of Veau's malignant branchioma; two other cases showed metastasis of a homolateral tonsillar epithelioma within an hitherto sub-clinical amygdaloid cyst.


Prostate positioning using cone-beam computer tomography based on manual soft-tissue registration: interobserver agreement between radiation oncologists and therapists.
To check the interobserver agreement between radiation oncologists and therapists (RTT) using an on- and off-line cone-beam computer tomography (CBCT) protocol for setup verification in the radiotherapy of prostate cancer. The CBCT data from six prostate cancer patients treated with hypofractionated intensity-modulated radiotherapy (IMRT) were independently reviewed off-line by four observers (one radiation oncologist, one junior and two senior RTTs) and benchmarked with on-line CBCT positioning performed by a radiation oncologist immediately prior to treatment. CBCT positioning was based on manual soft-tissue registration. Agreement between observers was evaluated using weighted Cohen's kappa statistics. In total, 152 CBCT-based prostate positioning procedures were reviewed by each observer. The mean (± standard deviation) of the differences between off- and on-line CBCT-simCT registration translations along the three directions (antero-posterior, latero-lateral and cranio-caudal) and rotation around the antero-posterior axis were -0.7 (3.6) mm, 1.9 (2.7) mm, 0.9 (3.6) mm and -1.8 (5.0) degrees, respectively. Satisfactory interobserver agreement was found, being substantial (weighted kappa >0.6) in 10 of 16 comparisons and moderate (0.41-0.60) in the remaining six comparisons. CBCT interpretation performed by RTTs is comparable to that of radiation oncologists. Our study might be helpful in the quality assurance of radiotherapy and the optimization of competencies. Further investigation should include larger sample sizes, a greater number of observers and validated methodology in order to assess interobserver variability and its impact on high-precision prostate cancer IGRT. In the future, it should enable the wider implementation of complex and evolving radiotherapy technologies.


Surfactant-assisted mesopores in hierarchical metal-organic frameworks for the immobilization of model protein Cyt c.
A hierarchical metal-organic framework, H-mMOF-1 (representing hierarchical medi-MOF-1), was successfully synthesized by the coassembly of MOF starting reagents and a triblock copolymer surfactant F127. The obtained H-mMOF-1 retained its microporous structure but also exhibited mesopores with a size range from 3 to 10 nm. The mesopores were able to accommodate protein Cyt c with a loading capacity of 160 mg g-1. The surfactant-assisted synthesis of hierarchical MOFs provides promising applications for enzyme immobilization.


Quantifying China's iron in-use stock and its driving factors analysis.
China is experiencing unprecedented industrialization and urbanization which promotes the rapid growth of iron resource consumption and in-use stock. The material flow analysis (MFA) model and the average use life method were applied to analyze China's iron in-use stock (IIUS), and the IIUS reached 7.07 billion tons in 2016 in the reference scenario. Three driving factors of the intensity of IIUS were analyzed. Among them, the per capita IIUS was rising, and it was 5.11 t/cap in 2016 in the reference scenario. In addition, the per capita crude steel output has stabilized, which was 0.58 t/cap in 2016. The intensity of crude steel use was declining and showed the inverted U-shape. The decoupling indicator was applied to analyze the relationship between IIUS and economic growth. The decoupling of IIUS from economic growth was later than that of actual iron consumption, and the IIUS did not decoupling from economic growth in recent years. The actual iron consumption has continued to decoupling from economic growth since 2010, and the decoupling indicator peaked at 1.76 in 2015. The future per capita IIUS was predicted in different scenario and the relationship between future IIUS and GDP was analyzed. The per capita IIUS will reach saturation in 2030-2040, and the intensity of IIUS also conforms to the inverted U-shape.


