Chemical carcinogenesis.
Understanding the relationship of chemicals to carcinogenesis has progressed significantly since the initial observations of Hill and Pott in the 1700's. Distinguishing between DNA-reactive chemicals and those which increase cancer risk by increasing cell proliferation has been a major breakthrough in delineating overall mechanisms. Competing processes for activation versus inactivation of chemicals occur at many levels, including metabolism, DNA repair, and cellular repair processes. These processes can be affected by other agents to decrease carcinogenesis (chemoprevention). Increasing knowledge of the multiple steps of carcinogenesis is leading to improved methods for screening chemicals for carcinogenic activity and for regulatory decision making. Improvements in assessment of modes of action involved in animal and in vitro models have led to more rational approaches to assessing relevance to humans. The advent of genomics and high-throughput technologies have contributed to investigations of mechanisms and is beginning to impact development of better methods for screening chemicals. Based on developments in basic research, epidemiology, and astute clinical observations, the major risk factors and etiologic agents have been identified for a majority of cancers, which is beginning to lead to methods to decrease cancer incidence overall and identify targets for early detection and treatment.


Activity of cannabis in relation to its delta'-trans-tetrahydro-cannabinol content.
1 Conditions have been worked out for a reliable estimation of the cataleptic activity of delta'-trans-tetrahydrocannabinol (THC) after oral administration to mice, using the ring test over a period of 6 h. 2 By this method, the activity of cannabis herb and 5 crude fractions were measured against THC; at the same time the THC contents were determined chemically. 3 The B/C ratio (biological activity divided by chemical assay) was calculated for each. With cannabis herb the value was 3.3 and with extracts prepared with ethanol or 70% ethanol the values ranged from 3.2 to 7.1, indicating that in all samples the activity was much higher than would be expected from their THC content. 4. The cannabinoids were completely extracted from a sample of herb using petroleum spirit and the marc examined for a possible synergist. Surprisingly, it contained a powerful inhibitor of the action of THC, which could be restored by intraperitoneal prostaglandin E2 (3 microgram/kg). Some crude fractions had inhibitory activities about 10 times that of aspirin. 5 In contrast, the petroleum spirit extract (referred to in 4) had a surprisingly high B/C ratio of 23, indicating that a powerful synergist of THC activity is present. 6 The net effect of the herb and ethanol extracts is probably due to a balance of synergist and inhibitor.


IMPACT-Restart: the influence of COVID-19 on postoperative mortality and risk factors associated with SARS-CoV-2 infection after orthopaedic and trauma surgery.
The primary aim of this study was to assess the independent association of the coronavirus disease 2019 (COVID-19) on postoperative mortality for patients undergoing orthopaedic and trauma surgery. The secondary aim was to identify factors that were associated with developing COVID-19 during the postoperative period. A multicentre retrospective study was conducted of all patients presenting to nine centres over a 50-day period during the COVID-19 pandemic (1 March 2020 to 19 April 2020) with a minimum of 50 days follow-up. Patient demographics, American Society of Anesthesiologists (ASA) grade, priority (urgent or elective), procedure type, COVID-19 status, and postoperative mortality were recorded. During the study period, 1,659 procedures were performed in 1,569 patients. There were 68 (4.3%) patients who were diagnosed with COVID-19. There were 85 (5.4%) deaths postoperatively. Patients who had COVID-19 had a significantly lower survival rate when compared with those without a proven SARS-CoV-2 infection (67.6% vs 95.8%, p < 0.001). When adjusting for confounding variables (older age (p < 0.001), female sex (p = 0.004), hip fracture (p = 0.003), and increasing ASA grade (p < 0.001)) a diagnosis of COVID-19 was associated with an increased mortality risk (hazard ratio 1.89, 95% confidence interval (CI) 1.14 to 3.12; p = 0.014). A total of 62 patients developed COVID-19 postoperatively, of which two were in the elective and 60 were in the urgent group. Patients aged > 77 years (odds ratio (OR) 3.16; p = 0.001), with increasing ASA grade (OR 2.74; p < 0.001), sustaining a hip (OR 4.56; p = 0.008) or periprosthetic fracture (OR 14.70; p < 0.001) were more likely to develop COVID-19 postoperatively. Perioperative COVID-19 nearly doubled the background postoperative mortality risk following surgery. Patients at risk of developing COVID-19 postoperatively (patients > 77 years, increasing morbidity, sustaining a hip or periprosthetic fracture) may benefit from perioperative shielding. Cite this article: Bone Joint J 2020;102-B(12):1774-1781.


