Effects of a new parallel primary healthcare centre and on-campus training programme on history taking, physical examination skills and medical students' preparedness: a prospective comparative study in Taiwan.
The primary healthcarecentre (PHCC) is the first place that medical students experience patient contact. Usually, medical students are frustrated by a lack of proper skills training for on-campus history taking (HT), physical examination (PE) and self-directed learning (SDL) to prepare for their PHCC and inhospital patient contact. For pre-clerks, this study aims to compare the effectiveness of PHCC training and PHCC training in combination with on-campus HT and PE training modules (PHCC+on-campus) on their clerkship preparedness. This comparative study utilised prospective, consecutive, end of pre-clerkship group objective structured clinical examination (GOSCE), beginning of clerkship OSCE and self-administered Preparation for Hospital Practice Questionnaire (PHPQ). 128 pre-clinical clerk volunteers (64 each year) receiving PHCC training (7 week PHCCtraining in addition to 7 week assignment based group learning, academic year 2014, controls) and PHCC training in combination with on-campus module training (academic year 2015, 7 week PHCCtraining in addition to 7 week on-campus sessions) were sequentially assessed before the module (week 1), at the end of the module (week 14) and at the beginning of clerkship (week 25). For overall HT and PE skills, both PHCC and PHCC+on-campus module trained pre-clerks performed better on OSCE than GOSCE. Additionally, the improvement was accompanied by higher self-reported PHPQ scores in 'confidence/coping' and 'SDL' domains. At the end of the pre-clerkship and the beginning of the clerkship stages, the degree of improvement in preparedness in 'confidence/coping' and 'SDL' domains was higher for those in the PHCC+on-campus group than for those in the PHCC group. Among the PHCC+on-campus module participants, a positive association was observed between high mean PHPQ-SDL scores and high OSCE scores. Our study suggests that the PHCC+on-campus module, which is paired faculty led and pre-trained dyad student assisted, is effective in developing a preclinical clerk's HT and PE skills and intensifying SDL/patient management abilities to prepare for hospital practice in clerkship.


Editor's Highlight: Candidate Risk Factors and Mechanisms for Tolvaptan-Induced Liver Injury Are Identified Using a Collaborative Cross Approach.
Clinical trials of tolvaptan showed it to be a promising candidate for the treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) but also revealed potential for idiosyncratic drug-induced liver injury (DILI) in this patient population. To identify risk factors and mechanisms underlying tolvaptan DILI, 8 mice in each of 45 strains of the genetically diverse Collaborative Cross (CC) mouse population were treated with a single oral dose of either tolvaptan or vehicle. Significant elevations in plasma alanine aminotransferase (ALT) were observed in tolvaptan-treated animals in 3 of the 45 strains. Genetic mapping coupled with transcriptomic analysis in the liver was used to identify several candidate susceptibility genes including epoxide hydrolase 2, interferon regulatory factor 3, and mitochondrial fission factor. Gene pathway analysis revealed that oxidative stress and immune response pathways were activated in response to tolvaptan treatment across all strains, but genes involved in regulation of bile acid homeostasis were most associated with tolvaptan-induced elevations in ALT. Secretory leukocyte peptidase inhibitor (Slpi) mRNA was also induced in the susceptible strains and was associated with increased plasma levels of Slpi protein, suggesting a potential serum marker for DILI susceptibility. In summary, tolvaptan induced signs of oxidative stress, mitochondrial dysfunction, and innate immune response in all strains, but variation in bile acid homeostasis was most associated with susceptibility to the liver response. This CC study has indicated potential mechanisms underlying tolvaptan DILI and biomarkers of susceptibility that may be useful in managing the risk of DILI in ADPKD patients.


Microperoxisomes in retinal pigment epithelium.
Microperoxisomes were found to be abundant in the retinal pigment epithelium of the human, rhesus monkey, mice, rats, domestic fowl, and frog by ultrastructural histochemistry. They were rare in other cells of the retina and choroid. These organelles had a granular matrix, ranged in diameter from 0.15 mum to 0.30 mum, and were bound by a single tripartite membrane which often maintained slender connections with the smooth endoplasmic reticulum and other microperoxisomes. They exhibited a positive reaction (electron opaque product) following incubation in diaminobenzidine and H2O2 for the demonstration of the peroxidatic activity of catalase (Novikoff et al., J. Histochem. Cytochem. 20: 1006, 1972). The reaction was inhibited by: (1) aminotriazole; (2) dichlorophenol-indophenol; (3) preheating at 95 degrees C.; or (4) elimination of H2O2. Microperoxisomes, like the well-known peroxisomes (microbodies) of liver cells have been inplicated in various aspects of lipid metabolism and the detoxification of H2O2. We demonstrated for the first time that microperoxisomes respond to drug-induced changes in lipid metabolism, as previously shown for peroxisomes. Nafenopin is a recently utilized drug which greatly decreases serum lipids, increases hepatic catalase activity, and induces an increased size and number of hepatic peroxisomes. Black, beige, albino, and obese mutant mice of the C57BL/6J strain treated with nafenopin for several weeks showed a two- to threefold increase in the number of microperoxisomes in the retinal pigment epithelium. Microperoxisomes of the retinal pigment epithelium may be involved in the transport, storage, and rapid turnover of lipids associated with the maintenance of photoreceptor outer segment disc membranes.


The promises of immunotherapy in gliomas.
Also owing to the limited efficacy of targeted therapies, there has been a renewed interest in targeting gliomas with immunotherapy. But despite considerable efforts using sophisticated approaches, proof of efficacy beyond case studies is still lacking. The purpose of this review is to summarize and discuss current immunotherapeutic approaches and efforts to understand mechanisms of response and resistance. The recent failure of large randomized clinical trials using targeted vaccines and checkpoint inhibitors to improve clinical outcome have underlined the grand challenges in this therapeutic arena and illustrated the necessity to understand the biology of immunotherapeutic interventions before conducting large randomized studies. However, these failures should not distract us from continuing to optimize immunotherapeutic concepts. The recent developments in transgenic T cell technologies and personalized vaccines but also rational combinatorial approaches offer tremendous opportunities and should be exploited carefully in early scientifically driven clinical trials. A profound understanding of the cellular and molecular mechanisms of response and resistance to immunotherapy to be gained from these thoroughly designed clinical trials will be essential to carve out successful strategies in selected patient populations.


Radiological evaluation of the Cresco system in combination with Osseospeed implants: a preliminary 3-year report.
In this preliminary study, the 3-year radiological outcomes of Osseospeed implant-supported fixed complete or partial prostheses made with two different laboratory protocols were compared. A convenience sample of 34 patients, who were either partially or completely edentulous in either jaw, were randomly assigned to two groups, of 17 patients each, using either a traditional laboratory protocol (control group) or the Cresco one (test group). The study's objective was an assessment of marginal bone loss around implants, measured on intraoral radiographs at 3-year follow-up. None of the implants inserted was lost during the study and radiological measurements of marginal bone level changes revealed that the mean marginal bone loss was respectively 0,73±0,33mm for test group and 0,88±1,13mm for control group. The differences between test and control groups were not statistically significant. This preliminary study did not demonstrate statistically significant differences in marginal bone loss around implant-prostheses prepared with the two different laboratory protocols, over the 3-year observational period.


Reinforcement history shapes primary visual cortical responses: An SSVEP study.
Efficient learning requires allocating limited attentional resources to meaningful stimuli and away from irrelevant stimuli. This prioritization may occur via covert attention, evident in the activity of the visual cortex. We used steady-state visual evoked potentials (SSVEPs) to assess whether associability-driven changes in stimulus processing were evident in visuocortical responses. Participants were trained on a learned-predictiveness protocol, whereby one stimulus on each trial accurately predicted the correct response for that trial, and the other was irrelevant. In a second phase the task was arranged so that all cues were objectively predictive. Participants' overt attention (eye gaze) was affected by each cue's reinforcement history, as was their covert attention (SSVEP responses). These biases persisted into Phase 2 when all stimuli were objectively predictive, thereby demonstrating that learned attentional processes are evident in basic sensory processing, and exert an effect on covert attention above and beyond the effects of overt gaze bias.


Integrated feature analysis and fuzzy rule-based system identification in a neuro-fuzzy paradigm.
Most methods of fuzzy rule-based system identification (SI) either ignore feature analysis or do it in a separate phase. This paper proposes a novel neuro-fuzzy system that can simultaneously do feature analysis and SI in an integrated manner. It is a five-layered feed-forward network for realizing a fuzzy rule-based system. The second layer of the net is the most important one, which along with fuzzification of the input also learns a modulator function for each input feature. This enables online selection of important features by the network. The system is so designed that learning maintains the nonnegative characteristic of certainty factors of rules. The proposed network is tested on both synthetic and real data sets and the performance is found to be quite satisfactory. To get an "optimal" network architecture and to eliminate conflicting rules, nodes and links are pruned and then the structure is retrained. The pruned network retains almost the same level of performance as that of the original one.


Genetic polymorphism and zoonotic potential of Enterocytozoon bieneusi from nonhuman primates in China.
Enterocytozoon bieneusi is an important zoonotic pathogen. To assess the human-infective potential of E. bieneusi in nonhuman primates (NHPs), we examined the prevalence and genotype distribution of E. bieneusi in 23 NHP species by PCR and sequence analysis of the ribosomal internal transcribed spacer (ITS). A total of 1,386 fecal specimens from NHPs from five provinces in China were examined, and E. bieneusi was detected in 158 (11.4%) specimens from five NHP species, including cynomolgus monkey (67.7%), rhesus macaque (8.8%), Japanese macaque (33.3%), white-headed langur (13.6%), and golden snub-nosed monkey (3.5%) (P < 0.0001). The infection rates were 70.2%, 21.5%, 8.5%, 7.5%, and 5.6% in Guangdong, Yunnan, Guangxi, Henan, and Sichuan Provinces, respectively (P < 0.0001). The prevalence was significantly higher in captive (13.7%) than in free-range (5.0%) animals (P < 0.0001). Altogether, 16 ITS genotypes were observed, including nine known genotypes (IV, D, Henan V, Peru8, PigEBITS7, EbpC, Peru11, BEB6, and I) and seven new genotypes (CM1 to CM7). The common genotypes included CM1, IV, and D, which were detected in 43, 31, and 30 specimens, respectively. Phylogenetic analysis revealed that seven known genotypes (but not BEB6 and I) and four new genotypes (CM1, CM2, CM3, and CM6) belonged to the previously described group 1 with zoonotic potential. Genotypes CM5 and CM7 clustered with group 2, whereas genotype CM4 did not belong to any of the previously proposed groups. It was concluded that humans and NHPs residing in the same geographical location shared the same E. bieneusi genotypes, indicating a potential role of these animals in the zoonotic transmission of E. bieneusi.


