Effect of unilateral ureteral obstruction on metabolism of renal lipids in the rat.
The metabolism of lipids in the cortex and inner medulla of control and experimental kidneys of rats with unilateral ureteral obstruction (UUO) was studied in vitro. A marked increase in the tissue triglyceride content was noted after 24 h of obstruction in the experimental kidney compared with the contralateral kidney of rats with UUO and normal kidneys from sham-operated rats. A decrease in total phospholipid content was seen in the experimental kidney after 24 h of obstruction. The incorporation of [1-14C]oleic acid or [14C]arachidonic acid into tissue triglycerides was significantly increased in the cortex and medulla of the experimental kidney of rats with UUO compared with either the contralateral kidney of the same animals or kidneys from sham-operated rats. The oxidation of [1-14C]oleic acid to 14CO2 and the incorporation of [14C]arachidonic acid into tissue phospholipids or free fatty acids were significantly lower in the experimental kidney of rats with UUO. The results strongly suggest an increase in the net synthetic rate of triglycerides in the experimental kidney of UUO rats. This increase may be related to both a decrease in fatty acid oxidation and an increased release of fatty acids from phospholipids presumably due to increased phospholipase activity.


Modeling habitat suitability for moose in coastal northern Sweden: empirical vs process-oriented approaches.
Habitat models may provide viable tools for co-management of large ungulates and forest resources, yet their applicability has not been comprehensively evaluated in managed forest. We examined 2 inherently different approaches to model the relative winter habitat suitability for moose (Alces alces) in the coastal area of northern Sweden. An empirical approach based on GPS positions of 15 female moose was used to scrutinize the assumptions and functional mechanisms of a process-oriented, conceptual approach, based on published material on the species' preferences for habitat components related to food and cover. For both model approaches habitat was described using estimates of forest-stand characteristics based on satellite imagery. The empirical model also included variables relating to topographic properties of the landscape as well as distances to landscape features. The output from both models was a habitat suitability index (HSI) score, enabling the models to be compared with each other. The models showed different results, highlighting the need to include the spatially explicit distribution of environmental variables in future conceptual, process-oriented models.


Molecular characterization of Sp serotype strains of infectious pancreatic necrosis virus exhibiting differences in virulence.
Infectious pancreatic necrosis virus (IPNV), a prototype virus of the family Birnaviridae, exhibits a high degree of antigenic variability, pathogenicity and virulence in salmonid species. The Genomic Segment A encodes all the structural (VP2 and VP3) and nonstructural (NS) proteins, whereas Segment B encodes the viral RNA-dependent RNA polymerase (VP1). We tested 3 different IPNV isolates (Sp103, Sp116 and Sp122) isolated during field outbreaks in Norway for their ability to cause mortality in fry and post-smolt of Atlantic salmon Salmo salar L. The cumulative mortality following experimental challenge in fry was 29% for Sp122 followed by 19% for Sp116 and 15% for Sp103. In post-smolt, the corresponding mortality rates were 79, 46 and 16%, respectively. Comparisons of the deduced amino acid sequences of Segments A and B of all 3 Sp strains revealed substitutions of residues in 13 positions, of which 6 are in VP2, 2 in VP3, and 5 in VP1. Our results suggest that these residues, especially those in the outer capsid VP2, may be involved in the virulence of IPNV. Genome Segment A of the Sp serotype is 3097 nucleotides long and contains a major open reading frame (ORF) encoding a polyprotein of 972 amino acids, which initiates at the second in-frame start codon at Position 119. This was ascertained by making mutants of Segment A clone using site-directed mutagenesis, followed by in vitro transcription-coupled translation reaction and immunoprecipitation analyses. In addition, Segment A also encodes a 15 kDa arginine-rich non-structural protein from a small ORF, preceding and partially overlapping the polyprotein ORF, which is truncated to 12 kDa in the virulent Sp122 strain. Moreover, Segment A could encode a novel, putative 25 kDa protein from another ORF between VP2 and VP4 coding regions, which is only detected in the Sp serotype. Segment B is 2777 nucleotides long and encodes in a single large ORF (a polypeptide of 844 amino acid residues), VP1.


Environmental interventions reduced repetitive behavior in a mouse model.
Repetitive motor behaviors are associated with several neurodevelopmental disorders including autism spectrum disorder. Non-invasive environmental interventions that can ameliorate repetitive behavior and be introduced in early development could benefit many. In Experiment 1, we characterized the development of repetitive circling in mice reared in standard and enriched environments. Environmental enrichment was associated with reduced repetitive behavior. In Experiment 2, two weekly injections of an A2A adenosine receptor agonist reduced repetitive behavior in mice fed a ketogenic diet. Together, these two approaches modified the environment and reduced repetitive behavior with potential implications for increased functioning of the indirect basal ganglia pathway.


Impact of a community-based breast cancer screening program on Hopi women.
To examine changes in breast cancer knowledge, attitudes, beliefs and behaviors following implementation of a tribal run CDC Breast and Cervical Cancer Program (BCCP), we report 2006 survey results from Hopi women and contrast findings with 1993 survey data and BCCP reports. Community meetings, focus groups, and researchers jointly developed a culturally appropriate survey instrument. Hopi women randomly selected from Tribal enrollment lists were interviewed in-person by Hopi interviewers; 250 women ≥ age 18 participated (87% response) between June and December, 2006. Among women 40+, 77.5% reported ever having had a mammogram and 68.9% reported having done so within the past 2years, an increase from 45.2% and 46% self-reported in 1993. Compared to 1993, more women in 2006 (88.1% vs. 59%) believed that a mammogram can detect cancer and more than 90% now believe that early detection of cancer can save lives. Women reported a preference (60%) for receiving health care at the Hopi BCCP. Survey results were validated using programmatic data which estimated 76.6% of Hopi women had received mammography screening. Implementation of a tribal run BCCP has resulted in a substantial increase in mammography screening on the Hopi reservation.


Thermogenic and psychogenic recruitment of human eccrine sweat glands: Variations between glabrous and non-glabrous skin surfaces.
Human eccrine sweat-gland recruitment and secretion rates were investigated from the glabrous (volar) and non-glabrous hand surfaces during psychogenic (mental arithmetic) and thermogenic stimuli (mild hyperthermia). It was hypothesised that these treatments would activate glands from both skin surfaces, with the non-thermal stimulus increasing secretion rates primarily by recruiting more sweat glands. Ten healthy men participated in two seated, resting trials in temperate conditions (25-26°C). Trials commenced under normothermic conditions during which the first psychogenic stress was applied. That was followed by passive heating (0.5°C mean body temperature elevation) and thermal clamping, with a second cognitive challenge then applied. Sudomotor activity was evaluated from both hands, with colourimetry used to identify activated sweat glands, skin conductance to determine the onset of precursor sweating and ventilated sweat capsules to measure rates of discharged sweating. From glandular activation and sweat rate data, sweat-gland outputs were derived. These psychogenic and thermogenic stimuli activated sweat glands from both the glabrous and non-glabrous skin surfaces, with the former dominating at the glabrous skin and the latter at the non-glabrous surface. Indeed, those stimuli individually accounted for ~90% of the site-specific maximal number of activated sweat glands observed when both stimuli were simultaneously applied. During the normothermic psychological stimulation, sweating from the glabrous surface was elevated via a 185% increase in the number of activated glands within the first 60s. The hypothetical mechanism for this response may involve the serial activation of additional eccrine sweat glands during the progressive evolution of psychogenic sweating.


[Surgical care rendered to the wounded in the antiterrorist operations on the Northern Caucasus: premedical and initial medical care in the combat zone (Report II)].
The analysis of organization and contents of the first aid, premedical and initial medical care rendered to the wounded in the armed conflicts on the Northern Caucasus (1994-1996, 1999-2002) was conducted. It was established that the first aid was rendered to the most casualties who needed it (65% in the first conflict and 79% in the second conflict). The mean terms of rendering the first aid in the second conflict as compared with the conflict of 1994-1996 were decreased from 29 +/- 2 min to 18 +/- min. The role of premedical care was minimal in both conflicts: it was rendered to 3% casualties only. The premedical care was rendered in those cases when the first aid appeared to be ineffective, had obvious defects or in the delay of further evacuation of the wounded. The initial medical care became the central type or pre-hospital care in the combat zone. It was rendered to 56% casualties in the first conflict and to 59% in the second conflict. The mean terms of initial medical care rendered in the second armed conflict were 1.5 +/- 0.2 h. They have considerably decreased as compare with the first conflict (2.5 +/- 0.4 h). The introduction of the physicians with initial surgery and intensive care training in the staffs of regimental medical companies was resulted in significant improvement of initial medical care quality. It provided the adequate preparedness of the wounded for aeromedical evacuation to multipurpose military hospitals of the first level.


Factors which influence synergism by neomycin and oxytetracycline.
Six strains of enteropathogenic gram-negative bacteria were tested for susceptibility to neomycin or oxytetracycline alone and combined in fixed ratios. The minimal inhibitory concentration for the combination was less than one-half of that expected if the antibiotic activities were simply additive. Neomycin alone was more effective against bacteria multiplying in the presence of abundant oxygen, whereas oxytetracycline alone was more effective against bacteria multiplying in relatively anaerobic environments; when combined, the antibiotics complemented each other by their opposing optima for activity. Oxygen concentration, pH, and neomycin activity are related, and the depression of acid production by oxytetracycline is believed to be partially responsible for the synergistic activity of this pair of antibiotics.


Public sector primary care of diabetics--a record review of quality of care in Cape Town.
To evaluate the quality of health care received by diabetics. External audit by means of retrospective record review. SITE: Ambulatory outpatient diabetes clinics at community health centres in black areas of Cape Town. A stratified random sample (520) of all patients who attended any of five health centres during 1991 was reviewed by a clinician who had been trained to do structured record reviews. The response rate was 73.1%. Of all patients reviewed 91% had non-insulin-dependent diabetes mellitus and the remainder insulin-dependent diabetes mellitus; 65% were female and 35.8% were employed. Only 35% attended optimally. Fingerprick blood glucose values were recorded at 98.4% of visits, blood pressure was recorded at 74.1% of all visits and for 97.4% of patients; urine dipstick test results were recorded at 84.6% of visits and for over 99% of patients in 1991, and weight was recorded at 68.8% of visits. In contrast, fundoscopy was recorded for 6% of patients and examination of the feet was performed in 4.7% of patients. Fewer than half (48.9%) of visits resulted in any change in management. Polypharmacy is frequent, with an average of 2.3 non-hypoglycaemic drugs prescribed per visit. Attendance and examination for treatable complications are inadequate. Care is routinised and reactive and there is polypharmacy. Simple but appropriate protocols and matching in-service education are likely to improve the care of and health outcome for diabetics at these sites.