Successful transcatheter arterial embolization treatment for chest wall haematoma following permanent pacemaker implantation: A case report.
Haematoma is one of the main complications associated with pacemaker implantation. Pseudoaneurysm is a rare condition that is not easy to identify and is often overlooked. A female patient diagnosed with high-grade atrioventricular block underwent permanent pacemaker implantation. During the operation, puncturing a small branch of the right subclavian artery developed into a pseudoaneurysm and resulted in further haematoma formation. Conventional treatment of compression haemostasis and haemostatic drugs was not effective. A series of timely transcatheter arterial embolizations avoided serious complications. More possible conditions should be taken into consideration as haematoma is discovered, and timely treatment might prevent severe adverse events.


The sperm epigenome: implications for the embryo.
Recent advances, including the human genome project and numerous studies of cancer and other diseases, have shown that the genetic code is not simply limited to the sequence of the four bases of DNA but also includes epigenetic programming, heritable changes that affect gene expression [Riggs A, Martinssen R, Russo V (2007) Introduction. In: Riggs A, Martinssen R, Russo V (eds) Epigenetics mechanisms of gene regulation. Cold Spring Harbor Press, New York]. The science of epigenetics is important in understanding many diseases and biological processes, including in identifying the causes of disease and better understanding the mechanisms by which the environment can affect gene expression [Carrell Fertil Steril 97 (2):267-274, 2012]. This chapter will focus on the epigenome of sperm and particularly highlight the potential role of the sperm epigenome in embryogenesis.The sperm epigenome is unique and highly specialized because of the unique nature and function of sperm and because of the diverse requirements for successful fertilization. Due to the need for motility, sperm chromatin must be compacted and highly organized. During spermiogenesis the chromatin is packaged tightly into the sperm head by the replacement of most histones with protamines. This allows for protection of the DNA from the hostile environment in the female reproductive tract. Remaining histones can have chemical modifications to the tails of the protein that either facilitate or repress gene transcription. Sperm, like embryonic stem cells, have a unique pattern of histone modifications that includes both activating and silencing marks in the promoters of genes associated with development. These bivalent marks, along with DNA hypomethylation, comprise a unique state in which the key genes are "poised" for possible activation in embryogenesis. Sperm epigenetic abnormalities have been linked with multiple diseases including male factor infertility and poor embryogenesis.


Ovarian steroids and stress produce changes in peripheral benzodiazepine receptor density.
Although past research has described changes in the density of the peripheral benzodiazepine receptor in brain and in peripheral organs in response to stressors and steroid hormone exposure, their combined influence had yet to be determined. This study examined the effect of swim-stress as a function of ovarian hormone administration on the binding of an isoquinoline carboxamide derivative, [3H]PK 11195, in brain and peripheral tissues. In olfactory bulb and adrenal gland, stress increased peripheral benzodiazepine receptor density in ovariectomized rats with and without estradiol and progesterone replacement injection, even when compared with unstressed animals treated with hormones, where estradiol + progesterone decreased peripheral benzodiazepine receptor number in olfactory bulb, but estradiol and estradiol + progesterone increased it in adrenal gland. In frontal cortex, stress decreased peripheral benzodiazepine receptor number, an effect that was reversed by estradiol. In hippocampus estradiol decreased peripheral benzodiazepine receptor density in unstressed animals and estradiol + progesterone decreased peripheral benzodiazepine receptor number in unstressed and stressed animals. In cerebellum, stress, estradiol and estradiol + progesterone alone decreased peripheral benzodiazepine receptor density. In uterus of unstressed controls, estradiol + progesterone increased peripheral benzodiazepine receptor density, and stress produced a further increase in steroid-treated females. Stress did not affect peripheral benzodiazepine receptor density in kidney, except in animals that received estradiol + progesterone injections, where swim-stress produced a significant decrease in peripheral benzodiazepine receptor density. Thus, steroid hormones regulate peripheral benzodiazepine receptor density in endocrine organs and brain, and the hormonal state of the organism modifies the peripheral benzodiazepine receptor response to stress in a tissue- and brain region-specific manner, suggesting that the peripheral benzodiazepine receptor may play a pivotal role in an integrated response to stress.