What Happened to Paul? Manifestation of Abnormal Pain Response for Individuals With Autism Spectrum Disorder.
During the progression of a pilot nutrition intervention designed to teach cooking skills to young adults with autism spectrum disorder (ASD), one participant-Paul-fell in the parking lot. Prior to the accident, Paul had been making significant gains in the program and had communicated in a number of ways his enthusiasm. After his accident, which resulted in broken and dislocated bones in his ankle, his demeanor was dramatically altered, program gains were lost, and staff noted the appearance of many new challenging behaviors. This article analyzes Paul's behavior in reference to the pain response in autism. For some time, it was believed that many individuals with ASD did not experience pain based on anecdotal reports of how individuals responded to injury with seeming indifference. This view has given way of late to a more nuanced understanding of how atypical sensory processing and stimulus over-selectivity spill over into pain pathways and pain amplification mechanisms. The consequence is not a reduction in pain sensation, but a different expression of pain, determined by that individual's particular communicative, cognitive, or physiological challenges. From this perspective, many of the disruptive and harmful behaviors that emerged after Paul's accident can be seen as a delayed response to the incident. This article concludes by arguing that professionals across all domains of health care need to begin to see behavior as communicative for those with ASD. This is particularly true of changes in behavior, which can be significant indicators of health care problems rather than something to be dismissed as another manifestation of the condition.


The efficacy of treatment for children with developmental speech and language delay/disorder: a meta-analysis.
A meta-analysis was carried out of interventions for children with primary developmental speech and language delays/disorders. The data were categorized depending on the control group used in the study (no treatment, general stimulation, or routine speech and language therapy) and were considered in terms of the effects of intervention on expressive and receptive phonology, syntax, and vocabulary. The outcomes used in the analysis were dependent on the aims of the study; only the primary effects of intervention are considered in this review. These were investigated at the level of the target of therapy, measures of overall linguistic development, and broader measures of linguistic functioning taken from parent report or language samples. Thirty-six articles reporting 33 different trials were found. Of these articles, 25 provided sufficient information for use in the meta-analyses; however, only 13 of these, spanning 25 years, were considered to be sufficiently similar to be combined. The results indicated that speech and language therapy might be effective for children with phonological or expressive vocabulary difficulties. There was mixed evidence concerning the effectiveness of intervention for children with expressive syntax difficulties and little evidence available considering the effectiveness of intervention for children with receptive language difficulties. No significant differences were found between interventions administered by trained parents and those administered by clinicians. The review identified longer duration (>8 weeks) of therapy as being a potential factor in good clinical outcomes. A number of gaps in the evidence base are identified.


Evaluation of the role for prolactin-releasing peptide in prolactin secretion induced by ether stress and suckling in the rat: comparison with vasoactive intestinal peptide.
Prolactin (PRL)-releasing peptide (PrRP) is a recently discovered hypothalamic peptide possessing a specific stimulatory action on PRL secretion. In this study, we examined whether PrRP plays a role in mediating ether stress- and suckling-induced PRL secretion in rats through administering anti-PrRP antisera intracerebroventricularly. For comparison, we also tested the effect of anti-vasoactive intestinal peptide (VIP) antisera on the hormonal responses, since VIP is another candidate for a physiological PRL-releasing factor. The immunoneutralization of VIP, but not of PrRP, led to a significant suppression of PRL responses to both ether and suckling. These results suggest that PrRP may not play a significant role, or at least play a much weaker role than VIP, in mediating PRL release induced by ether stress and suckling in the rat.


Gender differences in experimental aortic aneurysm formation.
It is hypothesized that a male predominance, similar to that in humans, persists in a rodent model of experimental abdominal aortic aneurysm (AAA) via alterations in matrix metalloproteinases (MMPs). Group I experiments were as follows: elastase perfusion of the infrarenal aorta was performed in male (M) and female (F) rats. At 14 days, aortas were harvested for immunohistochemistry, real-time polymerase chain reaction (PCR), and zymography. Group II experiments were the following: abdominal aorta was transplanted from F or M donors into F or M recipients. At 14 days, rodents that had undergone transplantation underwent elastase perfusion. In group III, male rats were given estradiol or sham 5 days before elastase perfusion. In group I, M rats had larger AAAs with higher frequency than did F rats. M rat aortas had more significant macrophage infiltrates and increased matrix metalloproteinase (MMP)-9 production and activity. In group II, M-to-M aortic transplants uniformly developed aneurysms after elastase perfusion, whereas F-to-F aortic transplants remained resistant to aneurysm formation. F aortas transplanted into M recipients, however, lost aneurysm resistance. In group III, estradiol-treated rats demonstrated smaller aneurysms and less macrophage infiltrate and MMP-9 compared with M controls after elastase. These data provide evidence of gender-related differences in AAA development, which may reflect an estrogen-mediated reduction in macrophage MMP-9 production.


Enrichment of ligands with molecular dockings and subsequent characterization for human alcohol dehydrogenase 3.
Alcohol dehydrogenase 3 (ADH3) has been assigned a role in nitric oxide homeostasis due to its function as an S-nitrosoglutathione reductase. As altered S-nitrosoglutathione levels are often associated with disease, compounds that modulate ADH3 activity might be of therapeutic interest. We performed a virtual screening with molecular dockings of more than 40,000 compounds into the active site of human ADH3. A novel knowledge-based scoring method was used to rank compounds, and several compounds that were not known to interact with ADH3 were tested in vitro. Two of these showed substrate activity (9-decen-1-ol and dodecyltetraglycol), where calculated binding scoring energies correlated well with the logarithm of the k (cat)/K (m) values for the substrates. Two compounds showed inhibition capacity (deoxycholic acid and doxorubicin), and with these data three different lines for specific inhibitors for ADH3 are suggested: fatty acids, glutathione analogs, and cholic acids.


International registries of families at high risk of pancreatic cancer.
To describe the need for multinational registries of families at high risk of pancreatic cancer and the issues surrounding identification of such families. A consensus position was published describing surveillance of individuals at high risk of pancreatic cancer. Hereditary pancreatitis patients, people with Peutz-Jeghers syndrome, individuals with CDKN2A or BRCA1/2 mutations with a family history of pancreatic cancer and kindred with multiple pancreatic cancers were considered suitable for research-based screening. Mutations responsible for familial predisposition are mostly unknown, although BRCA2 mutations have been identified in some families and a mutation in the palladin gene has been shown to segregate with pancreatic cancer in one kindred. Specific autosomal dominant inheritance of pancreatic cancer risk seems to involve anticipation; this finding aids identification of families and determination of individual risk. Diabetes mellitus is an early symptom of pancreatic cancer, but recent publications suggest that it may not be a significant predisposing factor; this remains controversial. However, in the context of hereditary pancreatitis, diabetes probably does predispose to pancreatic cancer as shown in a recent description of French families. Appropriate inclusion of patients within registries of high-risk families provides a framework for secondary screening and research on risk stratification and early tumorigenesis. and IAP.


Intraoperative colonic irrigation in the management of left sided large bowel emergencies in Jos University Teaching Hospital, Nigeria.
To evaluate the safety and benefits of antegrade intraoperative colonic irrigation (lavage) and primary anastomosis, after colonic resection, in the treatment of left sided large bowel emergencies. A prospective descriptive study. Jos University Teaching Hospital, Jos, Nigeria. Thirty seven patients with an average age of 44.86 +/- 16.15 years. Sigmoid colectomy was performed in twenty two sigmoid volvulus, five sigmoid cancer, two faecal fistulae and one sigmoid injury. Left hemicolectomy was offered in four descending colon cancer, one descending colon injury, while anterior resection was carried out in two rectal cancers. Primary anastomosis was performed after intraoperative colonic lavage. The operative mortality was 2.7%, anastomotic leakage rate 2.7% and superficial wound infection occurred in 10.81%. The average duration of hospital stay was 22.76 +/- 11.26 days. Intraoperative colonic lavage added 35.79 +/- 7.25 minutes to the operating time. The results of this study suggest that intraoperative colonic lavage is an effective method enabling the surgeon to perform a primary anastomosis with reasonable safety after emergency resection of selected distal colonic lesions.


Endothelial nitric oxide synthase protects aortic allografts from the development of transplant arteriosclerosis.
Inducible nitric oxide synthase (iNOS) is up-regulated in rejecting allografts and is protective against allograft arteriosclerosis; it suppresses neointimal smooth muscle cell accumulation and inhibits adhesion of platelets and leukocytes to the endothelium. However, the functional importance of endothelial NOS (eNOS) in the rejecting allografts remains unclear. We examined the effects of selective eNOS deficiency in aortic allografts in a murine chronic rejection model using grafts from eNOS knockout (KO) mice (C57BL/6 background; H2b) and normal C3H (H2K) as recipients. Grafts from wild-type C57BL/6 mice served as controls. Grafts from iNOS KO mice served as a second group of controls where the contribution from iNOS was eliminated but eNOS was preserved. Aortic grafts were harvested and analyzed at days 10-14, 18-22, and 26-30 after transplantation. Endothelial NOS-deficient grafts showed significantly increased intima/media ratios at days 26-30 compared to controls. Immunostaining demonstrated that in eNOS KO grafts, eNOS was not detectable whereas iNOS was expressed prominently in infiltrating recipient mononuclear cells. In control grafts, eNOS expression was preserved in the endothelium even by day 30, and associated with a decrease in intimal thickening. We further demonstrated that early overexpression of iNOS by ex vivo gene transfer completely prevented the development of arteriosclerosis associated with eNOS deficiency. We found that eNOS plays a protective role in allografts, and that in eNOS-deficient allografts, early overexpression of iNOS is capable of preventing the development of allograft arteriosclerosis. In allografts with dysfunctional vascular endothelium and impaired eNOS activity as a result of ischemia or native arteriosclerotic disease, iNOS gene therapy may serve to improve their long-term survival and function.