Automated docking of peptides and proteins by using a genetic algorithm combined with a tabu search.
A genetic algorithm (GA) combined with a tabu search (TA) has been applied as a minimization method to rake the appropriate associated sites for some biomolecular systems. In our docking procedure, surface complementarity and energetic complementarity of a ligand with its receptor have been considered separately in a two-stage docking method. The first stage was to find a set of potential associated sites mainly based on surface complementarity using a genetic algorithm combined with a tabu search. This step corresponds with the process of finding the potential binding sites where pharmacophores will bind. In the second stage, several hundreds of GA minimization steps were performed for each associated site derived from the first stage mainly based on the energetic complementarity. After calculations for both of the two stages, we can offer several solutions of associated sites for every complex. In this paper, seven biomolecular systems, including five bound complexes and two unbound complexes, were chosen from the Protein Data Bank (PDB) to test our method. The calculated results were very encouraging-the hybrid minimization algorithm successfully reaches the correct solutions near the best binded modes for these protein complexes. The docking results not only predict the bound complexes very well, but also get a relatively accurate complexed conformation for unbound systems. For the five bound complexes, the results show that surface complementarity is enough to find the precise binding modes, the top solution from the tabu list generally corresponds to the correct binding mode. For the two unbound complexes, due to the conformational changes upon binding, it seems more difficult to get their correct binding conformations. The predicted results show that the correct binding mode also corresponds to a relatively large surface complementarity score. In these two test cases, the correct solution can be found in the top several solutions from the tabu list. For unbound complexes, the interaction energy from energetic complementarity is very important, it can be used to filter these solutions from the surface complementarity. After the evaluation of the energetic complementarity, the conformations and orientations close to the crystallographically determined structures are resolved. In most cases, the smallest root mean square distance (r.m.s.d.) from the GA combined with TA solutions is in a relatively small region. Our program of automatic docking is really a universal one among the procedures used for the theoretical study of molecular recognition.


[Dysphagia secondary to lingual thyroid].
Lingual thyroid is a rare developmental anomaly originating from aberrant embryogenesis during descent of the gland from its site of origin, the foramen caecum, to its eutopic location. We present the case of a 30-year-old female with a history of dysphagia and pharyngeal foreign body sensation over the past 12 months, associated with hypothyroidism. Diagnostic and therapeutic approaches are discussed. Diagnosis of lingual thyroid was made and transoral thyroidectomy was performed as procedure-of-choice. Microscopic analysis revealed normal thyroid tissue with abundant colloid. The patient had an uneventful recovery and was discharged 2 days after surgery. Gamma-gram with Tc99m was scheduled for postoperative follow-up. Transoral lingual thyroidectomy followed by life-long hormonal therapy is the appropiate approach for patients with severe symptoms due to lingual thyroid hypertrophy associated with hypothyroidism.


Incidence of multiple sclerosis in the general population in the Netherlands, 1996-2008.
We estimated the multiple sclerosis (MS) incidence in the Netherlands for better active monitoring of potential vaccine safety signals. A retrospective cohort study (1996-2008) was conducted using a population-based general practice research database containing electronic medical records. Additional information was collected to validate incident probable cases. In the source population (648,656 persons), 146 incident probable MS cases were identified. Overall incidence rate was 6.3/100,000 person years (py; 95% CI, 5.2-7.2). In the subgroup in which MS could be fully validated, the incidence increased from 4/100,000 py (95% CI, 3-5) in 1996-2004 to 9/100,000 py in 2007/8 (95% CI, 6-16). This increase was highest among women, but not statistically significantly different by gender. The median lag time between first recorded symptoms and MS diagnosis decreased from 32 months (<1998) to 2 months (>2005). MS is rare in the Netherlands. In recent years, there was a slight increase in the incidence especially among women during the fertile age. This increase coincided with a decrease in lag time between symptoms and diagnosis, both for men and women. This trend should be taken into account in the interpretation of MS cases occurring in a population where new vaccinations will be introduced shortly.


Production of collagen micro- and nanofibers for potential drug-carrier systems.
Two different nano- and micro-collagen fiber production methods are introduced and discussed. First one is the electrospinning method, that is very common technique to produce nanofibers from different polymeric solutions and recently collagen solutions are employed to produce nanofibers for different biomedical applications. This technique is extremely versatile method to produce nanofibers in a relatively short time, easy to control the fiber diameter and orientation with small pore sizes and a high surface area. The second method is self-assembly of collagen micro-fibers by co-extrusion method. The collagen fibers are obtained without any cross-linker, by using mainly ionic interactions. We demonstrated that self-assembled collagen fibers have well preserved their native structure (0.90 PP-II fraction), when compared with electrospun collagen fibers (0.38 PP-II fraction). However, it was only possible to produce collagen fibers with nanodimensions by using electrospinning method.


Dialysis in the elderly patient: a challenge of the XXI century--narrative review.
With the increase in life expectancy, the improvement of therapeutic arsenal, knowledge and control of chronic degenerative diseases, the world population has reached older age groups. As advanced age is a risk factor for chronic kidney disease (CKD), along with the bonus of increased survival, today we are experiencing the greatest burden of progressive incidence of elderly patients on renal replacement therapy (RRT). Dialysis in elderly patients, which for three decades was considered out of question, today is a routine for nephrologists, who face the challenge of providing care to elderly patients with CKD stage 5 with dialysis indication. In fact, what we see nowadays are dialysis incidents elderly patients as the fastest growing group on RRT. Although without reaching a consensus, it seems indisputable that for elderly patients with CKD, the most important is the quality of life. In this paper we discuss the dialysis in the elderly patient.


Leptospirosis in sugarcane plantation and fishing communities in Kagera northwestern Tanzania.
Leptospirosis is a bacterial zoonotic disease of worldwide importance, though relatively neglected in many African countries including sub Saharan Africa that is among areas with high burden of this disease. The disease is often mistaken for other febrile illnesses such as dengue, malaria, rickettsioses and enteric fever. Leptospirosis is an occupational disease likely to affect people working in environments prone to infestation with rodents which are the primary reservoir hosts of this disease. Some of the populations at risk include: sugarcane plantation workers, wetland farmers, fishermen and abattoir workers. In this study we investigated the prevalence of antibodies against Leptospira among sugarcane plantation and factory workers, fishing communities as well as among rodents and shrews in domestic and peridomestic environments within the study areas. The study was conducted in Kagera region, northwestern Tanzania and it involved sugarcane plantation workers (cutters and weeders), sugar factory workers and the fishing community at Kagera Sugar Company in Missenyi district and Musira island in Lake Victoria, Kagera, respectively. Blood was collected from consenting human adults, and from rodents and shrews (insectivores) captured live using Sherman traps. Serological detection of leptospiral antibodies in blood serum was carried out by the microscopic agglutination test (MAT). A total of 455 participants were recruited from the sugarcane plantation (n = 401) and fishing community (n = 54) while 31 rodents and shrews were captured. The overall prevalence of antibodies against Leptospira in human was 15.8%. Sugarcane cutters had higher seroprevalence than other sugar factory workers. Prevalent antibodies against Leptospira serovars in humans were against serovars Lora (6.8%), Sokoine (5.3%), Pomona (2.4%), Hebdomadis (1.1%) and Kenya (0.2%). Detected leptospiral serovars in reservoir hosts were Sokoine (12.5%) and Grippotyphosa (4.2%). Serovar Sokoine was detected both in humans and small mammals. Leptospirosis is a public health threat affecting populations at risk, such as sugarcane plantation workers and fishing communities. Public awareness targeting risk occupational groups is much needed for mitigation of leptospirosis in the study areas and other vulnerable populations in Tanzania and elsewhere.


Maternal Immunization and Antenatal Care Situation Analysis (MIACSA) study protocol: a multiregional, cross-sectional analysis of maternal immunization delivery strategies to reduce maternal and neonatal morbidity and mortality.
Maternal immunization (MI) with tetanus toxoid containing vaccine, is a safe and cost-effective way of preventing neonatal tetanus. Given the prospect of introducing new maternal vaccines in the near future, it is essential to identify and understand current policies, practices and unmet needs for introducing and/or scaling up MI in low-income and middle-income countries (LMICs). The Maternal Immunization and Antenatal Care Situation Analysis (MIACSA) is a mixed methods, cross-sectional study that will collect data in four phases: (1) a review of global databases for selected health indicators in 136 LMICs; (2) a structured online survey directed at Maternal, Newborn and Child Health and Expanded Programme on Immunization focal points in all 136 LMICs; (3) semistructured telephone interviews of 30 selected LMICs and (4) 10 week-long country visits, including key informant interviews, health facility visits and focus group discussions. The principal analyses will assess correlations between the various aspects of MI delivery strategies and proxy measures of health systems performance related to vaccine-preventable disease control. The primary outcome will be a typology of existing MI delivery models, and secondary outcomes will include country profiles of child and maternal health indicators, and a MI gaps and needs analysis. The protocol was approved by the WHO Ethics Review Committee (ERC.0002908). The results will be made available in a project report and submitted for publication in peer-reviewed journals that will be shared broadly among global health decision-makers, researchers, product developers and country-level stakeholders.