Metopism: a Study of the Persistent Metopic Suture.
Metopism, the persistence of the metopic suture in adulthood, is a clinically significant radiographic finding. In addition to masquerading as a fracture of the frontal bone, a persistent metopic suture may be associated with other clinically significant anatomical variations including frontal sinus abnormalities. Several geographically and craniofacially distinct populations have yet to be assessed for the prevalence of metopism. This study aimed to determine the prevalence of metopic sutures in adult crania of diverse populations among which scant research exists. A total of 505 adult crania were examined for the presence of a metopic suture. A total of 13 (2.57%) demonstrated metopism. Among subpopulations, metopism was present in 8.06% (5:62) of European crania, 15.38% (2:13) of East Asian crania, 2.20% (2:91) of Egyptian crania, and 2.86% (1:35) of Bengali crania. Metopism was also found in 1 Chilean, Roman, and Tchuktchi cranium, respectively. Metopism was not seen in crania from individuals of African (non-Egyptian) descent (0:62), Peruvians (0:144), Malayans (0:23), or Mexicans (0:23). Among sexes, metopism was present in 3.77% (8:212) of females and 1.79% (5:279) of males. The prevalence of metopism differs between populations and sexes. The results of this study provide anthropological, developmental, and clinical insight with regard to metopism.


Novel COX11 Mutations Associated with Mitochondrial Disorder: Functional Characterization in Patient Fibroblasts and Saccharomyces cerevisiae.
Genetic defects in the nuclear encoded subunits and assembly factors of cytochrome c oxidase (mitochondrial complex IV) are very rare and are associated with a wide variety of phenotypes. Biallelic pathogenic variants in the COX11 protein were previously identified in two unrelated children with infantile-onset mitochondrial encephalopathies. Through comprehensive clinical, genetic and functional analyses, here we report on a new patient harboring novel heterozygous variants in COX11, presenting with Leigh-like features, and provide additional experimental evidence for a direct correlation between COX11 protein expression and sensitivity to oxidative stress. To sort out the contribution of the single mutations to the phenotype, we employed a multi-faceted approach using Saccharomyces cerevisiae as a genetically manipulable system, and in silico structure-based analysis of human COX11. Our results reveal differential effects of the two novel COX11 mutations on yeast growth, respiration, and cellular redox status, as well as their potential impact on human protein stability and function. Strikingly, the functional deficits observed in patient fibroblasts are recapitulated in yeast models, validating the conservation of COX11's role in mitochondrial integrity across evolutionarily distant organisms. This study not only expands the mutational landscape of COX11-associated mitochondrial disorders but also underscores the continued translational relevance of yeast models in dissecting complex molecular pathways.