Transcriptional regulation of MMP13 by Lef1 in chondrocytes.
An association between Wnt/beta-catenin signaling and MMP13 expression has been reported but there has been little information about the underlying mechanism. Here, we investigated the role of Lef1 in IL-1beta-mediated MMP13 regulation in mouse chondrocytes. Lef1 and beta-catenin synergistically upregulated MMP13 transcription while knock-down of Lef1 using Lef1 siRNA downregulated IL-1beta-mediated MMP13 expression. Lef1 binding site was mapped to the 3' region of the MMP13 genomic locus and binding of Lef1/beta-catenin to the site was confirmed by chromatin immunoprecipitation (ChIP) assays and electrophoretic mobility shift assays (EMSAs). Furthermore, Lef1/beta-catenin binding to the Lef1 binding site transactivated MMP13 promoter activity. Our results suggest a pivotal role of Lef1/beta-catenin in MMP13 regulation in chondrocytes, which might be associated with matrix loss of degenerated arthritic cartilage.


The favorable price evolution between bare metal stents and drug eluting stents increases the cost effectiveness of drug eluting stents.
We aimed to assess the cost effectiveness of the sirolimus-eluting stent (SES) in diabetic and non-diabetic patients vs. bare metal stents (BMS). EVASTENT was a matched cohort registry of patients undergoing revascularization exclusively with SES; for each diabetic patient (db+) included, stratified according to single (SVD) or multiple (MVD) vessel disease, a non-diabetic patient (db-) was subsequently included. Efficacy, safety and cost data were obtained from the SES database, and then data from the BMS group were derived by using an original method of transition probabilities of events (Markov model and Monte Carlo simulations) if BMS had been implanted in the same patient, over a 3-year time period. Sensitivity analysis was performed by varying the price difference between BMS and SES from 2008 to 2012. In this study, 1731 patients were included with 97% complete follow-up at 3-years. In 2008, compared to BMS the SES was cost effective only in MVD db+ (7494€ per avoided revascularization (PAR) vs. >10,000€ in other groups). In 2012, after a reduction in the price difference between SES and BMS, SES were cost effective in MVD db+ (-891), SVD db+ (3519), MVD db- (3050), and SVD db- (6329) patients. Otherwise, the cardiovascular mortality rate was higher (p<0.0001) in MVD db+ than in SVD db+, MVD db- and SVD db-. The SES is now cost effective in diabetic and non-diabetic patients, after a favorable price evolution between drug eluting and bare metal stents.


Crosstalk between RNA m6A Modification and Non-coding RNA Contributes to Cancer Growth and Progression.
N6-methyladenosine (m6A) is the most common RNA modification and has an important role in normal development and tumorigenesis. The abnormal expression of m6A regulators can lead to an imbalance in m6A levels in cancer cells, leading to the dysregulated expression of oncogenes and tumor suppressor genes that may contribute to cancer development, patient response to chemoradiotherapy, and clinical prognosis. Recent studies demonstrate that non-coding RNAs are involved in epigenetic modification of both DNA and RNA in tumor cells, and may also affect the development and progression of cancer by targeting m6A regulators. In this review, we describe the functional crosstalk between m6A and non-coding RNAs, particularly microRNA, long non-coding RNA, and circular RNA, and illustrate their roles in tumor regulation. Finally, we discuss the significance of non-coding RNA and m6A modification in the diagnosis, treatment, and prognosis of cancer patients, as well as potential future research directions.