Lytic Cell Death in Specific Microglial Subsets Is Required for Preventing Atypical Behavior in Mice.
Microglial cells are known to contribute to brain development and behaviors, but the mechanisms behind such functions are not fully understood. Here, we show that mice deficient in inflammasome regulators, including caspase-1 (Casp1), NLR family pyrin domain containing 3 (Nlrp3), IL-1 receptor (Il-1r), and gasdermin D (Gsdmd), exhibit behavior abnormalities characterized by hyperactivity and low anxiety levels. Furthermore, we found that expression of Casp1 in CX3CR1+ myeloid cells, which includes microglia, is required for preventing these abnormal behaviors. Through tissue clearing and 3D imaging, we discovered that small numbers of Cx3cr1-GFP+ fetal microglial cells formed clusters and underwent lytic cell death in the primitive thalamus and striatum between embryonic day (E)12.5 and E14.5. This lytic cell death was diminished in Casp1-deficient mice. Further analysis of the microglial clusters showed the presence of Pax6+ neural progenitor cells (NPCs); thus, we hypothesized that microglial lytic cell death is important for proper neuronal development. Indeed, increased numbers of neurons were observed in the thalamic subset in adult Casp1-/- brains. Finally, injection of drug inhibitors of NLRP3 and CASP1 into wild-type (WT) pregnant mice from E12.5 to E14.5, the period when lytic cell death was detected, was sufficient to induce atypical behaviors in offspring. Taken together, our data suggests that the inflammasome cascade in microglia is important for regulating neuronal development and normal behaviors, and that genetic or pharmacological inhibition of this pathway can induce atypical behaviors in mice.


Large-Scale Networks for Auditory Sensory Gating in the Awake Mouse.
The amplitude of the brain response to a repeated auditory stimulus is diminished as compared to the response to the first tone (T1) for interstimulus intervals (ISI) lasting up to hundreds of milliseconds. This adaptation process, called auditory sensory gating (ASG), is altered in various psychiatric diseases including schizophrenia and is classically studied by focusing on early evoked cortical responses to the second tone (T2) using 500-ms ISI. However, mechanisms underlying ASG are still not well-understood. We investigated ASG in awake mice from the brainstem to cortex at variable ISIs (125-2000 ms) using high-density EEG and intracerebral recordings. While ASG decreases at longer ISIs, it is still present at durations (500-2000 ms) far beyond the time during which brain responses to T1 could still be detected. T1 induces a sequence of specific stable scalp EEG topographies that correspond to the successive activation of distinct neural networks lasting about 350 ms. These brain states remain unaltered if T2 is presented during this period, although T2 is processed by the brain, suggesting that ongoing networks of brain activity are active for longer than early evoked-potentials and are not overwritten by an upcoming new stimulus. Intracerebral recordings demonstrate that ASG is already present at the level of ventral cochlear nucleus (vCN) and inferior colliculus and is amplified across the hierarchy in bottom-up direction. This study uncovers the extended stability of sensory-evoked brain states and long duration of ASG, and sheds light on generators of ASG and possible interactions between bottom-up and top-down mechanisms.


Underage sales signage in vape shops: Comparison of stores near and far from California colleges.
Objective: Two-thirds of U.S. colleges are near vape shops, where higher rates of underage sales exist. This study examined vape shop compliance with state-mandated age-of-sale signs, the presence of age-of-entry signs and the tobacco industry's "We Card" sign. Participants: Random sample of 614 California vape shops, stratified by distance to community colleges or 4-year universities/colleges; visited June-August, 2019. Methods: Logistic regressions examined whether signage varied by distance to colleges and whether stores sold other tobacco products (OTP). Results: Compliance with the state-mandated age-of-sale sign was 69.4%; vape-only stores were less compliant than vape + OTP (AOR = 0.39, 95% CI = 0.22,0.70). Age-of-entry signs were more common in vape-only (AOR = 1.87, 95% CI = 1.07,3.28) than vape + OTP stores. However, this difference was greater for vape-only stores near community colleges and attenuated for vape-only stores near 4-year universities/colleges. Conclusion: Improved enforcement and retailer education regarding age-of-sale signage are needed, particularly near colleges where greater potential for underage sales presumably exists.


Psychopathology in first-episode schizophrenia and antibodies to Toxoplasma gondii.
Environmental factors such as infectious agents may contribute to the psychopathology and aetiology of schizophrenia. Toxoplasma gondii (TG) is a candidate infectious agent as it is known to replicate within the human central nervous system and to alter behaviour in experimental animals. The relationship between antibodies to TG and psychopathological symptoms was examined in 34 first-episode patients with schizophrenia. Results of regression analyses revealed that symptoms on admission, predictors of outcome, age and family history of psychiatric disease influenced the levels of antibodies to TG. These results indicate that TG infections may play a role in the clinical manifestation of psychopathology in a subgroup of patients with schizophrenia.


Diagnostic performance of bile duct brush cytology with risk of malignancy of standardized categories in the wake of World Health Organization Reporting System for Pancreaticobiliary Cytopathology: An updated systematic review and meta-analysis.
The WHO Reporting System for Pancreaticobiliary Cytopathology revised the Papanicolaou Society of Cytopathology guidelines in alignment with the WHO classification of digestive system tumors, 5th edition. The current systematic review and meta-analysis have been conducted to accurately assess the performance of bile duct brush cytology and report the risk of malignancy (ROM) of each standard category by following the guidelines of diagnostic test accuracy meta-analysis. Medline/ Pubmed and Cochrane databases were searched till 8th June 2023 with a strategy that included target site (pancreaticobiliary and related terms), diagnostic method (bile duct brushing and related terms), and keywords for diagnostic performance (for Cochrane database). Inclusion criteria included studies that have assessed bile duct cytology (BDC) for pancreaticobiliary duct stricture with a sample size of over 50, provided cytological diagnoses similar to the WHO system with details to deduce true positives, true negatives, false positives, and false negatives through subsequent final diagnoses (Benign vs. Malignant). The exclusion criteria were the fewer sample size, assessment through other cytological categories, limited data, and clinical setting. Two authors independently reviewed the result of the search strategy. The quality of the selected articles was assessed by the QUADAS-2 tool. Bivariate random-effects model was used to get the pooled sensitivity and specificity. Heterogeneity across studies was assessed using I-squared statistics, and potential sources were found using meta-regression. Pooled and a range of ROM in each category was analyzed. Thirteen studies were included with 4398 bile duct brushings. The pooled sensitivity is 0.437 (95% CI: 0.371-0.504), and the pooled specificity is 0.972 (95% CI: 0.943-0.987). The ROM in various categories are as follows: inadequate/non-diagnostic: 23%-100% (pooled- 50.15%), benign/negative for malignancy: 22%-70% (38%), atypical: 0%-95% (66%), suspicious for malignancy: 74%-100% (89%), malignant: 91% to 100% (98%). Even with standard cytological categories, the sensitivity of BDC remains low. The review has analyzed and discussed potential causes of heterogeneity that will be helpful for future diagnostic studies.


Mactra veneriformis, an intertidal clam, as a new second intermediate host for Acanthoparyphium marilae (Digenea: Echinostomatidae).
Metacercariae of Acanthoparyphium marilae Yamaguti, 1934 (Digenea: Echinostomatidae) were discovered in an intertidal clam, Mactra veneriformis, in a southwestern coastal area of the Republic of Korea. A total of 128 metacercariae were detected from 10 clams examined. They were round, 320 microm in average diameter, with 23 collar spines. They were fed experimentally to chicks, and 10 days later adult flukes were obtained. The adults were morphologically characterized by the head collar with a single row of 23 dorsally uninterrupted spines, without special end group spines, a round ventral sucker, 2 round and tandem testes, and vitellaria extending at lateral fields from the posterior extremity not beyond the middle level of the posterior testis. The most characteristic feature of this species was the limited distribution of vitellaria, which differs from Acanthoparyphium tyosenense Yamaguti, 1939, the metacercariae of which are encysted in the same mollusk species. This is the first report in which the metacercariae of this species were detected, and the intertidal bivalve, M. veneriformis, has been identified as a second intermediate host for A. marilae.


Alcohol drinking, cigarette smoking, and risk of colorectal adenomatous and hyperplastic polyps.
The authors evaluated alcohol drinking and cigarette smoking in relation to risk of colorectal polyps in a Nashville, Tennessee, colonoscopy-based case-control study. In 2003-2005, cases with adenomatous polyps only (n = 639), hyperplastic polyps only (n = 294), and both types of polyps (n = 235) were compared with 1,773 polyp-free controls. Unordered polytomous logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals. Consumption of at least five alcoholic drinks per week was not strongly associated with development of polyps. Odds ratios for all polyp types were increased for dose, duration, and pack-years of cigarette smoking and were stronger for hyperplastic polyps than for adenoma. Compared with never smoking, dose-response relations were particularly strong for current smoking and duration; for > or =35 years of smoking, odds ratios were 1.9 (95% confidence interval (CI): 1.4, 2.5) for adenomatous polyps only, 5.0 (95% CI: 3.3, 7.3) for hyperplastic polyps only, and 6.9 (95% CI: 4.4, 11.1) for both types of polyps. Compared with current smoking, time since cessation was associated with substantially reduced odds; for > or =20 years since quitting, odds ratios were 0.4 (95% CI: 0.3, 0.6) for adenoma only, 0.2 (95% CI: 0.1, 0.3) for hyperplastic polyps only, and 0.2 (95% CI: 0.2, 0.4) for both polyp types. These findings support the adverse role of cigarette smoking in colorectal tumorigenesis and suggest that quitting smoking may substantially reduce the risk of colorectal polyps.


A transiently chaotic neural-network implementation of the CDMA multiuser detector.
The complex dynamics of the chaotic neural networks makes it possible for them to escape from local minimum of the simple gradient descent neurodynamics. In this letter we use a transiently chaotic neural network to detect the CDMA multiuser signals and hence obtain an implementation scheme of the CDMA multiuser detector (TCNN-MD). Computer simulation results show that the proposed detector is clearly superior to Hopfield neural-network-based detector.


Responses of flavonoid profile and associated gene expression to solar blue and UV radiation in two accessions of Vicia faba L. from contrasting UV environments.
Blue light and UV radiation shape a plant's morphology and development, but accession-dependent responses under natural conditions are unclear. Here we tested the hypothesis that two faba bean (Vicia faba L.) accessions adapted to different latitudes and altitudes vary in their responses to solar blue and UV light. We measured growth, physiological traits, phenolic profiles and expression of associated genes in a factorial experiment combining two accessions (Aurora, a Swedish cultivar adapted to high latitude and low altitude; ILB938, from the Andean region of Colombia and Ecuador, adapted to low latitude and high altitude) and four filter treatments created with plastic sheets: 1. transparent as control; 2. attenuated short UV (290-350 nm); 3. attenuated UV (290-400 nm); 4. attenuated blue and UV light. In both accessions, the exclusion of blue and UV light increased plant height and leaf area, and decreased transcript abundance of ELONGATED HYPOCOTYL 5 (HY5) and TYROSINE AMINOTRANSFERASE 3 (TAT3). Blue light and short UV induced the accumulation of epidermal and whole-leaf flavonoids, mainly quercetins, and the responses in the two accessions were through different glycosides. Filter treatments did not affect kaempferol concentration, but there were more tri-glycosides in Aurora and di-glycosides in ILB938. Furthermore, fewer quercetin glycosides were identified in ILB938. The transcript abundance was consistently higher in Aurora than in ILB938 for all seven investigated genes: HY5, TAT3, CHALCONE SYNTHASE (CHS), CHALCONE ISOMERASE (CHI), DON-GLUCOSYLTRANSFERASE 1 (DOGT1), ABA INSENSITIVE 2 (ABI2), AUXIN-INDUCIBLE 2-27 (IAA5). The two largest differences in transcript abundance between the two accessions across treatments were 132-fold in CHS and 30-fold in DOGT1 which may explain the accession-dependent glycosylation patterns. Our findings suggest that agronomic selection for adaptation to high altitude may favour phenotypes with particular adaptations to the light environment, including solar UV and blue light.