Investigation of the genotoxic potential of the marine biotoxins azaspiracid 1-3.
Azaspiracids (AZAs) are the most recently discovered group of biotoxins and are the cause of azaspiracid shellfish poisoning (AZP) in humans. To date over thirty analogues have been identified. However, toxicological studies of AZAs are limited due to the lack of availability of toxins and toxin standards. Most data available are on acute toxicity and there are no data available on genotoxicity of AZAs. This study presents an integrated approach investigating the genotoxic potential of AZA1-3 in cell culture systems using the Comet assay combined with assays to provide information on possible apoptotic processes, cytotoxicity and changes in cell number. Results demonstrate a time and dose dependent increase in DNA fragmentation in most cell lines, indicating a genotoxic effect of AZA1-3. However, a significant reduction in cell number and a clear shift from early to late apoptosis was observed for all analogues in Jurkat T cells and HepG-2 cells; CaCo-2 cells did not show a clear apoptotic profile. Late apoptotic/necrotic cells correlate well with the percentage of tail DNA for all analogues in all three cell lines. All data taken together indicate that AZA1-3 is not genotoxic per se and demonstrate apoptotic/necrotic processes to be involved to some extent in AZAs toxicity. The sensitivities of cell lines and the different potencies of AZA1-3 are in agreement with the literature available. The order of sensitivity for all three AZAs tested in the present study is, in increasing order, CaCo-2 cells < HepG-2 cells < Jurkat T cells. The order of potency of AZA1-3 varies among the cell lines.


[Current forms of persistent chronic hallucinatory psychosis].
The persistency of the "Psychose Hallucinatoire Chronique" (P.H.C.) in the french psychiatric nosology can be understood through a study of the history of ideas, since the beginning of the century, about chronic delusions. Ancient authors' descriptions (Ballet, Clérambault) agree with a semiological reality often observed now. The present clinical-looking of the "P.H.C." allows to establish that: the mechanisms used by the delusion have been little altered through time, the themes taken are impregnated by late scientific discoveries and with present socio-political context, the frequency of evolution to encysted forms have increased with modern chemical therapeutics. The function of hallucinatory delusion often appears to make up for successive frustrations, sexual and affective insufficiency or sensorial isolations, and then avoids too painful suffering to the patient. To day, the attitude of psychiatrist towards hallucinated delirious patients is centred on the discovery of the personality and the biography of the patient rather than on the complete analysis of the semiology obtained in spite of reticence.


Effects of a worksite program to improve the cardiovascular health of female health care workers.
Reducing cardiovascular risk for female health care workers supports self-care and facilitates a culture of health promotion. We examined the effect of individualized motivational communications on risk and measured program participation at a busy hospital, utilizing cardiac rehabilitation resources. Women (40-65 years old) who self-identified as having increased cardiovascular risk and ready for change were randomly assigned to weekly motivational counseling or control. All participants were offered classes (weight/diet, stress, exercise, and smoking cessation) and gym access. Physical and perceptual measures were recorded before and after the 6-month program to measure change. Followup 1 year later measured current weight, stress, and physical activity. Participants (n = 57) ranked weight as their greatest concern (42%). Compared with control, the intervention group resulted in greater: weight loss (7.2 vs 3.8 pounds); stress reduction (6.5 vs 4.7; Cohen stress scale); and exercise days per week (1.4 vs 1.2). Differences were not statistically significant in this small sample, but all changes consistently favored the intervention. Program participation was low, as was participation in the 1-year followup, although those responding indicated maintenance or further improvement. These consistent and positive findings are promising but only suggestive because of the small sample size. Future studies should focus on how to get more buy-in from employees, to help insure persistence toward health goals. Study results assisted development of a comprehensive Web-based employee wellness motivational program to address the issues of on-site participation. Attention to health risks in health care workers remains an important area of study.


[Use of radiotherapy in the complex treatment of patients with complicated forms of diabetic angiopathy].
In 140 patients with purulent-necrotic complications of diabetic microangiopathy the results of different methods of treatment were analyzed. High efficacy of antiinflammatory X-ray therapy was confirmed. Application of X-ray therapy in combination with long lasting intraarterial infusions promoted lowering the frequency of high amputation of the extremity conduction.