Study of the viral interference between infectious pancreatic necrosis virus (IPNV) and infectious haematopoietic necrosis virus (IHNV) in rainbow trout (Oncorhynchus mykiss).
The resistance of rainbow trout (Oncorhynchus mykiss) to an infectious haematopoietic necrosis virus (IHNV) challenge following a preceding non-lethal infection with infectious pancreatic necrosis virus (IPNV) was investigated through experimental dual infections. Trout initially infected with IPNV were inoculated 14 days later with IHNV. Single infections of trout with 1 of the 2 viruses or with cell culture supernatant were also carried out and constituted control groups. No mortality was noted in fish after a single infection with IPNV. This virus had no influence on the head kidney leucocyte phagocytic activity and plasma haemolytic complement activity. IHNV induced a high mortality (72%) and reduced the macrophage phagocytic activity and complement haemolytic activity. It also induced a late production of anti-IHNV antibodies which occurred after clearance of the virus in the fish. In trout co-infected with both viruses, a mortality rate of 2% occurred and the immune parameters were similar to those observed in the fish infected with IPNV only, demonstrating that in co-infected trout IPNV inhibits the effects of IHNV. The studied parameters did not allow us to define the mechanism of interference occurring between these 2 viruses, but some hypothesis are put forward to explain the interference between the 2 viruses.


A demographic analysis of mortality caused by the pine wood nematode (Bursaphelenchus xylophilus) and pine sawyer beetles (Monochamus alternatus) in pine forests in the Seto Inland Sea-side, Japan.
Demographic characteristics were examined in 51 study sites in naturally occurring pine populations in the Seto Inland Sea-side. The pine forests consisted on average of 51.4% Japanese red pine,Pinus densiflora, 28.9% Japanese black pine,Pinus thunbergii, and 19.7% hybrids of the two species, and occurred along an elevatinal gradient from denser, younger secondary forest regrowing after disturbance, to more mature stands at higher elevations. The proportion of dead trees did not vary much among taxa (range 24-31%). Mortality was caused primarily by the introduced pine wood nematodeBursaphelenchus xylophilus, and secondarily by its vector, the Japanese pine sawyer beetleMonochamus alternatus. While the nematode attacked individuals of all three pine taxa with equal frequency (3-8% mortality), the beetle caused the greatest proportional mortality inP. thunbergii (35%), less inP. densiflora (20%), and the least in hybrids (18%). Mortality caused by both the nematode and beetle was significantly correlated with the mean tree age, height and diameter of the dead trees.The majority (70.2%) of individuals in populations on Miyajima Island that had lived 60 or more years and survived without severe damage by nematodes and beetles were hybrids, although the proportion of hybrids in the seedlings (found only in seven out of the fifty-one study sites) was quite low (1.9%). Thus it seems that hybrids could be more long-lived and better adapted than their parental species to resist both the nematode and the beetle. IfB. xylophilus andM. alternatus populations continue to increase at their current levels they may have a drastic effect on the gene pools ofP. densiflora andP. thunbergii and on the structure and composition of Japanese pine forests.


Radio-guided occult lesion localisation using iodine 125 Seeds "ROLLIS" to guide surgical removal of an impalpable posterior chest wall melanoma metastasis.
Cancer screening and surveillance programmes and the use of sophisticated imaging tools such as positron emission tomography-computed tomography (PET-CT) have increased the detection of impalpable lesions requiring imaging guidance for excision. A new technique involves intra-lesional insertion of a low-activity iodine-125 ((125)I) seed and detection of the radioactive signal in theatre using a hand-held gamma probe to guide surgery. Whilst several studies describe using this method to guide the removal of impalpable breast lesions, only a handful of publications report its use to guide excision of lesions outside the breast. We describe a case in which radio-guided occult lesion localisation using an iodine 125 seed was used to guide excision of an impalpable posterior chest wall metastasis detected on PET-CT.


Slow pyrolysis enhances the recovery and reuse of phosphorus and reduces metal leaching from biosolids.
In this study, biochar is produced from biosolids with and without alum at a range of temperatures and simulated oxidative aging of the biochars is conducted to quantify the long-term leaching of P and metals. While biosolids containing alum had negligible amounts of plant-available P, after pyrolysis >90% of the P became immediately available for plant growth. When biosolids with no alum were converted into biochar there was a small increase in the availability of P but a larger pool was available after oxidation. Both of the biosolids leached significant amounts of metals after oxidation. In contrast, the biochars had a very low available metal content and this did not increase with oxidation, demonstrating a stable metal content. Pyrolysis is an effective waste management strategy for biosolids that can simultaneously reduce the leaching of metals and increase the efficiency of recycling of P for beneficial re-use.