Integrating Nutrition Interventions into an Existing Maternal, Neonatal, and Child Health Program Increased Maternal Dietary Diversity, Micronutrient Intake, and Exclusive Breastfeeding Practices in Bangladesh: Results of a Cluster-Randomized Program Evaluation.
Background: Maternal undernutrition is a major concern globally, contributing to poor birth outcomes. Limited evidence exists on delivering multiple interventions for maternal nutrition simultaneously. Alive & Thrive addressed this gap by integrating nutrition-focused interpersonal counseling, community mobilization, distribution of free micronutrient supplements, and weight-gain monitoring through an existing Maternal, Neonatal, and Child Health (MNCH) program in Bangladesh.Objectives: We evaluated the effect of providing nutrition-focused MNCH compared with standard MNCH (antenatal care with standard nutrition counseling) on coverage of nutrition interventions, maternal dietary diversity, micronutrient supplement intake, and early breastfeeding practices.Methods: We used a cluster-randomized design with cross-sectional surveys at baseline (2015) and endline (2016) (n ∼ 300 and 1000 pregnant or recently delivered women, respectively, per survey round). We derived difference-in-difference effect estimates, adjusted for geographic clustering and infant age and sex.Results: Coverage of interpersonal counseling was high; >90% of women in the nutrition-focused MNCH group were visited at home by health workers for maternal nutrition and breastfeeding counseling. The coverage of community mobilization activities was ∼50%. Improvements were significantly greater in the nutrition-focused MNCH group than in the standard MNCH group for consumption of iron and folic acid [effect: 9.8 percentage points (pp); 46 tablets] and calcium supplements (effect: 12.8 pp; 50 tablets). Significant impacts were observed for the number of food groups consumed (effect: 1.6 food groups), percentage of women who consumed ≥5 food groups/d (effect: 30.0 pp), and daily intakes of several micronutrients. A significant impact was also observed for exclusive breastfeeding (EBF; effect: 31 pp) but not for early initiation of breastfeeding.Conclusions: Addressing nutrition during pregnancy by delivering interpersonal counseling and community mobilization, providing free supplements, and ensuring weight-gain monitoring through an existing MNCH program improved maternal dietary diversity, micronutrient supplement consumption, and EBF practices. This trial was registered at clinicaltrials.gov as NCT02745249.


Effects of gamma-terpinene on lipid concentrations in serum using Triton WR1339-treated rats.
We studied lipid metabolism to evaluate the effects of gamma-terpinene on suppression of increases in serum lipid concentrations using Triton WR1339-treated rats. At 6 hr after Triton WR1339 injection, the total cholesterol and triglyceride concentrations in the gamma-terpinene group underwent statistically significant decreases (18.3 and 30.3%, respectively) compared with those of the Triton-treated group.


Survival, migration, and differentiation of Sox1-GFP embryonic stem cells in coculture with an auditory brainstem slice preparation.
The poor regeneration capability of the mammalian hearing organ has initiated different approaches to enhance its functionality after injury. To evaluate a potential neuronal repair paradigm in the inner ear and cochlear nerve we have previously used embryonic neuronal tissue and stem cells for implantation in vivo and in vitro. At present, we have used in vitro techniques to study the survival and differentiation of Sox1-green fluorescent protein (GFP) mouse embryonic stem (ES) cells as a monoculture or as a coculture with rat auditory brainstem slices. For the coculture, 300 microm-thick brainstem slices encompassing the cochlear nucleus and cochlear nerve were prepared from postnatal SD rats. The slices were propagated using the membrane interface method and the cochlear nuclei were prelabeled with DiI. After some days in culture a suspension of Sox1 cells was deposited next to the brainstem slice. Following deposition Sox1 cells migrated toward the brainstem and onto the cochlear nucleus. GFP was not detectable in undifferentiated ES cells but became evident during neural differentiation. Up to 2 weeks after transplantation the cocultures were fixed. The undifferentiated cells were evaluated with antibodies against progenitor cells whereas the differentiated cells were determined with neuronal and glial markers. The morphological and immunohistochemical data indicated that Sox1 cells in monoculture differentiated into a higher percentage of glial cells than neurons. However, when a coculture was used a significantly lower percentage of Sox1 cells differentiated into glial cells. The results demonstrate that a coculture of Sox1 cells and auditory brainstem present a useful model to study stem cell differentiation.


[Arterial stiffness in patients with chronic obstructive lung disease in the presence and absence of ischemic heart disease].
Aim of the study was assessment of arterial stiffness in patients with chronic obstructive lung disease (COPD) with or without ischemic heart disease (IHD). We included in this open study 130 COPD patients older than 40 years (mean age 60.2+/-8.3 years). Patients with clinical signs of exacerbation of other severe chronic diseases were not included. Control group comprised 18 practically healthy volunteers older than 50years (mean age 56.9+/-7.2 years). Tensioclinic arteriograph was used for evaluation of arterial wall stiffness. The study revealed increase of pulse wave propagation velocity associated with elevation of augmentation indexes in COPD patients both with and without IHD as well as in patients with different degrees of 10-year risk of cardiovascular death. These changes can be considered as systemic manifestations of COPD possibly underlining interrelationships between COPD and cardiovascular diseases.


Forskolin refractoriness. Exposure to the diterpene alters guanine nucleotide-dependent adenylate cyclase and calcium-uptake activity of cells cultured from the rat aorta.
Cells with the morphological properties of endothelial cells were cultured from the rat aorta. The cultured cells accumulated 45Ca2+ from the medium in a manner which was stimulated by forskolin and by 8-bromo-cyclic AMP. Pretreating the cultures for 20 h with forskolin diminished forskolin-dependent Ca2+-uptake activity. Adenylate cyclase activity of cultured cell homogenates was stimulated by guanosine 5'-[beta, gamma-imido]triphosphate (p[NH]ppG) and forskolin, and by isoprenaline in the presence, but not in the absence, of guanine nucleotide. p[NH]ppG increased forskolin sensitivity and caused a leftward shift in the forskolin dose-response curve. Pretreating the cultured cells with forskolin for 20 h, conditions that decreased forskolin-dependent Ca2+ uptake, increased basal and guanine nucleotide-dependent adenylate cyclase activity, but not forskolin-dependent activity determined in the absence of p[NH]ppG. Forskolin pretreatment diminished p[NH]ppG's capacity to increase forskolin sensitivity, but did not have a significant effect on either the sensitivity of adenylate cyclase to p[NH]ppG or its responsiveness to isoprenaline. These results suggest that the Ca2+-uptake mechanism is cyclic AMP-dependent and that guanine nucleotides mediated forskolin-dependent cyclic AMP production by the intact cells. In addition, there may be different guanine nucleotide requirements for hormone-receptor coupling and forskolin activation.


Minimal truncation of the c-myb gene product in rapid-onset B-cell lymphoma.
Oncogenic activation of c-myb by insertional mutagenesis has been implicated in rapid-onset B-cell lymphomas induced by the nonacute avian leukosis virus EU-8. In these tumors, proviruses are integrated either upstream of the c-myb coding region or within the first intron of c-myb. Tumors with either type of integration contained identical chimeric mRNAs in which the viral 5' splice site was juxtaposed to the 3' splice site of c-myb exon 2 and myb exon 1 was eliminated. Both classes of integrations generated truncated Myb proteins that were indistinguishable by Western analysis. In contrast to most other examples of c-myb activation, the truncation consisted of only 20 N-terminal amino acids and did not disrupt either the DNA binding domain near the N terminus or the negative regulatory domain near the C terminus of Myb. The significance of the 20-amino-acid Myb truncation to tumorigenesis was tested by infection of chicken embryos with retroviral vectors expressing different myb gene products. While virus expressing either wild-type c-myb or c-myb mutated at the N-terminal casein kinase II sites was only weakly oncogenic at 10 weeks, the minimally truncated myb virus induced a high incidence of rapid-onset tumors, including B-cell lymphomas, sarcomas, and adenocarcinomas.


Differential induction of cytotoxicity and apoptosis by influenza virus strains of differing virulence.
Two influenza viruses of differing virulence, clone 7a (virulent for humans and ferrets) and A/Fiji (attenuated for both species), induced differential levels of cytotoxicity (as measured by release of lactate dehydrogenase from cells) and apoptosis (as determined by altered nuclear morphology or flow cytometry) in MDCK and U-937 cells. Clone 7a induced more apoptosis and cytotoxicity than A/Fiji, despite the fact that its infectious virus yields were similar to or less than those for A/Fiji. This indicates a greater capacity of clone 7a to induce the two phenomena. Nevertheless the replication process was clearly essential, since UV-irradiated virus induced little or no apoptosis, and apoptosis occurred as a late event post-infection. The possible relevance of these findings to destruction of host cells by influenza virus in vivo is discussed.