Migfilin's elimination from osteoarthritic chondrocytes further promotes the osteoarthritic phenotype via β-catenin upregulation.
Osteoarthritis (OA) is a debilitating disease of the joints characterized by cartilage degradation but to date there is no available pharmacological treatment to inhibit disease progression neither is there any available biomarker to predict its development. In the present study, we examined the expression level and possible involvement of novel cell-ECM adhesion-related molecules such as Iintegrin Linked Kinase (ILK), PINCH, parvin, Mig-2 and Migfilin in OA pathogenesis using primary human articular chondrocytes from healthy individuals and OA patients. Our findings show that only ILK and Migfilin were upregulated in OA compared to the normal chondrocytes. Interestingly, Migfilin silencing in OA chondrocytes rather exacerbated than ameliorated the osteoarthritic phenotype, as it resulted in even higher levels of catabolic and hypertrophic markers while at the same time induced reduction in ECM molecules such as aggrecan. Furthermore, we also provide a link between Migfilin and β-catenin activation in OA chondrocytes, showing Migfilin to be inversely correlated with β-catenin. Thus, the present study emphasizes for the first time to our knowledge the role of Migfilin in OA and highlights the importance of cell-ECM adhesion proteins in OA pathogenesis.


Comparing actual and perceived causes of fever among community members in a low malaria transmission setting in northern Tanzania.
To compare actual and perceived causes of fever in northern Tanzania. In a standardised survey, heads of households in 30 wards in Moshi, Tanzania, were asked to identify the most common cause of fever for children and for adults. Responses were compared to data from a local hospital-based fever aetiology study that used standard diagnostic techniques. Of 810 interviewees, the median (range) age was 48 (16, 102) years and 509 (62.8%) were women. Malaria was the most frequently identified cause of fever, cited by 353 (43.6%) and 459 (56.7%) as the most common cause of fever for children and adults, respectively. In contrast, malaria accounted for 8 (2.0%) of adult and 6 (1.3%) of paediatric febrile admissions in the fever aetiology study. Weather was the second most frequently cited cause of fever. Participants who identified a non-biomedical explanation such as weather as the most common cause of fever were more likely to prefer a traditional healer for treatment of febrile adults (OR 2.7, P < 0.001). Bacterial zoonoses were the most common cause of fever among inpatients, but no interviewees identified infections from animal contact as the most common cause of fever for adults; two (0.2%) identified these infections as the most common cause of fever for children. Malaria is perceived to be a much more common cause of fever than hospital studies indicate, whereas other important diseases are under-appreciated in northern Tanzania. Belief in non-biomedical explanations of fever is common locally and has important public health consequences.


[Effect of "vilon" on cirrhotically changed rat liver. Liver regeneration, and status of glycogen-forming function of hepatocytes].
Effects of a dipeptide preparation "Vilon" on rehabilitation of functional activity of hepatocytes and regeneration of the cirrhotically altered rat liver were studied. The liver cirrhosis was produced by poisoning of rats for 4 months with carbon tetrachloride (CCl4). On the end of the poisoning with CCl4, one group of animals was not submitted to any further actions, whereas animals of the other group were injected "Vilon" (1.7 micrograms/kg) daily for 5 days. On smears of isolated hepatocytes, contents of total glycogen (TG), and its labile and stable fractions (LF and SF) were determined in addition to cell ploidy levels and the total protein content. In liver homogenates, activities of glucose-6-phosphatase (G6P), glycogen synthase (GS), and glycogen phosphorylase (GP) were measured. In 2 weeks after the drug application, G6P activity being reduced in cirrhosis 1.2 times, elevated under effect of "Vilon". In non-treated rats the contents of TG and its fractions and of G6P activity remained at the level characteristic of the cirrhotic liver prior to "Vilon" administration. In both groups of rats, GP and GS activities in the cirrhotically altered liver did not differ from their control values throughout the entire experiment. "Vilon" has been shown to exert a weak stimulating effect on regeneration of the cirrotically altered rat liver: in hepatocytes of the second group of rats the total protein content and ploidy levels were higher than those in the first group by 4.7 and 11.5%, respectively.


Medium for selective isolation of Cryptococcus neoformans.
A medium has been developed that permits the selective recovery of Cryptococcus neoformans from heavily contaminated materials. It employs creatinine as a nitrogen source, diphenyl (C(6)H(5)C(6)H(5)) and chloramphenicol as mold and bacterial inhibitors, and Guizotia abyssinica seed extract as a specific color marker. The medium has proved to be effective in the direct isolation of Cryptococcus neoformans from pigeon nests and from the air.


[Impact of androgen deprivation on the lipid profile and atherogenic risk in prostate cancer patients].
This study has aimed to analyze the changes observed in the lipid profile and atherogenic risk in prostate cancer patients subjected to androgen deprivation. Between 2001 and 2008, serum lipoproteins (total cholesterol, HDL, LDL and triglycerides) were determined in 636 patients. Of these, 129 were treated with maximum androgen blockade and 177 patients were only treated with LHRH analogue. The control group was formed by 339 subjected to prostate biopsy (212 with prostate cancer and 127 without prostate cancer). The atherogenic risk was calculated using the Castelli formula (total cholesterol/HDL). Mean atherogenic risk was 4.2 in the control group and 4 in the group of patients subjected to androgenic deprivation, p>0.05. The mean atherogenic risk in those subjected to monotherapy with LHRH analogues was 4.1 while it was 3.9 in patients subjected to maximal androgen blockade, p=0.02. We did not found significant differences for atherogenic risk according to length of treatment, p>0.05. The multivariate analysis confirmed that the treatment modality was the only significant variable influencing atherogenic risk. This study demonstrates that continuous androgen deprivation does not increase atherogenic risk in patients with prostate cancer. This risk also did not increase during the treatment. The association of bicalutamide to the LHRH analogue seems to have a protective effect on atherogenic risk.


Effects of loaded voluntary wheel exercise on performance and muscle hypertrophy in young and old male C57Bl/6J mice.
This study compared the capacity of young and old male C57Bl/6J mice to exercise with increasing resistance over 10 weeks, and its impact on muscle mass. Young mice (aged 15-25 weeks) were subjected to low (LR) and high (HR) resistance exercise, whereas only LR was used for old mice (107-117 weeks). Weekly patterns of voluntary wheel activity, food consumption and body weights were measured. Running patterns changed over time and with age, with two peaks of activity detected for young, but only one for old mice: speed and distance run was also less for old mice. The mass for six limb muscles was measured at the end of the experiment. The most pronounced increase in mass in response to exercise was for the soleus in young and old mice, and also quadriceps and gastrocnemius in young mice. Soleus and quadriceps muscles were analyzed histologically for myofiber number and size. A striking feature was the many small myofibers in response to exercise in young (but not old) soleus, whereas these were not present after exercise in young or old quadriceps. Overall, there was a striking difference in response to exercise between muscles and this was influenced by age.


Prospective associations between appetitive traits and weight gain in infancy.
Differences in appetitive traits such as food-cue or satiety responsiveness have been hypothesized to contribute to variability in weight gain. However, existing data were largely cross-sectional and could not exclude the possibility that differences in appetitive traits were consequences of differences in weight. We tested whether prospective associations between appetitive traits and subsequent weight were stronger than associations between weight and subsequent appetitive traits. Data were from Gemini, which is a population-based cohort of 2402 families with twins. Parents completed a Baby Eating Behavior Questionnaire to assess 4 appetitive traits for each twin at ages 3 and 15 mo. We obtained infant weights at 3, 9, and 15 mo from records of health professionals. Weight SD scores were calculated by using UK 1990 reference data. A path analysis was used to examine prospective associations in each direction over sequential 6-mo intervals and over the same 12-mo period, with the significance of differences between the 2 paths established with bootstrapping. Path analyses included 2213 infants. For each appetitive trait, the path to subsequent weight (standardized coefficients: 0.17-0.33) was significantly larger than the path from weight to subsequent appetite (coefficients: 0.07-0.13). Results were confirmed when both associations were analyzed by using changes from 3 to 15 mo. Longitudinal analyses showed that associations between appetitive traits and subsequent weight were stronger than between weight and subsequent appetite, which supports the idea that differences in appetitive traits, in conjunction with environmental opportunities to overeat, influence weight gain in early childhood.


Ethnically diverse urban transmission networks of Neisseria gonorrhoeae without evidence of HIV serosorting.
We aimed to characterise gonorrhoea transmission patterns in a diverse urban population by linking genomic, epidemiological and antimicrobial susceptibility data. Neisseria gonorrhoeae isolates from patients attending sexual health clinics at Barts Health NHS Trust, London, UK, during an 11-month period underwent whole-genome sequencing and antimicrobial susceptibility testing. We combined laboratory and patient data to investigate the transmission network structure. One hundred and fifty-eight isolates from 158 patients were available with associated descriptive data. One hundred and twenty-nine (82%) patients identified as male and 25 (16%) as female; four (3%) records lacked gender information. Self-described ethnicities were: 51 (32%) English/Welsh/Scottish; 33 (21%) white, other; 23 (15%) black British/black African/black, other; 12 (8%) Caribbean; 9 (6%) South Asian; 6 (4%) mixed ethnicity; and 10 (6%) other; data were missing for 14 (9%). Self-reported sexual orientations were 82 (52%) men who have sex with men (MSM); 49 (31%) heterosexual; 2 (1%) bisexual; data were missing for 25 individuals. Twenty-two (14%) patients were HIV positive. Whole-genome sequence data were generated for 151 isolates, which linked 75 (50%) patients to at least one other case. Using sequencing data, we found no evidence of transmission networks related to specific ethnic groups (p=0.64) or of HIV serosorting (p=0.35). Of 82 MSM/bisexual patients with sequencing data, 45 (55%) belonged to clusters of ≥2 cases, compared with 16/44 (36%) heterosexuals with sequencing data (p=0.06). We demonstrate links between 50% of patients in transmission networks using a relatively small sample in a large cosmopolitan city. We found no evidence of HIV serosorting. Our results do not support assortative selectivity as an explanation for differences in gonorrhoea incidence between ethnic groups.