A mixed polyploid model for linkage analysis in outcrossing tetraploids using a pseudo-test backcross design.
Based on how chromosomes pair at meiosis, the nature of polyploids can be described by bivalent polyploids, multivalent polyploids, and mixed polyploids. In bivalent polyploids, only two chromosomes pair, during which two more similar chromosomes have a higher pairing probability (preferential pairing) than two less similar chromosomes, whereas in multivalent polyploids more than two chromosomes pair at a time, which results in double reduction. Preferential chromosome pairings and double reduction affect the frequencies of gamete formation and, therefore, linkage analysis of polymorphic markers in bivalent and multivalent polyploids, respectively. For mixed polyploids, in which both bivalent and multivalent formations occur simultaneously, linkage analysis is affected by both preferential pairings and double reduction. In this study, we develop a hierarchical maximum likelihood model for discerning gamete genotypes derived from different pairing mechanisms and different formation modes. The first-stage model in the hierarchy is formulated to characterize the relative frequencies of bivalent and multivalent pairing configurations in terms of the preferential pairing factor. The second-stage model is derived to rule out identical gamete genotypes into their different formation modes with relative probabilities determined by the recombination fraction. The first-stage pairing mechanism and second-stage formation mode are integrated to provide the simultaneous maximum likelihood estimates of the preferential pairing factor, the frequency of double reduction, and the recombination fraction, by implementing the EM algorithm. We performed extensive simulation studies to demonstrate the statistical properties of our hierarchical model for linkage analysis in tetraploids. The implications of our model for polyploid linkage mapping are discussed.


EFFECTS OF TOPICAL TREATMENT WITH EUPHORBIA TIRUCALLI LATEX ON THE SURVIVAL AND INTESTINAL ADHESIONS IN RATS WITH EXPERIMENTAL PERITONITIS.
The use of plants of the family Euphorbiaceae, particularly Euphorbia tirucalli (avelós) has been popularly widespread for treating a variety of diseases of infectious, tumoral, and inflammatory. To demonstrated antimicrobial and immunomodulatory effects of these extracts, evaluating the effect of a topical treatment with an aqueous solution of avelós latex on the survival and on intestinal adhesions in rats with experimental peritonitis. Peritonitis was induced in 24 Wistar rats, that were randomized into four groups of six as follows: (1) Control group (n=6), no treatment; (2) Antibiotic group (n=6), treatment with a single intramuscular dose of antibiotic Unasyn; (3) Saline group (n=6), the abdominal cavity was washed with 0.9% saline; and (4) E.tirucalli group (n=6), the abdominal cavity was washed with E. tirucalli at a concentration of 12 mg/ml. The animals that died were necropsied, and the time of death was recorded. The survivors were killed on postoperative day 11, and necropsy was subsequently performed for evaluation of the intestinal adhesions. Significant differences were observed in the control and antibiotic groups (p<0.01) with respect to the survival hours when compared with the saline and E. tirucalli groups. There was no significant difference (p>0.05) in the survival of animals in the saline andE. tirucalli groups; however, one animal died in the saline group. Necropsy of the animals in the saline and E. tirucalligroups showed strong adhesions resistant to manipulation, between the intestinal loops and abdominal wall. The remaining groups did not show any adhesions. Topical treatment with E. tirucalli latex stimulated an increased formation of intestinal adhesions and prevented the death of all animals with peritonitis.


[Lichen sclerosus and Turner syndrome].
Lichen sclerosus was diagnosed at a young age (19, 22 and 37 years) in three women with Turner syndrome. The oldest of these patients had probably suffered from this disorder for over 20 years. The relatively young age of these three patients is remarkable. This observation also suggests an increased frequency of lichen sclerosus among women with Turner syndrome. Immunological and hormonal factors might explain this association. Early detection of lichen sclerosus is important, as malignant transformation into carcinoma of the vulva may occur. It is advisable to perform regular gynaecological examination as part of the recommended periodic screening of adult women with Turner syndrome.