Circulating microRNA-23b as a new biomarker for rheumatoid arthritis.
MicroRNA-23b (miR-23b) is associated with inflammation and autoimmune diseases. This study evaluated miR-23b expression and assessed its potential as a biomarker of disease activity for rheumatoid arthritis (RA). Differential expression of microRNAs was determined by miRNA microarray analysis in fibroblast-like synoviocytes (FLSs) from four trauma patients as healthy controls (HCs) and eight RA patients. The microarray results showed elevated expression of miR-23b in FLSs from RA patients and this finding was corroborated by real-time quantitative polymerase chain reaction (RT-qPCR) and in situ hybridization using synovial tissues (STs). Furthermore, we found miR-23b levels in plasma of RA patients were significantly higher than in HCs, and plasma miR-23b levels positively correlated with the erythrocyte sedimentation rate (ESR), hypersensitive C-reactive protein (hs-CRP), C-reactive protein (CRP), DAS28, and platelet (PLT) count (P < 0.05). MiR-23b levels in plasma inversely correlated with the levels of hemoglobin (Hb), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (P < 0.05), but not with rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibodies (ACPA) (P > 0.05). Moreover, patients with anorexia showed higher levels of miR-23b in plasma than those without anorexia. Similar results were observed with fatigue. Appropriate treatment for RA not only ameliorated the disease condition but also reversed the elevated plasma miR-23b level remarkably. These results suggest that circulating miR-23b may be a promising biomarker for RA disease activity.


Molecular cloning and expression of ovarian cathepsin D in seabream, Sparus aurata.
In marine fish producing pelagic eggs, the acquirement of buoyancy by the eggs through the hydration process is a key event of reproduction; moreover, the yolk proteolysis, which leads to buoyancy, seems to affect the fertility and survival of the spawned eggs. Recently we demonstrated that cathepsin D is the aspartic protease responsible for this intraoocytic processing of vitellogenin into yolk proteins. In the present study, we isolated, cloned, and sequenced the cDNA encoding cathepsin D and studied expression of the message by Northern blotting and whole-mount in situ hybridization. The full-length seabream cathepsin D cDNA is 1837 base pairs long, encoding a protein of 400 amino acids (aa) consisting of a signal peptide of 19 aa, a prosequence of 44 aa, and a mature peptide of 336 aa. An absolute sequence conservation at the aspartyl residues (+33 and +221) was found, and there are three potential N-glycosylation sites at +70, aa +189, and aa +274. The aa sequence of seabream cathepsin D reveals a high degree of sequence similarity with cathepsin D mRNAs from other organisms (73% sequence homology to mouse and rat, 72% to human and trout, 69% to chicken, 66% to pig, and 65% to Xenopus). The cathepsin D mRNA in floating eggs was present as a single band that was approximately 1.9 kilobases (kb) in size, while in the sinking eggs there were several fast-migrating bands (size range 1.3-0.2 kb). Whole-mount hybridization was used to investigate transcription of cathepsin D in the developing embryo; during the hatching period, cathepsin D mRNA-positive cells were distributed in a wide region between the trunk and the tail, and in the ventral region over the yolk ball. The highest levels of cathepsin D enzymatic activity were found in the sinking eggs and during the hatching period of embryonic development. These data suggest that cathepsin D can be considered a possible marker for egg quality.


The introduction history of invasive garden ants in Europe: integrating genetic, chemical and behavioural approaches.
The invasive garden ant, Lasius neglectus, is the most recently detected pest ant and the first known invasive ant able to become established and thrive in the temperate regions of Eurasia. In this study, we aim to reconstruct the invasion history of this ant in Europe analysing 14 populations with three complementary approaches: genetic microsatellite analysis, chemical analysis of cuticular hydrocarbon profiles and behavioural observations of aggression behaviour. We evaluate the relative informative power of the three methodological approaches and estimate both the number of independent introduction events from a yet unknown native range somewhere in the Black Sea area, and the invasive potential of the existing introduced populations. Three clusters of genetically similar populations were detected, and all but one population had a similar chemical profile. Aggression between populations could be predicted from their genetic and chemical distance, and two major clusters of non-aggressive groups of populations were found. However, populations of L. neglectus did not separate into clear supercolonial associations, as is typical for other invasive ants. The three methodological approaches gave consistent and complementary results. All joint evidence supports the inference that the 14 introduced populations of L. neglectus in Europe likely arose from only very few independent introductions from the native range, and that new infestations were typically started through introductions from other invasive populations. This indicates that existing introduced populations have a very high invasive potential when the ants are inadvertently spread by human transport.


Plant adaptation to climate change.
Plants are vital to human health and well-being, as well as helping to protect the environment against the negative impacts of climate change. They are an essential part of the 'One Health' strategy that seeks to balance and optimize the health of people, animals and the environment. Crucially, plants are central to nature-based solutions to climate mitigation, not least because soil carbon storage is an attractive strategy for mitigating greenhouse gas emissions and the associated climate change. Agriculture depends on genetically pure, high-quality seeds that are free from pests and pathogens and contain a required degree of genetic purity. This themed collection addresses key questions in the field encompassing the biochemical mechanisms that underlie plant responses and adaptations to a changing climate. This collection encompasses an analysis of the biochemistry and molecular mechanisms underpinning crop and forest resilience, together with considerations of plant adaptations to climate change-associated stresses, including drought, floods and heatwaves, and the increased threats posed by pathogens and pests.


Resonant 2-photon ionization study of the conformation and the binding of water molecules to 2-phenylethanethiol (PhCH2CH2SH).
The structures of 2-phenylethanethiol (PET, PhCH(2)CH(2)SH) and its 1:1 water clusters have been studied using resonant two-photon ionization spectroscopy including band contour analysis and UV-UV holeburning, combined with extensive ab initio calculations on ground and excited states. The most populated conformer, labeled Ggpi, has a gauche arrangement about the SCCC and HSCC bonds that permits a stabilizing SH...dpi type of hydrogen bond. The other observed conformer, Ag, is anti with respect to the SCCC bond. In the dominant 1:1 water cluster, a water molecule binds to the Ggpi conformer via an OH...S hydrogen bond and two significant CH...O interactions. There is also evidence for water binding to conformer Ag with a similar arrangement, and for a second Ggpi cluster where water inserts between the SH and the aromatic ring. The additional interactions to the water molecules result in net D(e) binding energies approximately double those resulting from a single thiol-water hydrogen bond. The (1)(pi,pi(*)) excited state lifetimes in the bare molecules are very short because of internal conversion to a dissociative (1)(n,pi(*)) state related to the thiol. In the dominant Gw(1) cluster, the lifetime is significantly increased from <1 to approximately 4 ns. Hydrogen bonding to the thiol, which raises the energy of the dissociative (1)(n,pi(*)) state, accounts for this behavior.


Transcriptional expression study in the central nervous system of rats: what gene should be used as internal control?
A growing number of published articles report the expression of specific genes with different behavior patterns in rats. The levels of messenger ribonucleic acid transcripts are usually analyzed by reverse transcription followed by polymerase chain reaction and quantified after normalization with an internal control or reference gene (housekeeping gene). Nevertheless, housekeeping genes exhibit different expression in the central nervous system, depending on the physiological conditions and the area of the brain to be studied. The choice of a good internal control gene is essential for obtaining reliable results. This study evaluated the expression of three housekeeping genes (beta-actin, cyclophilin A, and ubiquitin C) in different areas of the central nervous system in rats (olfactory bulb, hippocampus, striatum, and prefrontal cortex). Wistar rats (virgin females, n=6) during the diestrum period were used. Total ribonucleic acid was extracted from each region of the brain; the complementary deoxyribonucleic acid was synthesized by reverse transcription and amplified by real-time quantitative polymerase chain reaction using SYBR™ Green and primers specific for each one of the reference genes. The stability of the expression was determined using NormFinder. Beta-actin was the most stable gene in the hippocampus and striatum, while cyclophilin A and ubiquitin C showed greater stability in the prefrontal cortex and the olfactory bulb, respectively. Based on our study, further studies of gene expression using rats as animal models should take into consideration these results when choosing a reliable internal control gene.


Confidence to cook vegetables and the buying habits of Australian households.
Cooking skills are emphasized in nutrition promotion but their distribution among population subgroups and relationship to dietary behavior is researched by few population-based studies. This study examined the relationships between confidence to cook, sociodemographic characteristics, and household vegetable purchasing. This cross-sectional study of 426 randomly selected households in Brisbane, Australia, used a validated questionnaire to assess household vegetable purchasing habits and the confidence to cook of the person who most often prepares food for these households. The mutually adjusted odds ratios (ORs) of lacking confidence to cook were assessed across a range of demographic subgroups using multiple logistic regression models. Similarly, mutually adjusted mean vegetable purchasing scores were calculated using multiple linear regression for different population groups and for respondents with varying confidence levels. Lacking confidence to cook using a variety of techniques was more common among respondents with less education (OR 3.30; 95% confidence interval [CI] 1.01 to 10.75) and was less common among respondents who lived with minors (OR 0.22; 95% CI 0.09 to 0.53) and other adults (OR 0.43; 95% CI 0.24 to 0.78). Lack of confidence to prepare vegetables was associated with being male (OR 2.25; 95% CI 1.24 to 4.08), low education (OR 6.60; 95% CI 2.08 to 20.91), lower household income (OR 2.98; 95% CI 1.02 to 8.72) and living with other adults (OR 0.53; 95% CI 0.29 to 0.98). Households bought a greater variety of vegetables on a regular basis when the main chef was confident to prepare them (difference: 18.60; 95% CI 14.66 to 22.54), older (difference: 8.69; 95% CI 4.92 to 12.47), lived with at least one other adult (difference: 5.47; 95% CI 2.82 to 8.12) or at least one minor (difference: 2.86; 95% CI 0.17 to 5.55). Cooking skills may contribute to socioeconomic dietary differences, and may be a useful strategy for promoting fruit and vegetable consumption, particularly among socioeconomically disadvantaged groups.


Multilingual website and cyberconsultations for oromandibular dystonia.
Oromandibular dystonia is a focal dystonia that manifests as involuntary masticatory and/or tongue muscle contractions. This movement disorder is frequently misdiagnosed as a temporomandibular disorder. Hence, it would be useful to establish a method that makes it possible for patients with the condition to find appropriate medical institutions by themselves. The author produced a website Involuntary movements of the stomatognathic region (https://sites. google.com/site/oromandibulardystoniaenglish/) for patients with oromandibular dystonia, which is available in twenty languages. It has been viewed more than 1,000,000 times by individuals from all over the world. The visitors to the site have completed questionnaires and/or sent images or videos of their involuntary movements over the internet. Cyberconsultations (remote diagnosis) were also performed via Skype™. Approximately 1000 patients with involuntary stomatognathic movements visited our department. Only 12.5% of the patients had previously been diagnosed with or were suspected to have dystonia. The findings of this study suggest that the multilingual website has contributed to increasing awareness of oromandibular dystonia and that the provision of basic telemedicine via the internet can aid the diagnosis and treatment of oromandibular dystonia.