Disproportion and dysmorphism in an adult Belgian population with Turner syndrome: risk factors for chronic diseases?
Turner syndrome (TS) is characterized by dysmorphism and body disproportion. TS women are also susceptible to a range of chronic disorders including arterial hypertension (AHT), osteoporosis, sensorineural hearing loss (SNHL), type 2 diabetes mellitus (DM2) and thyroid disease. The association between dysmorphism/body disproportion and chronic disease has never been studied in TS women. The effect of growth hormone treatment on body disproportion is also unclear. Objectives: to analyze dysmorphic features and body disproportion in TS women in relation to the presence of chronic disease and to document the effect of growth hormone therapy on body disproportion. 76 adult TS women with a regular follow up at the TS clinic UZ Ghent were invited to participate. Detailed body measurements were performed in 44 volunteering TS women. Scoring systems for overall dysmorphism, craniofacial dysmorphism, thoracic and limb abnormalities and skeletal disproportion were developed. TS women with a higher dysmorphism score were more at risk for AHT (p = 0.04) as well as those with a higher sitting height/standing height ratio (p < 0.05). Prevalence of AHT, osteoporosis and DM 2 was lower in TS women treated with GH during childhood (p < 0.05). Adult TS women with relatively short legs or with more physical dysmorphic stigmata were more at risk for AHT. GH therapy does not seem to increase the risk of chronic disease on the long term.


Impact of gender, ethnicity, meal component, and time interval between eating and reporting on accuracy of fourth-graders' self-reports of school lunch.
To validate fourth-graders' self-reports of school lunch by comparing their reports to lunch observations, and to determine the impact on accuracy of gender, ethnicity, meal component, and time interval between eating and reporting. Students were randomly selected, observed eating lunch, and interviewed the same day, next day, or Monday regarding Friday's lunch. Accuracy of reporting items was determined by tallying matched foods (items reported and observed), phantom foods (items reported but not observed), and omitted foods (items not reported but observed). Accuracy of reporting amount eaten was determined by calculating absolute and arithmetic differences. Subjects were 260 students: 89 same-day, 148 next-day, and 23 Monday recalls; 59 whites (30 boys) and 201 blacks (103 boys) from four schools. Rates for matched, phantom, and omitted foods; analysis of variance; Friedman's nonparametric analog of analysis of variance; Student-Newman-Keuls' post hoc comparisons. In regard to reporting items, the respective rates for matched, phantom, and omitted foods were 84%, 5%, and 16% for same-day recalls; 68%, 13%, and 32% for next-day recalls; and 38%, 48%, and 62% for Monday recalls. Rates for omitted and phantom foods were higher for Monday recalls than for next-day recalls, which were higher than for same-day recalls (P < .05 for all). In regard to reporting amounts, analysis by gender, ethnicity, and time interval failed to yield significant main or interaction effects. When children correctly reported items eaten, they were quite accurate in reporting amounts eaten. Omitted food rates were lowest for beverage, followed by entree, and highest for miscellaneous and condiment. Even under the best conditions (ie, reporting within 90 minutes after eating school lunch), children have difficulty accurately reporting what they have eaten. As the time interval between eating and reporting increases, accuracy decreases markedly. Techniques that improve reporting of items eaten should result in improved accuracy of reporting amounts eaten.


Pump light distribution in a laser rod pumped exfocally in a rotational ellipsoid.
In a rotational ellipsoidal exfocal pumping system the linear lamp is arranged between vertex and nearest focus, and the laser rod is aligned between the second focus and the other vertex along the major axis of a rotational ellipsoidal mirror. For this optical pumping system, a calculation of the pump light distribution in the laser rod was performed on a computer by use of a ray tracing procedure. The calculations take account of reflection losses, multiple reflections, and shadowing at the end faces of the laser rod and the lamp. A series of diagrams presents the results of the computer calculations, which are also compared with experimental results.


Relative roles of the cellular and humoral responses in the Drosophila host defense against three gram-positive bacterial infections.
Two NF-kappaB signaling pathways, Toll and immune deficiency (imd), are required for survival to bacterial infections in Drosophila. In response to septic injury, these pathways mediate rapid transcriptional activation of distinct sets of effector molecules, including antimicrobial peptides, which are important components of a humoral defense response. However, it is less clear to what extent macrophage-like hemocytes contribute to host defense. In order to dissect the relative importance of humoral and cellular defenses after septic injury with three different gram-positive bacteria (Micrococcus luteus, Enterococcus faecalis, Staphylococcus aureus), we used latex bead pre-injection to ablate macrophage function in flies wildtype or mutant for various Toll and imd pathway components. We found that in all three infection models a compromised phagocytic system impaired fly survival--independently of concomitant Toll or imd pathway activation. Our data failed to confirm a role of the PGRP-SA and GNBP1 Pattern Recognition Receptors for phagocytosis of S. aureus. The Drosophila scavenger receptor Eater mediates the phagocytosis by hemocytes or S2 cells of E. faecalis and S. aureus, but not of M. luteus. In the case of M. luteus and E. faecalis, but not S. aureus, decreased survival due to defective phagocytosis could be compensated for by genetically enhancing the humoral immune response. Our results underscore the fundamental importance of both cellular and humoral mechanisms in Drosophila immunity and shed light on the balance between these two arms of host defense depending on the invading pathogen.


Technical note: Method for improving precision of in-parlor milk meters and adjusting milk weights for stall effects.
Milk yield is a fundamental observation in most dairy experiments and is commonly determined using integrated milk meters that measure milk weight as the cow is being milked. These meters are heavily used in a harsh environment and often are not regularly calibrated, so calibration errors and mechanical problems may create artificial variation in milk weight data. Additionally, direct calibration by collection of milk in a bucket is difficult and imperfect because the use of the bucket may affect yield recorded by the milk meter. The objective of this work was to define a method to easily check parlor meter precision and adjust milk weight values for variation between individual stalls in a parlor. Because most cows are milked in a different stall at each milking, it has been proposed that stall deviations that represent the fixed effect of stall on milk weight could be statistically determined. Individual milk weights from 14 milkings across 7 d from approximately 200 cows were collected from the Penn State dairy farm, which is equipped with a double-10 herringbone parlor with an Afimilk 2000 milking system (S.A.E. Afikim, Afikim, Israel). Milk yield was measured automatically by in-line flow through milk meters (Afi 200; S.A.E. Afikim). The effect of stall on milk weight was modeled using a mixed model that included the fixed effect of stall and the random effects of day, milking time, and cow. First, stall deviations were calculated as the stall least squares means (LSM) minus the average LSM to identify malfunctioning meters requiring service (e.g., deviation exceeding 1 kg). A correction factor for each stall was then generated by dividing the LSM of each stall by the average LSM. Milk yields were then corrected by multiplying the meter weight value by the correction factor. To determine the effect of the correction, raw and corrected meter values were compared with weight of milk collected in a bucket (n = 3/stall). The corrected values had a 5% greater coefficient of determination than raw meter values (0.89 vs. 0.84) and had a lower average percent difference from the bucket milk weight compared with raw meter values (12.6% vs. 13.5%). The method was then used in 3 experiments with 121, 140, and 683 milk yield observations. In all data sets, correcting milk weights slightly improved model fit and had minimal effect on model term standard errors. However, this validation was completed in a parlor where the method was routinely used to identify stalls requiring service; the effect of stall corrections is expected to be larger in parlors without frequent monitoring. Stall deviations are expected to be due predominantly to calibration of the meter but also could be due to differences in pulsation or other stall-specific factors that result in a change in milk yield. It is important to account for these other sources of milk weight variation that are unrelated to treatment. Modeling the effect of stall is a simple, convenient, and low-cost method to monitor and improve milk meter precision and functionality and can be used to reduce artificial variation and experimental error.


Optimization of sample preparation for culture-independent sequencing of Bordetella pertussis.
Bordetella pertussis, the aetiological agent of whooping cough, is re-emerging globally despite widespread vaccination. B. pertussis is highly infectious and, prior to vaccination programmes, was the leading cause of infant mortality. The WHO estimated that over 600 000 deaths are prevented annually by pertussis vaccination, but B. pertussis infection was still responsible for over 63 000 deaths globally in 2013. The re-emergence of B. pertussis has been linked to strains with inactive or absent major virulence factors included in vaccines such as pertactin, pertussis toxin and filamentous haemagglutinin. Thus, the molecular surveillance of currently circulating strains is critical in understanding and controlling B. pertussis. Such information provides data on strains to inform control measures and the identification of future vaccine antigens. Current surveillance and typing methods for B. pertussis rely on the availability of clinical isolates. However, since the 1990s, the majority of pertussis cases have been diagnosed by PCR, where an isolate is not needed. The rapid decline in the availability of B. pertussis isolates impacts our ability to monitor this infection. The growing uptake of next-generation sequencing (NGS) has offered the opportunity for culture-independent genome sequencing and typing of this fastidious pathogen. Therefore, the objective of the study was to optimize respiratory sample preparation, independent of culture, in order to type B. pertussis using NGS. The study compared commercial depletion kits and specimen-processing methods using selective lysis detergents. The goal was to deplete human DNA, the major obstacle for sequencing a pathogen directly from a clinical sample. Samples spiked with a clinically relevant amount of B. pertussis were used to provide comparison between the different methods. Commercial depletion kits including the MolYsis, Qiagen Microbiome and NEBNext Kits were tested. Previously published methods, for Saponin and TritonX-100, were also trialled as a depletion. The ratio of B. pertussis to human DNA was determined by real-time PCR for ERV3 and IS481 (as markers of human and B. pertussis DNA, respectively), then samples were sequenced using the Illumina NextSeq 500 platform. The number of human and B. pertussis sequenced reads were then compared between treatments. The results showed that commercial kits reduced the human DNA present, but also reduced the concentration of target B. pertussis. However, selective lysis with Saponin treatment resulted in almost undetectable levels of human DNA, with minimal loss of target B. pertussis DNA. Sequencing read depth improved five-fold in reads to B. pertussis. Our investigation delivered a potential protocol that will enable the public health laboratory surveillance of B. pertussis in the era of culture-independent testing.