The mother and the motherland: their internal representations among immigrant and non-immigrant adolescents.
This paper studies associations between internal representations that adolescents hold for their mothers and internal representations of the country they belong to, and the extent to which such internal representations impact on psychological adjustment. Two studies were conducted: the first with 328 Russian adolescents in Russia, and the second with 178 Jewish adolescent immigrants from Russia in Israel. In both samples, representations of the mother as caring were significantly related to the adolescents' positive attitudes towards their country of living. In addition, the adolescents' positive attitudes towards country of living were significantly related to their psychological adjustment, over and above internal representations of mother. Findings suggest the importance of theories of internal representations for understanding the dynamics of the adolescents' attachment to social objects and their psychological adjustment.


Willingness to pay brand premiums for generic medicines in Kenya: A bidding game experiment.
Recent growth in the market share of higher priced branded generic medicines in low- and middle-income countries (LMICs) has raised concerns around affordability and access. We examined consumer willingness to pay (WTP) for branded versus unbranded generic non-communicable disease (NCD) medicines in Kenya. We randomly assigned NCD patients to receive a hypothetical offer for either a Novartis Access-branded medicine or for an unbranded generic equivalent. We then analysed WTP data captured using a bidding game methodology. We found that WTP for Novartis Access medicines was on average 23% higher than for unbranded generic equivalents (p = 0.009). The WTP brand premium was driven almost entirely by wealthier patients. Our findings suggest that the dominance of branded generics in LMICs like Kenya reflect in part consumer preferences for these medicines. Governments and other health sector actors may be justified in intervening to improve access to these medicines and equivalent non-branded generics, particularly for the poorest patients who appear to have no preference for branded medicines.


Impacts of the COVID-19 pandemic on life expectancy at birth in Asia.
To investigate the impact of the COVID-19 pandemic on life expectancy at birth (e0) for 51 Asian countries and territories from January 1, 2020 to December 31, 2021. Based on age-sex-specific mortality used for estimating the changes in e0 for years 2019, 2020, and 2021 from the 2022 revision of the World Population Prospects, we employed Arriaga's discrete method to decompose changes in e0 into both absolute and relative contributions of changes in age-specific death rate, and further obtained the age-sex-specific contribution to changes in e0 by country/territory and period (i.e., 2019-2020 and 2020-2021) for Asia. The COVID-19 pandemic reduced 1.66 years in e0 of the Asian population from 2019 to 2021, slightly lower than the world average of 1.74 years. South Asia had a high loss of 3.01 years, whereas Eastern Asia had almost no changes. Oman, Lebanon, India, Armenia, Azerbaijan, Indonesia, and the Philippines experienced a high loss of above 2.5 years in e0. Despite significant national and territorial variations, the decline of e0 in Asia was mostly from the age group of 60-79 years, followed by age groups of 80 + and 45-59 years; and age groups of children contributed little (i.e., 0-4 and 5-14 years old). Males suffered more losses than females in this pandemic. Asian nations saw less loss in e0 in the second year of the pandemic, i.e., 2020-2021, than in the first year, i.e., 2019-2020, but this recovery trend was not observed in Southern Asia and South-Eastern Asia. Countries from Central Asia and Western Asia, such as Kazakhstan, Armenia, Azerbaijan, Lebanon, and Oman, had extraordinarily more losses in e0 in the first year at ages around 70. The COVID-19 pandemic had significantly affected e0 of Asian populations, and most contribution to the reduction of e0 came from the three older age groups, 60-79 years, 80 + years, and 45-59 years, with great variations across countries/territories. Our findings could have important implications for development of more resilient public health systems in Asian societies with better policy interventions for vulnerable demographic groups.