[Responses of auditory neurons of the medulla oblongata of the frog to presentation of tones with sinusoidal amplitude modulation].
The responses of single units in the medullary auditory regions of the frog Rana ridibunda to sinusoidally amplitude-modulated tones of characteristic frequencies were studied. The reproduction of the sound modulation in the discharge frequency of the units was determined from cycle histograms of the discharges locked to the modulation period. In dorsal nucleus units the amplitude modulation was preserved in the discharge modulation over a wide modulation frequency and sound intensity ranges. In many superior olivary neurons an enhancement of small amplitude changes within the range of modulation frequencies 70-150 Hz was observed. The reaction phase was linear-dependent on the modulation frequency. The best enhancement of amplitude changes took place for small modulation indices.


The ICP0 protein of equine herpesvirus 1 is an early protein that independently transactivates expression of all classes of viral promoters.
To assess the role of the equine herpesvirus type 1 (EHV-1) ICP0 protein (EICP0) in gene regulation, a variety of molecular studies on the EICP0 gene and gene products of both the attenuated cell culture-adapted Kentucky A (KyA) strain and the Ab4p strain were conducted. These investigations revealed that (i) the ICP0 open reading frame (ORF) of the KyA virus strain is 1,257 bp in size and would encode a protein of 419 amino acids, and in comparison to the ICP0 gene (ORF63) of the Ab4p strain of 1,596 bp (E. A. Telford, M. S. Watson, K. McBride, and A. J. Davison, Virology 189:304-316, 1992), it has an internal in-frame deletion of 339 bp; (ii) one early transcript of 1.4 kb predicted to encode the EICP0 protein and a late transcript of 1.8 kb are detected in Northern blot analyses using probes containing the EICP0 ORF; (iii) the KyA EICP0 protein (50 kDa) and the Ab4p EICP0 protein (80 kDa) are expressed as several species of early proteins that are first detected at 3 to 4 h postinfection by Western blot analyses of infected-cell polypeptides, using an antiserum generated to a TrpE fusion protein that harbors amino acids 46 to 153 of the EICP0 protein; and (iv) the EICP0 protein of both EHV-1 strains is a potent transactivator of EHV-1 genes. Transient expression assays using a simian virus 40 expression construct of the EICP0 protein of the KyA strain showed that the EICP0 protein independently transactivated chloramphenicol acetyltransferase reporter constructs under the control of the immediate-early promoter (3.9-fold), the early thymidine kinase promoter (95-fold), the late (gamma1) IR5 promoter (85-fold), and the late (gamma2) glycoprotein K promoter (21-fold). The finding that the EICP0 protein of the KyA virus can function as an activator of gene expression indicates that amino acids corresponding to residues 319 to 431 of the Ab4p EICP0 protein are not essential for EICP0 transactivation of EHV-1 promoters.


Cranial Fasciitis: A Systematic Review and Diagnostic Approach to a Pediatric Scalp Mass.
Cranial fasciitis is an uncommon, benign fibroproliferative condition of the scalp or skull that arises in children. Clinically, it manifests as a firm, nontender, subcutaneous, enlarging mass. The purpose of our study was to review the literature on cranial fasciitis to create a diagnostic algorithm using the latest patient at our institution as an example. The authors conducted a systematic review examining all published cases of cranial fasciitis in English literature. The authors then created a diagnostic algorithm to help distinguish cranial fasciitis from other similarly presenting cranial masses. To demonstrate this algorithm, the authors detailed the latest patient with cranial fasciitis at our institution. The authors extracted data from 53 published reports documenting 72 patients of cranial fasciitis. Our patient presented similarly to what was reported in the literature. A 7-week-old boy presented with 2 small parietal scalp masses that were noted shortly after birth. After noncontrast computed tomography imaging, the enlarging masses were resected and found to have eroded the outer cranial vault cortex. Histological analysis revealed cranial fasciitis. The differential diagnosis for an enlarging scalp mass in an infant or child is broad. Cranial fasciitis cannot be diagnosed based on clinical presentation alone. Imaging is usually employed to further characterize lesions after initial examination but histopathological analysis is essential for diagnosis. The locally invasive nature of cranial fasciitis makes it difficult to distinguish from malignant conditions such as sarcomas. However, if the diagnosis of cranial fasciitis is considered early, patients can achieve prompt clinical resolution following simple resection.


No evidence for an association of plasma homocysteine levels and refractive error - Results from the population-based Gutenberg Health Study (GHS).
There is a strong association between severe hyperhomocysteinemia and myopia. Thus we studied the hypothesis that even moderately increased levels of homocysteine (Hcy) might be a potentially treatable risk factor for myopia. The Gutenberg Health Study (GHS) is a population-based, prospective, observational cohort study in Germany, including 15,010 participants aged between 35 and 74 at recruitment. The baseline examination was conducted from 2007-2012. Refraction was measured using autorefraction (HARK 599, Carl Zeiss AG, Jena, Germany). Hcy was measured by an immunoassay. We included only phakic participants without a history of corneal surgery or corneal laser treatment. We used linear regression models to evaluate the potential association between Hcy and refraction at baseline, and between Hcy and change in refraction between baseline and 5-year-follow-up examination. We used generalized estimating equation models to account for the correlation between fellow eyes. We included 13,749 participants, categorized as having no myopia (spherical equivalent > -0.75 D, 65.2%), low myopia (-0.75 D--2.75 D, 21.5%), moderate myopia (-3.00 D- 5.75 D, 9.8%) and high myopia (≤ -6 D, 3.5%). Median Hcy levels were similar in all groups (μmol/l). We observed no association of Hcy with refraction or 5-year change in refraction in the models adjusted for age, sex and socioeconomic status. We found no evidence for an association of Hcy levels and refractive error.


Genetic features of Pseudomonas aeruginosa isolates from cystic fibrosis patients compared with those of isolates from other origins.
In order to improve our understanding of the colonization of the pulmonary tract of cystic fibrosis (CF) patients by Pseudomonas aeruginosa, 162 isolates from five different ecological origins were studied. The genetic features of each isolate were determined by random amplification of polymorphic DNA (RAPD) and by searching for eight virulence genes (six known virulence genes, algD, lasB, toxA, plcH, plcN and exoS, and two genes encoding putative neuraminidases, nan1 and nan2). Five RAPD groups were identified. Most of the CF isolates were distributed equally in three of these groups (RA, RB and RC). The CF isolates in RB were related to isolates from a wide variety of origins. The CF isolates in RA were related to a population composed of 65 % of the non-CF isolates from pulmonary tract infections. RC was mainly composed of CF isolates that were related to 30 % of isolates from plants. All genes except exoS and nan1 were present in all isolates. The exoS and nan1 virulence factor genes were most prevalent in CF isolates. exoS, which encodes exoenzyme S, was present in 94 % of CF isolates but also in 80 % of non-CF isolates from pulmonary tract infections. nan1, which encodes a putative neuraminidase, was found in 82.5 % of the isolates from group RC, which was composed largely of CF isolates. In conclusion, three major genogroups of P. aeruginosa isolates, each of which exhibits peculiar genetic features, are able to colonize CF patients. This may have different consequences on the outcome of pulmonary disease.


Utility of ultrasound in managing acute medical conditions in space: a scoping review.
In long-distance spaceflight, the challenges of communication delays and the impracticality of rapid evacuation necessitate the management of medical emergencies by onboard physicians. Consequently, these physicians must be proficient in tools, such as ultrasound, which has proven itself a strong diagnostic imaging tool in space. Yet, there remains a notable gap in the discourse surrounding its efficacy in handling acute medical scenarios. This scoping review aims to present an updated analysis of the evidence supporting the role of ultrasound in diagnosing acute conditions within microgravity environments. A systematic search was executed across three bibliographic databases: PubMed, EMBASE (Embase.com), and the Web of Science Core Collection. We considered articles published up to February 25, 2023, that highlighted the application of ultrasound in diagnosing acute medical conditions in either microgravity or microgravity-simulated settings. Exclusions were made for review papers, abstracts, and in-vitro studies. After removing duplicates, and filtering papers by pre-determined criteria, a total of 15 articles were identified that discuss the potential use of ultrasound in managing acute medical conditions in space. The publication date of these studies ranged from 1999 to 2020. A relatively similar proportion of these studies were conducted either on the International Space Station or in parabolic flight, with one performed in supine positioning to simulate weightlessness. The included studies discuss acute pathologies, such as abdominal emergencies, decompression sickness, deep venous thrombosis, acute lung pathologies, sinusitis, musculoskeletal trauma, genitourinary emergencies, and ocular emergencies. While ultrasound has shown promise in addressing various acute conditions, significant knowledge gaps remain, especially in gastrointestinal, cardiac, vascular, and reproductive emergencies. As we venture further into space, expanding our medical expertise becomes vital to ensure astronaut safety and mission success.


Follow the money: a closer look at US tobacco industry marketing expenditures.
While much of the concern with tobacco industry marketing has focused on direct media advertising, a less explored form of marketing strategy is to discount prices. Price discounting is important because it keeps the purchase price low and can undermine the impact of tax increases. We examine annual US marketing expenditures from 1975 to 2019 by the largest cigarette and smokeless tobacco companies as reported to the Federal Trade Commission. We consider three categories: direct advertising, promotional allowances and price discounting. In addition to considering trends in these expenditures, we examine how price discounting expenditures relate to changes in product prices and excise taxes. US direct advertising expenditures for cigarettes fell from 80% of total industry marketing expenditures in 1975 to less than 3% in 2019, while falling from 39% in 1985 to 6% in 2019 for smokeless tobacco. Price discounting expenditures for cigarettes became prominent after the Master Settlement Agreement and related tax increases in 2002. By 2019, 87% of cigarette marketing expenditures were for price discounts and 7% for promotional allowances. Smokeless marketing expenditures were similar: 72% for price promotions and 13% for promotional allowances. Price discounting increased with prices and taxes until reaching their currently high levels. Between 1975 and 2019, direct advertising dramatically fell while price discounting and promotional expenditures increased. Local, state and federal policies are needed that apply non-tax mechanisms to increase tobacco prices and restrict industry contracts to offset industry marketing strategies. Further study is needed to better understand industry decisions about marketing expenditures.