Dioxin-like and non-dioxin-like toxic effects of polychlorinated biphenyls (PCBs): implications for risk assessment.
Polychlorinated biphenyls (PCBs) are persistent, bioaccumulative, and toxic contaminants in the environment. Individual PCB congeners exhibit different physicochemical properties and biological activities that result in different environmental distributions and toxicity profiles. The variable composition of PCB residues in environmental matrices and their different mechanisms of toxicity complicate the development of scientifically based regulations for the risk assessment. In this article various approaches for the assessment of risks of PCBs have been critically examined. Recent developments in the toxic equivalency factor (TEF) approach for the assessment of toxic effects due to dioxin-like PCBs have been examined. PCB exposure studies that describe non-dioxin-like toxic effects, particularly neurobehavioral effects and their effective doses in animals were compiled. A comparative assessment of effective doses for dioxin-like and non-dioxin-like effects by PCBs has been made to evaluate the relative significance of non-ortho-and ortho-substituted PCBs in risk assessment. Using mink as an example, relative merits and implications of using TEF and total PCB approaches for assessing the potential for toxic effects in wildlife was examined. There are several advantages and limitations associated with each method used for PCB risk assessment. Toxic effects due to coplanar PCBs occur at relatively smaller concentrations than those due to non-dioxin-like PCBs and therefore the TEF approach derives the risk assessment of PCBs, in the environment. The need for the refinement of TEF approach for more accurate assessment of risks is discussed.


Chromatin-bound PCNA complex formation triggered by DNA damage occurs independent of the ATM gene product in human cells.
Proliferating cell nuclear antigen (PCNA), a processivity factor for DNA polymerases delta and epsilon, is involved in DNA replication as well as in diverse DNA repair pathways. In quiescent cells, UV light-induced bulky DNA damage triggers the transition of PCNA from a soluble to an insoluble chromatin-bound form, which is intimately associated with the repair synthesis by polymerases delta and epsilon. In this study, we investigated the efficiency of PCNA complex formation in response to ionizing radiation-induced DNA strand breaks in normal and radiation-sensitive Ataxia telangiectasia (AT) cells by immunofluorescence and western blot techniques. Exposure of normal cells to gamma-rays rapidly triggered the formation of PCNA foci in a dose-dependent manner in the nuclei and the PCNA foci (40-45%) co-localized with sites of repair synthesis detected by bromodeoxyuridine labeling. The chromatin-bound PCNA gradually declined with increasing post-irradiation times and almost reached the level of unirradiated cells by 6 h. The PCNA foci formed after gamma-irradiation was resistant to high salt extraction and the chromatin association of PCNA was lost after DNase I digestion. Interestingly, two radiosensitive primary fibroblast cell lines, derived from AT patients harboring homozygous mutations in the ATM gene, displayed an efficient PCNA redistribution after gamma-irradiation. We also analyzed the PCNA complex induced by a radiomimetic agent, Bleomycin (BLM), which produces predominantly single- and double-strand DNA breaks. The efficiency and the time course of PCNA complex induced by BLM were identical in both normal and AT cells. Our study demonstrates for the first time that the ATM gene product is not required for PCNA complex assembly in response to DNA strand breaks. Additionally, we observed an increased interaction of PCNA with the Ku70 and Ku80 heterodimer after DNA damage, suggestive of a role for PCNA in the non-homologous end-joining repair pathway of DNA strand breaks.


Could We See the End of Tobacco Being Sold in Bars and Pubs in New Zealand?
Disallowing the sale of tobacco wherever alcohol is consumed is one policy option to help achieve Smokefree 2025. This study aimed to investigate the prevalence of selling tobacco in New Zealand (NZ) on-license premises and explore attitudes toward the sale of tobacco. A sample of managers of on-license premises were asked by telephone about the importance of tobacco to their business, advantages and disadvantages of selling tobacco, and the impact of not being able to sell tobacco in the future. Logistic and linear regression analyses were used to investigate associations between on-license characteristics and selling status and importance scores, respectively. Of on-license premises, 6.5% (95% CI: 5.3, 8.0) sold tobacco; 17.4% (95% CI: 14.0, 21.4) of hotels, 17.5% (95% CI: 13.8, 21.9) of taverns, and 1.3% (95% CI: 0.6, 3.2) of restaurants. Both retailer type and population density were associated with selling status. On-licenses were more likely to rate tobacco as "unimportant" (51.7%) to their business than "important" (30.0%), although premises where the closest tobacco retailer was at least 1 km away were associated with a higher score. Similar proportions of businesses were opposed to (45.7%) and supported (47.2%) the policy of removing all tobacco sales from on-license premises. Few on-license premises in NZ sell tobacco. Most retailers would support transitioning out of selling tobacco before the 2025 Smokefree goal, and they believed ending sales of tobacco would not negatively affect their business. However, businesses and customers in rural areas may be more affected than others. Many countries have tobacco-free goals, with several still developing their endgame strategies to achieve these goals. This study provides NZ and other jurisdictions with evidence useful in the development of such strategies. Having on-license alcohol retailers transition out of sales of tobacco would contribute to a reduction in tobacco availability. Moreover, the results of this study suggest that, in part due to declining tobacco sales and increased thefts, such a policy is likely to have the support of retailers. Policy developers should note, however, the potential for different impacts where the distance to the closest tobacco retailer is over 1 km or in rural areas.


Recombinant 43-kDa USF binds to DNA and activates transcription in a manner indistinguishable from that of natural 43/44-kDa USF.
USF is a cellular factor involved in the transcriptional regulation of several cellular and viral promoters. Purified USF from HeLa cells (HeLa USF) consists of 43- and 44-kDa polypeptides which show independent binding to a specific DNA element. A cDNA encoding the 43-kDa species has been previously cloned. We show here that the purified form of bacterially expressed 43-kDa USF (i) exists in solution as a dimer whose formation is greatly favored under reducing conditions, (ii) binds to its cognate DNA sequence in a manner indistinguishable from that of HeLa USF, and (iii) is as efficient as HeLa USF in stimulating transcription from target promoters in a reconstituted cell-free system. Additional data indicate that the 44-kDa component of HeLa USF is immunologically unrelated to the 43-kDa polypeptide but is associated with it in HeLa cell extracts. These results suggest that the 43-kDa component possesses an intrinsic DNA binding and transcriptional activation potential and that the 44-kDa USF component of the natural USF complex may have some regulatory role.


Microbial flora of pecan meat.
Microorganisms found associated with commercially shelled pecan meats are numerous and varied. No bacteria and only two fungal microorganisms, Aspergillus clavatus and Tricothecium species, were found on aseptically shelled pecans.


Retinoids in Acne Management: Review of Current Understanding, Future Considerations, and Focus on Topical Treatments
Acne vulgaris is the most common skin condition affecting adolescents and young adults with a tremendous psychosocial impact. Its pathogenic hallmarks include follicular dyskeratosis, increased sebum production, and inflammation induced by Cutibacterium (formerly Propionibacterium) acnes within the follicle. Retinoids, derived from vitamin A, are the mainstays of acne treatment given they address the key pathogenic pathways of acne. Retinoids exert their effects through the binding of their nuclear receptors leading to downstream biological effects. The understanding of retinoid pharmacology has increased the diversity of retinoids with now both natural and synthetic retinoids available for use. For acne, retinoids can be administered both topically in a variety of formulations and combinations as well as systemically. With judicious use, this class of medication is well tolerated and very efficacious in managing acne. Furthermore, there is evidence showing its role in improving and preventing one of the most challenging post-acne changes, atrophic acne scarring. With a promising topical retinoid, trifarotene, on the horizon, the acne armamentarium will be further broadened to better manage acne and its related sequelae. J Drugs Dermatol. 2018;17(12 Suppl):s51-55


A Novel Bifunctional μOR Agonist and σ1R Antagonist with Potent Analgesic Responses and Reduced Adverse Effects.
Bifunctional ligands possessing both μOR agonism and σ1R antagonism have shown promise in producing strong analgesic effects with reduced opioid-related side effects. However, the μOR agonism activity of most dual ligands diminishes compared with classical opioids, raising concern about their effectiveness in managing nociceptive pain. In this study, a new class of dual μOR agonist/σ1R antagonist was reported. Through structure-activity relationship analyses, we identified the optimal compound, 4x, which displayed picomolar μOR agonism activity (EC50: 0.6 ± 0.2 nM) and good σ1R inhibitory activity (Ki: 363.7 ± 5.6 nM) with excellent selectivity. Compound 4x exhibited robust analgesic effects in various pain models, with significantly reduced side effects. Importantly, compound 4x also possessed good safety profiles and no abnormalities were observed in biological parameters even under a high dosage. Our findings suggest that 4x may be a promising lead compound for developing safer opioids and warrants further in-depth studies.


Influence of BDNF Val66Met on the relationship between cardiorespiratory fitness and memory in cognitively normal older adults.
Higher cardiorespiratory fitness has been associated with better cognitive function in older adults; yet, this relationship demonstrates a degree of variability across the older adult population. Thus, it is hypothesised that variation in genetic factors may influence the relationship between fitness and cognitive health. One such genetic factor is the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, which has previously been shown to moderate the relationship between self-reported physical activity and memory performance. In this study we aim to investigate the interaction between BDNF Val66Met polymorphism and objectively-measured cardiorespiratory fitness on performance on tasks assessing verbal and visuospatial memory. Data from ninety-nine cognitively normal men and women aged 60-80 years were used. Fitness was assessed by peak oxygen consumption, and verbal and visuospatial memory were evaluated using well-validated measures. Participants were categorised into: lower-fit Met carriers, higher-fit Met carriers, lower-fit Val/Val, or higher-fit Val/Val. Higher-fit individuals performed better on a task assessing visuospatial memory, compared with lower-fit individuals. Furthermore, an interaction between BDNF Val66Met and fitness was observed in terms of visuospatial memory performance on a continuous paired associate learning task; whereby lower-fit Met carriers performed 1 standard deviation worse than higher-fit Met carriers. No differences were observed between the higher-fit and lower-fit Val/Val homozygotes. Future intervention studies should evaluate the effect of structured exercise on cognitive health between BDNF Val66Met carriers and Val/Val homozygotes.