Specific cation effects on conformational transitions of DNA in aqueous solutions.
The circular dichroism (CD) and absorption spectral properties of calf thymus DNA have been examined in aqueous solutions containing varying concentrations of MgCl2, CaCl2, MnCl2, ZnCl2 and CoCl2. When the CD spectra were analyzed by methods previously described (Hanlon, S., Brundno, S., Wu, T.T. and Wolf, B. (1975) Biochemistry 14, 1648--1660), it was found that the spectral changes observed between 0 and 0.1 molal concentrations of each salt could be satisfactorily accounted for as a linear combination of two independent spectral components. One of these components had the spectrum which we had previously obtained in dilute solutions of NaCl (0.01-0.04 molal) and in 0.2 M tetramethyl ammonium chloride and attributed to a B-like structure. The other spectral endpoint was similar but not identical to the C spectrum obtained in the monovalent series. These differences were particularly pronounced for the transition metal ions, Mn2+, Zn2+ anc Co2+. Since significant band shifts were also observed in the absorption spectra of DNA in the presence of these transition metal ions, we have concluded that the differences observed between the C spectrum previously reported and that found for these ions is attributable to changes in the absorption properties of the monomers due to cation association, rather than dramatic differences in comformational properties of the C secondary structure of DNA in the presence of these ions. The greater efficiency of these divalent ions compared to the monovalent ions previously studied in effecting the B leads to C transconformational reaction is attributed to the more effective screening of electrostatic interactions, both along the phosphate backbone, and between sites on the bases which bear partial negative charges and the negatively charged phosphate groups. In the light of these present results, we believe that it is this electrostatic factor which is primarily involved in effecting the transition from a B to a more C-like state. The role of dehydration is viewed as a subsidiary one which facilitates better ion association, especially at the weaker base sites, thus effecting better damping of the repulsive electrostatic interactions.


The application of a potential-sensitive cyanine dye to rat small intestinal brush border membrane vesicles.
The sensitivity of the fluorescent dye, 3,3'-diethylthiadicarbocyanine (DiS-C2(5], was too low for the detection of membrane potential changes in rat small intestinal membrane vesicles. Only after adding LaCl3 or after fractionation of the intestinal membranes by free-flow electrophoresis could the dye be used to monitor electrogenic Na+-dependent transport systems. It is concluded that the response of this potential-sensitive dye is influenced by the negative surface charge density of the vesicles.


Robot-Assisted Nephrectomy Using the Newly Developed EDGE SP1000 Single-Port Robotic Surgical System: A Feasibility Study in Porcine Model.
Objectives: To evaluate the feasibility and safety of the EDGE SP1000 single-port robotic platform by performing nephrectomy in live porcine model. Materials and Methods: Robotic nephrectomy was performed on sample group of five gilts using the EDGE SP1000 single-port robotic system. The continuous vital signs of all gilts were monitored throughout the operation to examine the safety of the operation. Data regarding surgical complications and technical difficulties throughout the operation were recorded for future evaluation. Finally, the survival of the sample gilts 2 weeks after the operation were recorded. Results: The robot-assisted nephrectomy yielded an impressive result that all sample gilts survived after 2 weeks. Furthermore, neither surgical complications nor technical difficulties were encountered during the operation. The average duration to establish the operation channel was 12.4 ± 1.52 minutes, the average time taken to install EDGE SP1000 single-port robotic system was 2.8 ± 0.84 minutes, the average time to dissociate and remove the kidney was 47 ± 5.61 minutes, and average total operational duration was 71 ± 5.24 minutes. Most importantly, the surgeon and assistant who were using the system found it convenient and performed excellently during the operation. Conclusions: This study shows that the EDGE SP1000 single-port robotic surgical system is safe and feasible for the use of nephrectomy in gilts. Our further research will expand the application of the EDGE SP1000 system to other urologic procedures and accumulate more preclinical data for further clinical trial.