Composition Modulation of Ionic Liquid Hybrid Electrolyte for 5 V Lithium-Ion Batteries.
Electrolyte is a key component in high-voltage lithium-ion batteries (LIBs). Bis(trifluoromethanesulfonyl)imide-based ionic liquid (IL)/organic carbonate hybrid electrolytes have been a research focus owing to their excellent balance of safety and ionic conductivity. Nevertheless, corrosion of Al current collectors at high potentials usually happens for this kind of electrolyte. In this study, this long-standing problem is solved via the modulation of the IL/carbonate ratio and LiPF6 concentration in the hybrid electrolyte. The proposed electrolyte suppresses Al dissolution and electrolyte oxidation at 5 V (vs Li+/Li) and thus allows for ideal lithiation/delithiation performance of a high-voltage LiNi0.5Mn1.5O4 (LNMO) cathode even at 55 °C. The underlying mechanism is examined in this work. Excellent cycling stability (97% capacity retention) for an LNMO cathode after 300 cycles is achieved. This electrolyte shows good wettability toward a polyethylene separator and low flammability. In addition, satisfactory compatibility with both graphite and Si-based anodes is confirmed. The proposed electrolyte design strategies have great potential for applications in high-voltage LIBs.


Retinoic Acid Exerts Disease Stage-Dependent Effects on Pristane-Induced Lupus.
We previously showed that all-trans-retinoic acid (tRA), an active metabolite of vitamin A, exacerbated pre-existing autoimmunity in lupus; however, its effects before the development of autoimmunity are unknown. Here, using a pristane-induced model, we show that tRA exerts differential effects when given at the initiation vs. continuation phase of lupus. Unlike tRA treatment during active disease, pre-pristane treatment with tRA aggravated glomerulonephritis through increasing renal expression of pro-fibrotic protein laminin β1, activating bone marrow conventional dendritic cells (cDCs), and upregulating the interaction of ICAM-1 and LFA-1 in the spleen, indicating an active process of leukocyte activation and trafficking. Transcriptomic analysis revealed that prior to lupus induction, tRA significantly upregulated the expression of genes associated with cDC activation and migration. Post-pristane tRA treatment, on the other hand, did not significantly alter the severity of glomerulonephritis; rather, it exerted immunosuppressive functions of decreasing circulatory and renal deposition of autoantibodies as well as suppressing the renal expression of proinflammatory cytokines and chemokines. Together, these findings suggest that tRA differentially modulate lupus-associated kidney inflammation depending on the time of administration. Interestingly, both pre- and post-pristane treatments with tRA reversed pristane-induced leaky gut and modulated the gut microbiota in a similar fashion, suggesting a gut microbiota-independent mechanism by which tRA affects the initiation vs. continuation phase of lupus.


The management of stage I--II Hodgkin's disease with irradiation alone or combined modality therapy: the Stanford experience.
At Stanford University, between 1968 and 1978, 230 patients with pathologic stage I--II Hodgkin's disease were treated on prospective clinical trials with either irradiation alone or irradiation followed by 6 cycles of adjuvant combination chemotherapy. The actuarial survival at 10 yr was 84% for patients in either treatment group. Freedom from relapse at 10 yr was 77% among patients treated with irradiation alone and 84% after treatment with combined modality therapy [p(Gehan) = 0.09]. Freedom from second relapse at 10 yr was 89% and 94%, respectively [p(Gehan) = 0.56]. Several prognostic factors were evaluated in order to identify patients at high risk for relapse or with poor ultimate survival after initial treatment with irradiation alone. Systemic symptoms, histologic subtype, age, and limited extranodal involvement (E-lesions) did not affect the prognosis of patients and failed to identify patients whose survival could be improved by the routine use of combined modality therapy. Patients with large mediastinal masses (mediastinal mass ratio greater than or equal to 1/3) had a significantly poorer freedom from relapse when treated with irradiation alone than when treated initially with combined modality therapy [45% versus 81% at 10 yr, p(Gehan) = 0.03). The 10-yr survival of these patients, however, was not significantly different (84% versus 74%). The implications of these observations on the management of patient with early stage Hodgkin's disease are discussed.


ATP as a source of interstitial adenosine in the rat heart.
The contribution of neuronal ATP to interstitial adenosine levels was investigated in isolated perfused rat hearts. Ventricular surface transudates, representing interstitial fluid, were analyzed for norepinephrine, ATP, and adenosine. Exocytotic release of norepinephrine was induced by electrical stimulation of cardiac efferents emanating from the stellate ganglion. Ganglion stimulation increased contractility, interstitial norepinephrine, ATP, and adenosine. Interstitial adenosine was 11- to 27-fold higher than interstitial ATP, suggesting that the released ATP is unlikely the only source of adenosine. In the presence of AOPCP (alpha,beta-methyleneadenosine 5'-diphosphate), an ecto-5'-nucleotidase inhibitor, the ganglion-stimulated increase in interstitial ATP and adenosine reached levels similar to those in the absence of AOPCP, also suggesting that adenosine does not derive from extracellular ATP. The perfusate Ca2+ was raised from 1 to 4 mM to determine the importance of the enhanced contractile function on the levels of norepinephrine, ATP, and adenosine. The results were increases in contractility and interstitial norepinephrine, ATP, and adenosine, which were not suppressed with atenolol, indicating a norepinephrine-independent release of ATP and adenosine. Reserpine treatment and administration of guanethidine depleted the catecholamine stores and diminished the catecholamine release, respectively. However, neither agent altered Ca2+-induced increases in ATP and adenosine. It is concluded that the amount of neuronal-derived ATP is low and most likely does not contribute significantly to interstitial levels of adenosine. Furthermore, elevations in interstitial norepinephrine, ATP, and adenosine are associated with neuronal-independent increases in contractile function.


Differential regulation of amounts of the guanine-nucleotide-binding proteins Gi and Go in neuroblastoma x glioma hybrid cells in response to dibutyryl cyclic AMP.
Incubation of the neuroblastoma x glioma hybrid cell line NG108-15 in tissue culture with dibutyryl cyclic AMP (1 mM) for up to 8 days produced a morphological differentiation of the cells, during which they extended neurite-like processes. Pertussis-toxin-catalysed ADP-ribosylation indicated that amounts of guanine-nucleotide-binding proteins (G-proteins), which are substrates for this toxin, were approximately doubled in membranes from the 'differentiated' cells in comparison with the control cells. Immunoblotting of membranes derived from either untreated or dibutyryl cyclic AMP-treated cells with anti-peptide antisera specific for the alpha subunits of the pertussis-toxin-sensitive G-proteins Gi and Go demonstrated that amounts of these G-proteins were reciprocally modulated during the differentiation process. In comparison with the untreated cells, the amount of Gi in the 'differentiated' cells was decreased, whereas the amount of Go was substantially increased. Stimulation of high-affinity GTPase activity in response to opioid peptides, which in this cell line interact with an opioid receptor of the delta subclass, was much decreased, and inhibition of adenylate cyclase activity was almost entirely attenuated in the 'differentiated'-cell membranes in comparison with membranes of untreated cells. Opioid receptor number was also decreased in membranes of the dibutyryl cyclic AMP-treated cells in comparison with the control cells. These data demonstrate that relatively small changes in the observed pattern of pertussis-toxin-catalysed ADP-ribosylation of membranes can mask more dramatic alterations in amounts of the individual pertussis-toxin-sensitive G-proteins, and further demonstrate the importance of methodologies able to discriminate between the different gene products.


Rescue of a Cilevirus from infectious cDNA clones.
Reverse genetics systems represent an important tool for studying the molecular and functional processes of viral infection. Citrus leprosis virus C (CiLV-C) (genus Cilevirus, family Kitaviridae) is the main pathogen responsible for the citrus leprosis (CL) disease in Latin America, one of the most economically important diseases of the citrus industry. Molecular studies of this pathosystem are limited due to the lack of infectious clones. Here, we report the construction and validation of a CiLV-C infectious cDNA clone based on an agroinfection system. The two viral RNA segments (RNA1 and RNA2) were assembled into two binary vectors (pJL89 and pLXAS). Agroinfiltrated Nicotiana benthamiana plants showed a response similar to that observed in the natural infection process with the formation of localized lesions restricted to the inoculated leaves. The virus recovered from the plant tissue infected with the infectious clones can be mechanically transmitted between N. benthamiana plants. Detection of CiLV-C subgenomic RNAs (sgRNAs) from agroinfiltrated and mechanically inoculated leaves further confirmed the infectivity of the clones. Finally, partial particle-purification preparations or sections of CiLV-C-infected tissue followed by transmission electron microscopy (TEM) analysis showed the formation of CiLV-C virions rescued by the infectious clone. The CiLV-C reverse genetic system now provides a powerful molecular tool to unravel the peculiarities of the CL pathosystem.


[Dementia and extrapyramidal problems caused by long-term valproic acid].
Among the side-effects attributed to valproic acid (VPA), the occurrence of Parkinsonian syndromes and cognitive impairment is very uncommonly reported. We describe five cases of reversible associated Parkinsonism. These cases were observed in epileptic patients, 57 to 74 years old, two women and three men. Extrapyramidal disorders appeared after various durations of treatment (from 6 months to 10 years). Dementia characterized by an insidious onset was associated in three cases and bradypsychia in one case. Brain pseudoatrophy was present in three patients. In all cases the signs and symptoms improved some weeks or months after discontinuation of VPA. In the literature some cases, usually in young adults or children, have been reported. In a prospective study, Armon et al. found various abnormal symptoms and signs related to motor and cognitive function impairment in patients with long-term VPA therapy. These side-effects may be related to a disturbance in the gabaergic pathways in the basal ganglia system. It is of interest to consider that delta 2-valproic acid, a metabolite of VPA, is especially accumulated in selected areas of the brain: the substantia nigra, superior and inferior colliculus, hippocampus and medulla.