Utilization of an automated ECG interpretation system in an ambulatory health service.
A computerized ECG interpretation system was incorporated into a large ambulatory health care service. The central unit has several terminals located at various regional cardiological clinics. In each clinic 80--120 ECG's are taken daily, of which 56% are interpreted as normal tracings. The interpretation system is currently utilized to separate automatically normal from abnormal tracings. Normal tracings are not re-checked by a cardiologist and the report is delivered directly to the family physician. In order to evaluate the reliability of the computer interpretation of normal ECG's (i.e., the percent of false-negative readings), 500 tracings interpreted by the program as normal were selected at random and read independently by three cardiologists. It was found that in 4.6% of the cases additional remarks were supplemented to the computer statement by at least one of the cardiologists. Most of the computer-cardiologist disagreements were of limited clinical importance. It was concluded that this system could be used as an effective tool for simultaneously processing ECG's from several remote locations, serving large ambulatory populations. By using the assistance of the computer system, marked reduction in cardiologists' time and cost could be achieved.


Laboratory detection of macro-aspartate aminotransferase: case report and evaluation of the PEG-precipitation method.
Chronic elevated AST without other signs of liver disease, cardiac or skeletal abnormalities, is suggestive for macro-AST. Laboratory detection can be performed by gel filtration chromatography, ultrafiltration or precipitation with polyethylene glycol (PEG). A healthy 27 year-old female was referred because of chronic elevated AST (116-704U/L) without other abnormalities. Macro-AST positivity was suspected since AST was no longer measurable in the supernatant of a serum sample (<3U/L) after PEG precipitation. Optimization of this method included analysis of proteins and lipids precipitated, testing the effect of different PEG concentrations and centrifugation times. 25% (m/v) PEG solution gave the most reliable results. No significant difference was seen between 10 and 30 min centrifugation time. A reference range was obtained by analysis of 31 normal patient samples (mean % PEG precipitation activity 35.1% with 95% confidence limits of 14.5-62.5%). Retrospective analysis of 1371 patient samples with elevated AST revealed one other positive patient sample. Early recognition of macro-AST, proven by simple PEG precipitation, can avoid time-consuming and invasive investigations.


Human intestinal epithelial cells express receptors for platelet-activating factor.
The intestinal epithelium produces and responds to cytokines and lipid mediators that play a key role in the induction and regulation of mucosal inflammation. The lipid mediator platelet-activating factor (PAF) can be produced and degraded by the human intestinal epithelium and is known to mediate a range of proinflammatory and other biological effects in the intestinal mucosa. In the studies herein, we assessed whether or not human intestinal epithelial cells express cell surface or intracellular PAF receptors (PAF-R), whether expression of these receptors can be regulated, and whether human intestinal epithelial cells respond to PAF. Several human colon epithelial cell lines (HT-29, Caco-2, T84, HCT-8, HCA-7, I407, and LS-174T) were shown by RT-PCR to constitutively express mRNA for PAF-R. In addition, PAF-R expression was demonstrated by immunoblot analysis and PAF-R was shown to be constitutively expressed on the cell surface of several of these cell lines, as assessed by flow cytometry. PAF-R expression by human colon epithelial cells was upregulated by stimulation with retinoic acid but not by stimulation with PAF, proinflammatory agonists (tumor necrosis factor-alpha, interleukin-1, interferon-gamma), or transforming growth factor-alpha. PAF-R on intestinal epithelial cells were functional, as PAF stimulation of the cells increased tyrosine phosphorylation of several cellular proteins, including proteins of 75 and 125 kDa, and this response was blocked by a PAF-R antagonist. Consistent with the findings using cell lines, PAF-R were also constitutively expressed by normal human colon and small intestinal epithelium in vivo, as shown by immunohistology. The constitutive and regulated expression of functional PAF-R by human intestinal epithelium suggests PAF produced by the intestinal epithelial cells or cells underlying the epithelium has autocrine or paracrine effects on intestinal epithelial cells.


Paraguay's Path Toward the Simplification of Procedures in the Approval of GE Crops.
Agricultural biotechnology was first regulated in Paraguay in 1997. The first update to the country's regulatory framework came in 2012, motivated by the need to keep up with current technologies. As part of this process, in late 2012, the Paraguayan Ministry of Agriculture (MAG) joined the Partnership for Biosafety Risk Assessment and Regulation, led by ILSI Research Foundation. The purpose of the program was the development of capacity building activities. As a result, the regulatory authorities in Paraguay incorporated the problem formulation approach to environmental risk assessment into their regulatory processes, leading to improved efficiency, with more timely decisions. Shifting to a problem formulation-based decision-making system was not straightforward, since practice and experience are always required to make professional risk assessors. Despite the continuity of approvals, there was a lag in the response time reflected in the number of events approved. During 2019, a simplified approval procedure for events that have been assessed by sound and experienced regulatory systems was introduced. Acceptance of third-country assessments can allow regulatory systems to make better use of their human, financial, and institutional resources, and stimulate inter-agency cooperation. In this work we aim to present the recent evolution of the regulatory system in Paraguay toward the establishment of a simplified procedure for GE crops that have been already assessed by sound and experienced regulatory systems, taking into account several scientific criteria. Concepts such as the familiarity, history of safe use, substantial equivalence, transportability, problem formulation, and the use of the consensus documents, developed by Organization for Economic Co-operation and Development (OECD), Food and Agriculture Organization of the United Nations (FAO), World Health Organization (WHO) and other institutions, favors the acceptance of decision documents issued by third countries. This requires the commitment of governments to support the stability of the institutions responsible for the regulatory implementation and also encourages countries to put work into the preparation and publication of decision documents, which are the basis for the commercialization of GE events.


A technical framework for costing health workforce retention schemes in remote and rural areas.
Increasing the availability of health workers in remote and rural areas through improved health workforce recruitment and retention is crucial to population health. However, information about the costs of such policy interventions often appears incomplete, fragmented or missing, despite its importance for the sound selection, planning, implementation and evaluation of these policies. This lack of a systematic approach to costing poses a serious challenge for strong health policy decisions. This paper proposes a framework for carrying out a costing analysis of interventions to increase the availability of health workers in rural and remote areas with the aim to help policy decision makers. It also underlines the importance of identifying key sources of financing and of assessing financial sustainability.The paper reviews the evidence on costing interventions to improve health workforce recruitment and retention in remote and rural areas, provides guidance to undertake a costing evaluation of such interventions and investigates the role and importance of costing to inform the broader assessment of how to improve health workforce planning and management. We show that while the debate on the effectiveness of policies and strategies to improve health workforce retention is gaining impetus and attention, there is still a significant lack of knowledge and evidence about the associated costs. To address the concerns stemming from this situation, key elements of a framework to undertake a cost analysis are proposed and discussed. These key elements should help policy makers gain insight into the costs of policy interventions, to clearly identify and understand their financing sources and mechanisms, and to ensure their sustainability.


Estimating The Effects Of Health Insurance And Other Social Programs On Poverty Under The Affordable Care Act.
The effects of health insurance on poverty have been difficult to ascertain because US poverty measures have not taken into account the need for health care and the value of health benefits. We developed the first US poverty measure to include the need for health insurance and to count health insurance benefits as resources available to meet that need-in other words, a health-inclusive poverty measure. We estimated the direct effects of health insurance benefits on health-inclusive poverty for people younger than age sixty-five, comparing the impacts of different health insurance programs and of nonhealth means-tested cash and in-kind benefits, refundable tax credits, and nonhealth social insurance programs. Private health insurance benefits reduced poverty by 3.7 percentage points. Public health insurance benefits (from Medicare, Medicaid, and Affordable Care Act premium subsidies) accounted for nearly one-third of the overall poverty reduction from public benefits. Poor adults with neither children nor a disability experienced little poverty relief from public programs, and what relief they did receive came mostly from premium subsidies and other public health insurance benefits. Medicaid had a larger effect on child poverty than all nonhealth means-tested benefits combined.


Trans-Balance: Reducing demographic disparity for prediction models in the presence of class imbalance.
Risk prediction, including early disease detection, prevention, and intervention, is essential to precision medicine. However, systematic bias in risk estimation caused by heterogeneity across different demographic groups can lead to inappropriate or misinformed treatment decisions. In addition, low incidence (class-imbalance) outcomes negatively impact the classification performance of many standard learning algorithms which further exacerbates the racial disparity issues. Therefore, it is crucial to improve the performance of statistical and machine learning models in underrepresented populations in the presence of heavy class imbalance. To address demographic disparity in the presence of class imbalance, we develop a novel framework, Trans-Balance, by leveraging recent advances in imbalance learning, transfer learning, and federated learning. We consider a practical setting where data from multiple sites are stored locally under privacy constraints. We show that the proposed Trans-Balance framework improves upon existing approaches by explicitly accounting for heterogeneity across demographic subgroups and cohorts. We demonstrate the feasibility and validity of our methods through numerical experiments and a real application to a multi-cohort study with data from participants of four large, NIH-funded cohorts for stroke risk prediction. Our findings indicate that the Trans-Balance approach significantly improves predictive performance, especially in scenarios marked by severe class imbalance and demographic disparity. Given its versatility and effectiveness, Trans-Balance offers a valuable contribution to enhancing risk prediction in biomedical research and related fields.