A SCID patient reconstituted with HLA-incompatible fetal stem cells as a model for studying transplantation tolerance.
We studied a severe combined immunodeficiency (SCID) patient who received transplantations with completely HLA-mismatched fetal liver and thymus from two different donors. The patient is now 14 years old, healthy and shows normal immunoresponses to recall antigens. His T cells are of donor origin, whereas the monocytes, B cells, and natural killer (NK) cells are of the recipient. The successful immunological reconstitution raised questions as to how T and B cells could collaborate across an HLA barrier and how tolerance was achieved. We have shown that tetanus toxin-specific T cell clones isolated from this patient recognized this antigen in the context of host and not of donor HLA-DR, indicating that those cells were educated in the host environment, presumably the thymus. Despite this, an unexpectedly high frequency of host-reactive clones was found that could recognize MHC antigens of the host. It was particularly striking that CD8+ CTL clones were obtained that recognized class I MHC antigens on the host cells. Nevertheless, the patient did not show any sign of acute or chronic graft-versus-host disease (GVHD). These data indicated that no or only incomplete clonal deletion had taken place in this patient and suggest the presence of a peripheral suppressor mechanism. Thus far, we have no indication for the existence of suppressor T cells. Inasmuch as it was found that host-reactive T cells fail to produce IL-4, which is exceptional for CD4+ T cells, we are exploring the possibility that abnormal cytokine production patterns of host-reactive T cells are associated with suppression of these cells in vivo.


A current analysis of primary lymphoma of the thyroid.
Over a 9-year period ending in May 1990, 27 patients with histologically proved thyroid lymphoma were assessed and treated. There were 24 female and three male patients with a median age of 67 years at the time of diagnosis (age range, 39 to 85 years). The usual presentation was that of a rapidly enlarging neck mass. Incisional biopsy was the diagnostic procedure of choice; however, nine of 27 patients underwent diagnostic partial or total thyroidectomy based on a preoperative impression of thyroid carcinoma. All 27 patients had non-Hodgkin's lymphomas of intermediate (77%) or high (23%) grade. Detailed staging was carried out in 25 patients; seven patients (28%) had disease confined to the thyroid gland (stage I), while 18 (73%) had accompanying disease in cervical lymph nodes or the mediastinum (stage II). Combined multiagent chemotherapy and irradiation was given to 19 of 25 staged patients (76%). Actuarial, overall 5-year survival for all patients was 70% with 48 months being the median follow-up for living patients (follow-up range, 3 to 102 months). Of a number of factors evaluated using log-rank survival tests, only the absence of dysphagia at the time of hospital admission, a primary tumor mass not greater than 10 cm, restriction of disease to the thyroid gland, and the absence of mediastinal lymph node involvement were statistically significant predictors of improved survival. Surgery should usually be restricted to diagnostic biopsy, as there is infrequently a role for resection in the management of thyroid lymphoma, given the effectiveness of combined multiagent chemotherapy and radiotherapy.


Heritability of the limbic networks.
Individual differences in cognitive ability and social behaviour are influenced by the variability in the structure and function of the limbic system. A strong heritability of the limbic cortex has been previously reported, but little is known about how genetic factors influence specific limbic networks. We used diffusion tensor imaging tractography to investigate heritability of different limbic tracts in 52 monozygotic and 34 dizygotic healthy adult twins. We explored the connections that contribute to the activity of three distinct functional limbic networks, namely the dorsal cingulum ('medial default-mode network'), the ventral cingulum and the fornix ('hippocampal-diencephalic-retrosplenial network') and the uncinate fasciculus ('temporo-amygdala-orbitofrontal network'). Genetic and environmental variances were mapped for multiple tract-specific measures that reflect different aspects of the underlying anatomy. We report the highest heritability for the uncinate fasciculus, a tract that underpins emotion processing, semantic cognition, and social behaviour. High to moderate genetic and shared environmental effects were found for pathways important for social behaviour and memory, for example, fornix, dorsal and ventral cingulum. These findings indicate that within the limbic system inheritance of specific traits may rely on the anatomy of distinct networks and is higher for fronto-temporal pathways dedicated to complex social behaviour and emotional processing.


A review on biomaterials for ovarian tissue engineering.
Considerable challenges in engineering the female reproductive tissue are the follicle's unique architecture, the need to recapitulate the extracellular matrix, and tissue vascularization. Over the years, various strategies have been developed for preserving fertility in women diagnosed with cancer, such as embryo, oocyte, or ovarian tissue cryopreservation. While autotransplantation of cryopreserved ovarian tissue is a viable choice to restore fertility in prepubertal girls and women who need to begin chemo- or radiotherapy soon after the cancer diagnosis, it is not suitable for all patients due to the risk of having malignant cells present in the ovarian fragments in some types of cancer. Advances in tissue engineering such as 3D printing and ovary-on-a-chip technologies have the potential to be a translational strategy for precisely recapitulating normal tissue in terms of physical structure, vascularization, and molecular and cellular spatial distribution. This review first introduces the ovarian tissue structure, describes suitable properties of biomaterials for ovarian tissue engineering, and highlights recent advances in tissue engineering for developing an artificial ovary. STATEMENT OF SIGNIFICANCE: The increase of survival rates in young cancer patients has been accompanied by a rise in infertility/sterility in cancer survivors caused by the gonadotoxic effect of some chemotherapy regimens or radiotherapy. Such side-effect has a negative impact on these patients' quality of life as one of their main concerns is generating biologically related children. To aid female cancer patients, several research groups have been resorting to tissue engineering strategies to develop an artificial ovary. In this review, we discuss the numerous biomaterials cited in the literature that have been tested to encapsulate and in vitro culture or transplant isolated preantral follicles from human and different animal models. We also summarize the recent advances in tissue engineering that can potentially be optimal strategies for developing an artificial ovary.


Neutron capture and stellar synthesis of heavy elements.
The neutron buildup processes of heavy-element synthesis in stars have left us a number of tantalizing nuclear clues to the early history of solarsystem material. Considerable illumination of our past history has been achieved through studying the correlations between abundance and neutroncapture cross section. Measurement of these cross sections required the development of new techniques for measuring time of flight of pulsed neutron beams. A clear conclusion is that many of our heavy elements were produced inside stars, which can be thought of as giant fast reactors. Extensions of these capture studies have given a clearer picture of additional. violent processes which produced some heavy elements, particularly thorium and uranium. In addition, the correlations have been used for obtaining an independent measure of the time that has elapsed since the solar-system material was synthesized. Finally, data on capture cross section relative to abundance will enable us to determine rather accurately the solar-system abundances of gaseous, volatile, and highly segregated elements.


Adiponectin may mediate the association between omentin, circulating lipids and insulin sensitivity: results from the KORA F4 study.
Reduced circulating omentin levels have been reported in obesity and type 2 diabetes, but data were mostly derived from univariate analyses in small study samples. This study aimed to investigate the relationship between omentin, abnormal glucose tolerance and related metabolic factors in a large population-based cross-sectional study. Serum omentin was measured by ELISA in 1092 participants of the German KORA F4 survey (2006-2008). Associations between omentin serum levels, glucose tolerance (assessed with an oral glucose tolerance test) and diabetes-related factors were estimated using logistic and linear regression models respectively. Serum levels of omentin were not related to categories of glucose tolerance. However, serum omentin was positively associated with whole-body insulin sensitivity index (ISI (composite)) and HDL cholesterol and showed inverse associations with 2-h post-load glucose, fasting insulin, homeostasis model assessment-estimated insulin resistance, BMI and triglycerides (all P≤0.03 after adjustment for age, sex and lifestyle factors). Further adjustment for BMI and/or serum lipids attenuated the associations with parameters of glucose metabolism, whereas adjustment for serum adiponectin virtually abolished all aforementioned associations. In contrast, adjustment for omentin had no effect on the positive association between adiponectin levels and ISI (composite). The data from this large population-based cohort show that circulating omentin levels are associated with insulin sensitivity. Our observations further suggest that omentin acts via upregulation of adiponectin, which in turn affects lipid metabolism and thereby also indirectly enhances insulin sensitivity, but mechanistic studies are required to corroborate this hypothesis.


Bay-region distortions in a methanol adduct of a bay-region diol epoxide of the carcinogen 5-methylchrysene.
The three-dimensional structure of the product of the reaction of a diol epoxide of the carcinogen 5-methylchrysene with methanol has been determined by an X-ray diffraction analysis. The diol epoxide used to obtain this compound contains a stereochemically hindered bay region because of the location of the 5-methyl group, and this might be expected to affect the type of chemical reaction that occurs. The crystal structure analysis of this adduct of a polycyclic aromatic hydrocarbon (PAH) showed that a methoxy group has been added at the carbon atom of the epoxy group that is nearest to the aromatic system. The bond that is formed is axial to the ring system so that the carbon and hydrogen atoms of the methoxy group are considerably displaced from the PAH ring plane. The bay-region methyl group at position 5 is displaced out of the ring plane in the opposite direction. The major steric distortion in this methanol adduct is shown, by a comparison with crystal structures of related non-methylated compounds, to be in the area of the 5-methyl group and not in the tetrol-bearing ring. The steric effects that caused the axial conformation of the newly formed bond would also be expected to pertain in the DNA adduct of a PAH with a bay-region methyl group. Since the presence of the bay-region methyl group in 5-methylchrysene has been shown to enhance the carcinogenicity of this PAH over the parent compound or compounds with methyl groups in other positions of the molecule, it might be anticipated that this axial bond is found in carcinogenic lesions in DNA, and that any factor that ensures this axial conformation may accentuate the carcinogenic potential of a PAH of the appropriate size.


Mutants of Polysphondylium pallidum showing delayed modifications of glycoproteins are altered in a regulatory signal for development.
Binding of a monoclonal antibody, mAb293, to cell-surface glycoproteins of Polysphondylium pallidum is known to be blocked by L-fucose, and Fab of this antibody has been shown to inhibit intercellular adhesion of aggregation-competent cells. Mutants with delayed expression of the carbohydrate epitope, ep293, recognized by the antibody, have been shown to be retarded and altered in cell aggregation. The present study shows that ep293 is a modification of carbohydrate structure that is subject to regulation not only in mutant but also in wild-type cells; ep293 is expressed at an early stage of exponential growth in wild-type and only after 12 h of starvation in mutant PN6002. Proteins are already glycosylated before the epitope is expressed. The developmental regulation of pallidin, a lectin known to be an unglycosylated protein, was investigated in parallel with ep293 using a monoclonal antibody. Pallidin was expressed at about the same time as the carbohydrate epitope in cells of the wild-type as well as the mutant. These results indicate a regulatory signal to which various events are coupled. Induction of ep293 and expression of pallidin are two of these events, and mutants such as PN6002 are altered in the timing of the signal.