A Pan-Cancer and Polygenic Bayesian Hierarchical Model for the Effect of Somatic Mutations on Survival.
We built a novel Bayesian hierarchical survival model based on the somatic mutation profile of patients across 50 genes and 27 cancer types. The pan-cancer quality allows for the model to "borrow" information across cancer types, motivated by the assumption that similar mutation profiles may have similar (but not necessarily identical) effects on survival across different tissues of origin or tumor types. The effect of a mutation at each gene was allowed to vary by cancer type, whereas the mean effect of each gene was shared across cancers. Within this framework, we considered 4 parametric survival models (normal, log-normal, exponential, and Weibull), and we compared their performance via a cross-validation approach in which we fit each model on training data and estimate the log-posterior predictive likelihood on test data. The log-normal model gave the best fit, and we investigated the partial effect of each gene on survival via a forward selection procedure. Through this we determined that mutations at TP53 and FAT4 were together the most useful for predicting patient survival. We validated the model via simulation to ensure that our algorithm for posterior computation gave nominal coverage rates. The code used for this analysis can be found at https://github.com/sarahsamorodnitsky/Pan-Cancer-Survival-Modeling.git, and the results are summarized at http://ericfrazerlock.com/surv_figs/SurvivalDisplay.html.


Live-cell imaging of dual-labeled Golgi stacks in tobacco BY-2 cells reveals similar behaviors for different cisternae during movement and brefeldin A treatment.
In plant cells, the Golgi apparatus consists of numerous stacks that, in turn, are composed of several flattened cisternae with a clear cis-to-trans polarity. During normal functioning within living cells, this unusual organelle displays a wide range of dynamic behaviors such as whole stack motility, constant membrane flux through the cisternae, and Golgi enzyme recycling through the ER. In order to further investigate various aspects of Golgi stack dynamics and integrity, we co-expressed pairs of established Golgi markers in tobacco BY-2 cells to distinguish sub-compartments of the Golgi during monensin treatments, movement, and brefeldin A (BFA)-induced disassembly. A combination of cis and trans markers revealed that Golgi stacks remain intact as they move through the cytoplasm. The Golgi stack orientation during these movements showed a slight preference for the cis side moving ahead, but trans cisternae were also found at the leading edge. During BFA treatments, the different sub-compartments of about half of the observed stacks fused with the ER sequentially; however, no consistent order could be detected. In contrast, the ionophore monensin resulted in swelling of trans cisternae while medial and particularly cis cisternae were mostly unaffected. Our results thus demonstrate a remarkable equivalence of the different cisternae with respect to movement and BFA-induced fusion with the ER. In addition, we propose that a combination of dual-label fluorescence microscopy and drug treatments can provide a simple alternative approach to the determination of protein localization to specific Golgi sub-compartments.


Radiological and instrumental neutron activation analysis determined characteristics of size-fractionated fly ash.
The concentration of trace elements and radionuclides in fly ash particles of different size can exhibit significant variation, due to the various processes taking place during combustion inside a coal-fired power plant. An investigation of this effect has been performed by analyzing samples of fly ash originating in two different coal-fired power plants, after separation into size fractions by sieving. The samples were analyzed by gamma-ray spectrometry, including low-energy techniques, radon exhalation measurement and instrumental neutron activation analysis for the determination of Al, As, Ga, K, La, Na, Mn, Mg, Sr, Sc, and V. Variations are observed in the results of various samples analyzed, while the activity balances calculated from the results of individual size fractions are consistent with those of the raw ash samples. Correlations among the radionuclides examined are also observed, while individual nuclide behavior varies between the two types of fly ash examined.


Diabetic emergencies - ketoacidosis, hyperglycaemic hyperosmolar state and hypoglycaemia.
Diabetic ketoacidosis (DKA), hyperglycaemic hyperosmolar state (HHS) and hypoglycaemia are serious complications of diabetes mellitus that require prompt recognition, diagnosis and treatment. DKA and HHS are characterized by insulinopaenia and severe hyperglycaemia; clinically, these two conditions differ only by the degree of dehydration and the severity of metabolic acidosis. The overall mortality recorded among children and adults with DKA is <1%. Mortality among patients with HHS is ~10-fold higher than that associated with DKA. The prognosis and outcome of patients with DKA or HHS are determined by the severity of dehydration, the presence of comorbidities and age >60 years. The estimated annual cost of hospital treatment for patients experiencing hyperglycaemic crises in the USA exceeds US$2 billion. Hypoglycaemia is a frequent and serious adverse effect of antidiabetic therapy that is associated with both immediate and delayed adverse clinical outcomes, as well as increased economic costs. Inpatients who develop hypoglycaemia are likely to experience a long duration of hospital stay and increased mortality. This Review describes the clinical presentation, precipitating causes, diagnosis and acute management of these diabetic emergencies, including a discussion of practical strategies for their prevention.


Epidemiological relevance of dogs for the prevention of Toxoplasma gondii, Neospora caninum and Leptospira spp.
This study evaluated the seroprevalence of Toxoplasma gondii, Neospora caninum and Leptospira spp. in dogs from Foz do Iguaçu, Paraná, Brazil. Indirect immunofluorescent antibody test was used to detect antibodies anti-T.gondii and anti-N. caninum. Immunoenzymatic assay and microscopic serum agglutination were used for screening antibodies anti-T.gondii and anti-Leptospira spp., respectively. The results were: 67.02% of the samples reactive for T.gondii and 1.38% for N. caninum, both without statistically significant variables. For Leptospira spp. the results indicated seroprevalence of 23.11%. The analysis of the variables without distinction of serovar showed association for intrinsic characteristics as breed, age, nutritional status and dog category. The extrinsic variables as city region and access to the street presented association (p<0.05). The most prevalent serovars were: Canicola 59.47%; Bratislava 13.07% and Butembo 15.68%. Variables that make up the adjusted multiple analysis model using Leptospira spp. were: age, breed and nutritional status; serovar Canicola, sex, nutritional status and area (p<0.05); serovar Bratislava, lymphadenomegaly and presence of fleas (p<0.05). Given the results obtained, dogs can be used as sentinels for toxoplasmosis and leptospirosis in Foz do Iguaçu and other cities with similar outcomes. In addition, preventive measures should be taken by health authorities because they are zoonoses and humans are also at risk.


Intrinsic and extrinsic regulation of innate immune receptors.
Pattern recognition receptors (PRRs) in innate immune cells play a pivotal role in the first line of host defense system. PRRs recognize pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) to initiate and regulate innate and adaptive immune responses. PRRs include Toll-like receptors (TLRs), RIG-I-like receptors (RLRs) and NOD-like receptors (NLRs), which have their own features in ligand recognition and cellular location. Activated PRRs deliver signals to adaptor molecules (MyD88, TRIF, MAL/TIRAP, TRAM, IPS-1) which act as important messengers to activate downstream kinases (IKK complex, MAPKs, TBK1, RIP-1) and transcription factors (NF-κB, AP-1, IRF3), which produce effecter molecules including cytokines, chemokines, inflammatory enzymes, and type I interferones. Since excessive PRR activation is closely linked to the development of chronic inflammatory diseases, the role of intrinsic and extrinsic regulators in the prevention of over- or unnecessary activation of PRRs has been widely studied. Intracellular regulators include MyD88s, SOCS1, TOLLIP, A20, and CYLD. Extrinsic regulators have also been identified with their molecular targets in PRR signaling pathways. TLR dimerization has been suggested as an inhibitory target for small molecules such as curcumin, cinnamaldehyde, and sulforaphane. TBK1 kinase can be a target for certain flavonoids such as EGCG, luteolin, quercetin, chrysin, and eriodictyol to regulate TRIF-dependent TLR pathways. This review focuses on the features of PRR signaling pathways and the therapeutic targets of intrinsic and extrinsic regulators in order to provide beneficial strategies for controlling the activity of PRRs and the related inflammatory diseases and immune disorders.


Insulin and glucagon regulate the activation of two distinct membrane-bound cyclic AMP phosphodiesterases in hepatocytes.
Glucagon (10 nM) caused a transient elevation of intracellular cyclic AMP concentrations, which reached a peak in around 5 min, and slowly returned to basal values in around 30 min. When 1 mM-3-isobutyl-1-methylxanthine (IBMX) was present, this process yielded a Ka of 1 nM for glucagon. The addition of insulin (10 nM) after 5 min exposure to glucagon (10 nM) caused intracellular cyclic AMP concentrations to fall dramatically, attaining basal values within 10 min. The regulation of this process was dose-dependent, exhibiting a Ka of 0.4 nM for insulin. If insulin and glucagon were added together to hepatocytes, then insulin decreased the magnitude of the cyclic AMP response to glucagon. IBMX (1 mM) prevented insulin antagonizing the action of glucagon in both of these instances. A gentle homogenization procedure followed by a rapid subcellular fractionation of hepatocytes on a Percoll gradient was developed. This was used to resolve subcellular membrane fractions and to identify cyclic AMP phosphodiesterase activity in both membrane and cytosol fractions. Glucagon and insulin only affected the activity of two distinct membrane-bound species, a plasma-membrane enzyme and a 'dense vesicle' enzyme. Glucagon (10 nM), insulin (10 nM), IBMX (1 mM), dibutyryl cyclic AMP (10 microM) and cholera toxin (1 microgram/ml) all elicited the activation of the 'dense vesicle' enzyme. The plasma-membrane enzyme was not activated by glucagon, IBMX or dibutyryl cyclic AMP, although insulin and cholera toxin both led to its activation. The degree of activation of the plasma-membrane enzyme produced by insulin was increased in the presence of IBMX or dibutyryl cyclic AMP. Glucagon pretreatment (5 min) of hepatocytes blocked the ability of insulin to activate the plasma-membrane enzyme. The activity state of these phosphodiesterases is discussed in relation to the observed changes in intracellular cyclic AMP concentrations. It is suggested that insulin exerts its action on the plasma-membrane phosphodiesterase through a mechanism involving a guanine nucleotide-regulatory protein.


Conformational changes of Aβ (1-42) monomers in different solvents.
Amyloid proteins are known to be the main cause of numerous degenerative and neurodegenerative diseases. In general, amyloids are misfolded from monomers and they tend to have β-strand formations. These misfolded monomers are then transformed into oligomers, fibrils, and plaques. It is important to understand the forming mechanism of amyloids in order to prevent degenerative diseases to occur. Aβ protein is a highly noticeable protein which causes Alzheimer's disease. It is reported that solvents affect the forming mechanism of Aβ amyloids. In this research, Aβ1-42 was analyzed using an all-atom MD simulation with the consideration of effects induced by two disparate solvents: water and DMSO. As a result, two different conformation changes of Aβ1-42 were exhibited in each solvent. It was found that salt-bridge of Asp23 and Lys28 in Aβ1-42 was the key for amyloid folding based on the various analysis including hydrogen bond, electrostatic interaction energy and salt-bridge distance. Since this salt-bridge region plays a crucial role in initiating the misfolding of Aβ1-42, this research may shed a light for studies related in amyloid folding and misfolding.


A novel model to study the dorsolateral migration of melanoblasts.
Melanocytes derived from pluripotent neural crest cells migrate initially in the dorsolateral pathway between the ectoderm and dermomyotome. To understand the role of specific proteins involved in this cell migration, we looked for a cellular model that mimics the in vivo behavior of melanoblasts, and that allows functional studies of their migration. We report here that wild-type embryonic stem (ES) cells are able to follow the ventral and dorsolateral neural crest pathways after being grafted into chicken embryos. By contrast, a mutant ES cell line deficient for beta1 integrin subunits, proteins involved in cell-extracellular interactions, had a severely impaired migratory behavior. Interestingly, ES cells deficient for Kit, the tyrosine kinase receptor for the stem cell factor (SCF), behaved similarly to wild-type ES cells. Thus, grafting mouse ES cells into chicken embryos provides a new cellular system that allows both in vitro and in vivo studies of the molecular mechanisms controlling dorsolateral migration.


Scoping review of Paleolithic dietary patterns: a definition proposal.
The Paleolithic diet (PaleoDiet) is an allegedly healthy dietary pattern inspired by the consumption of wild foods and animals assumed to be consumed in the Paleolithic era. Despite gaining popularity in the media, different operational definitions of this Paleolithic nutritional intake have been used in research. Our hypothesis is that specific components used to define the PaleoDiet may modulate the association of this diet with several health outcomes. We comprehensively reviewed currently applied PaleoDiet scores and suggested a new score based on the food composition of current PaleoDiet definitions and the theoretical food content of a staple dietary pattern in the Paleolithic age. In a PubMed search up to December 2019, fourteen different PaleoDiet definitions were found. We observed some common components of the PaleoDiet among these definitions although we also found high heterogeneity in the list of specific foods that should be encouraged or banned within the PaleoDiet. Most studies suggest that the PaleoDiet may have beneficial effects in the prevention of cardiometabolic diseases (type 2 diabetes, overweight/obesity, CVD and hyperlipidaemias) but the level of evidence is still weak because of the limited number of studies with a large sample size, hard outcomes instead of surrogate outcomes and long-term follow-up. Finally, we propose a new PaleoDiet score composed of eleven food items, based on a high consumption of fruits, nuts, vegetables, fish, eggs and unprocessed meats (lean meats); and a minimum content of dairy products, grains and cereals, and legumes and practical absence of processed (or ultra-processed) foods or culinary ingredients.


Advancing Nutrition and Dietetics Research in Global Food and Nutrition Security: A Roundtable Proceedings Report.
Food and nutrition security remains a relevant issue globally, impacting nutritional status and other health outcomes. This is further complicated by various environmental factors that impact stable access to, availability of, and utilization of nutritious foods. Nutrition and dietetics practitioners play an important role in the identification and treatment of food and nutrition security and are also well positioned to advance research that can support food and nutrition security solutions. To address this important issue, the Academy of Nutrition and Dietetics' Council on Research convened a Global Food and Nutrition Security Research Task Force (Task Force). To leverage existing information and expertise in this area and identify the need for future evidence, the Task Force hosted a virtual roundtable with key internal and external stakeholders. This 2-day event included discussions on research gaps, potential entry points for nutrition and dietetics practitioners, and important equity considerations in the area of food and nutrition security research. The identified research gaps included the need for standardized terminology for consistent data collection, the need for validated screening and assessment tools that can be used across settings and also assess diet quality, additional translational and implementation science research, multi-sectoral and multi-pronged approaches, interdisciplinary collaboration with community partners, incorporation of research into policy development, and additional evidence on food systems approaches to target food and nutrition security. To more clearly identify the entry points for practitioners, five examples from various countries were included to identify food and nutrition security issues and how nutrition and dietetics practitioners can be involved in research to address food and nutrition security. The Task Force would like this information to inform a research agenda and be leveraged by the larger scientific community to drive future funding and research opportunities for food and nutrition professionals on this topic.


Fluid-gas exchange and photocoagulation after vitrectomy. Indications, technique, and results.
We describe the indications, complications, and results of postvitrectomy fluid-gas exchange and laser photocoagulation for management of complicated vitreoretinal disease. Indications include proliferative vitreoretinopathy, vitreous opacities associated with proliferative diabetic retinopathy, giant retinal tear, recurrent rhegmatogenous retinal detachment, and trauma. Eyes treated with 50% sulfur hexafluoride gas rather than sterile air demonstrated a higher intraocular pressure on the first postexchange day, which was not a significant source of disease. There was no statistically significant difference in retinal reattachment between eyes treated with gas and those treated with air. Fluid-gas exchange in eyes with partial or total retinal detachment resulted in total or partial retinal reattachment, with the macula attached in 82% of cases within the first 48 hours following exchange. Final reattachment rate, with a mean follow-up of 8.9 months (range, six to 36 months), was 55%. In eyes with proliferative vitreoretinopathy, the combination of postoperative argon or krypton laser photocoagulation with fluid-gas exchange was associated with a final reattachment rate of 75%. Postoperative fluid-gas exchange and photocoagulation appear to be safe and effective advances in the treatment of complicated vitreoretinal diseases requiring vitrectomy.


Effect of feed treatment and exogenous estrogen and progestogen on puberty and lambing rates in ewe lambs.
Four hundred seventy-four ewe lambs (5 to 6 mo of age) were assigned within breed to two postweaning feed treatments; 1 = alfalfa pellets ad libitum and 2 = alfalfa pellets plus 20% barley or wheat ad libitum. Ten days prior to the start of breeding, approximately one-half of the ewe lambs within each feed treatment were treated with a single injection of 2.5 mg of estradiol valerate and 1.5 mg of norgestomet and implanted with 3 mg of norgestomet for 8 d. At the start of breeding, fertile Suffolk rams were fitted with marking harnesses and penned with ewe lambs; evidence of estrus and breeding was determined on a weekly basis by visual examination for breeding marks. In the second year of the study, 7 to 13 d after recording estrous activity, all marked ewe lambs were bled; and blood was assayed for progesterone. In 1983, 60% of the ewe lambs showed estrus and 11% lambed compared with 48% exhibiting estrus and 30% lambing in 1984 (P less than .01). More (P less than .01) ewe lambs on feed treatment 1 displayed estrus, but more (P less than .05) lambed in the feed treatment 2 group. Steroid treatment resulted in more (P less than .01) ewe lambs showing estrus but fewer lambing (P less than .01). Examination of progesterone concentrations for evidence of ovulation and corpus luteum development indicated that treatment with steroids caused a large percentage of ewe lambs to exhibit estrus. However, many of these failed to develop a corpus luteum and become pregnant.(ABSTRACT TRUNCATED AT 250 WORDS)


Elevational variation in density dependence in a subtropical forest.
Density-dependent mortality has been recognized as an important mechanism that underpins tree species diversity, especially in tropical forests. However, few studies have attempted to explore how density dependence varies with spatial scale and even fewer have attempted to identify why there is scale-dependent differentiation. In this study, we explore the elevational variation in density dependence. Three 1-ha permanent plots were established at low and high elevations in the Heishiding subtropical forest, southern China. Using data from 1200 1 m(2) seedling quadrats, comprising of 200 1 m(2) quadrats located in each 1-ha plot, we examined the variation in density dependence between elevations using a generalized linear mixed model with crossed random effects. A greenhouse experiment also investigated the potential effects of the soil biota on density-dependent differentiation. Our results demonstrated that density-dependent seedling mortality can vary between elevations in subtropical forests. Species found at a lower elevation suffered stronger negative density dependence than those found at a higher elevation. The greenhouse experiment indicated that two species that commonly occur at both elevations suffered more from soilborne pathogens during seed germination and seedling growth when they grew at the lower elevation, which implied that soil pathogens may play a crucial role in density-dependent spatial variation.


Artificial ecosystem selection.
Artificial selection has been practiced for centuries to shape the properties of individual organisms, providing Darwin with a powerful argument for his theory of natural selection. We show that the properties of whole ecosystems can also be shaped by artificial selection procedures. Ecosystems initiated in the laboratory vary phenotypically and a proportion of the variation is heritable, despite the fact that the ecosystems initially are composed of thousands of species and millions of individuals. Artificial ecosystem selection can be used for practical purposes, illustrates an important role for complex interactions in evolution, and challenges a widespread belief that selection is most effective at lower levels of the biological hierarchy.


Comprehensive analysis of nuclear export of herpes simplex virus type 1 tegument proteins and their Epstein-Barr virus orthologs.
Morphogenesis of herpesviral virions is initiated in the nucleus but completed in the cytoplasm. Mature virions contain more than 25 tegument proteins many of which perform both nuclear and cytoplasmic functions suggesting they shuttle between these compartments. While nuclear import of herpesviral proteins was shown to be crucial for viral propagation, active nuclear export and its functional impact are still poorly understood. To systematically analyze nuclear export of tegument proteins present in virions of Herpes simplex virus type 1 (HSV1) and Epstein-Barr virus (EBV), the Nuclear EXport Trapped by RAPamycin (NEX-TRAP) was applied. Nine of the 22 investigated HSV1 tegument proteins including pUL4, pUL7, pUL11, pUL13, pUL21, pUL37d11, pUL47, pUL48 and pUS2 as well as 2 out of 6 EBV orthologs harbor nuclear export activity. A functional leucine-rich nuclear export sequence (NES) recognized by the export factor CRM1/Xpo1 was identified in six of them. The comparison between experimental and bioinformatic data indicates that experimental validation of predicted NESs is required. Mutational analysis of the pUL48/VP16 NES revealed its importance for herpesviral propagation. Together our data suggest that nuclear export is an important feature of the herpesviral life cycle required to co-ordinate nuclear and cytoplasmic processes.