[Control of Rhipicephalus sanguineus (Latrielle, 1806) (Acari: Ixodidae) in the kennel of the UFMG Veterinary School, Belo Horizonte, Minas Gerais, Brazil].
The present work was aimed at proposing a control measure for Rhipicephalus sanguineus in a naturally infected kennel of 72 m(2) of the UFMG Veterinary School with 25 dogs of different breeds. A sensitivity test to acaricide products was applied in a sample of R. sanguineus. Out of the acaricide products tested: 12.5% Amitraz (product 1); 2% Alfamethrin and 60% Dichlorvos association (product 2); 5% Deltamethrin (product 3) and the association between 77.6% Trichlorfon, 1.0% Coumaphos and 1.0% Cyfluthrin (product 4); only 1 and 4 products showed 100% efficacy. Amitraz (12.5%) was used for controlling R. sanguineus in the surrounding of the kennel, on which four treatments every seven days were carried out in the facilities. For parasitic R. sanguineus, a single topical treatment was used: Flumetrin 1.0% pour-on on all the 25 dogs. This control measure significantly reduced the population of R. sanguineus within the kennel. A slight infestation was observed in the seventh month after treatment. A new application of 12.5% Amitraz was done in the kennel as well as a new topical treatment with Flumetrin 1.0% pour-on on the dogs. The control procedure proposed in the present study was an emergency measure and its effectiveness was checked through environmental surveys throughout a one-year period.


Tuberculous lymphadenitis in Singapore.
An analysis of patients diagnosed as having tuberculous lymphadenitis (the second commonest form of tuberculosis after respiratory tuberculosis) in 1980, was carried out to ascertain the pattern of disease and methods of diagnosis. Of 114 cases so notified, 97 were available for this purpose. Diagnosis was on lymph node biopsy with histological examination and/or bacteriological culture confirmation. Patients with tuberculous lymphadenitis tended to be young (more than 60% below 31 years old), and to have cervical involvement (88.6% of cases). A female preponderance (as in other studies) and a disproportionate number of Indians and Malays (thrice and twice that expected on the basis of their ethnic proportion of the Singapore population) were noted. Only 25 out of 97 biopsied glands were sent for mycobacterial culture by the surgeons and 16 grew niacin positive Mycobacteria tuberculosis. This 64% culture-positive rate is more sensitive and specific than the histological demonstration of acid-fast bacilli (13.4%) in the diagnosis. It must be stressed that the pathologist can only report a picture consistent with or supportive of a diagnosis of tuberculosis and be more confident if acid-fast bacilli are seen microscopically. The diagnosis cannot be absolute except on a positive culture which also identifies typical or atypical mycobacteria and allows drug sensitivity testing. Surgeons removing lymph nodes in patients suspected to have tuberculous lymphadenitis must send these to both the bacteriologist and pathologist, the tissue to the former not being suspended in formalin but saline.


Dimethyl malonate preserves renal and mitochondrial functions following ischemia-reperfusion via inhibition of succinate dehydrogenase.
Acute kidney injury (AKI), often experienced at the intensive care units, is associated with high morbidity/mortality where ischemia-reperfusion injury is a main causative factor. Succinate accumulation during ischemia contributes to the excessive generation of reactive oxygen species at reperfusion. Inhibition of succinate dehydrogenase has been associated with protective outcome in cardiac ischemia-reperfusion after 24h, but the effects on kidney and mitochondrial functions are less well studied. To investigate the therapeutic potential of succinate dehydrogenase inhibition, by using dimethyl malonate (DMM), on kidney and mitochondria functions in a mouse model of AKI. Male C57BL/6J mice were pre-treated with DMM or placebo, i.p. 30min prior to bilateral renal ischemia (20min). After 3-days of reperfusion, glomerular filtration rate (GFR) was calculated from plasma clearance of FITC-inulin. Kidney mitochondria was isolated and mass specific and intrinsic mitochondrial function were evaluated by high resolution respirometry. Kidney sections were stained (i.e., hematoxylin-eosin and TUNEL) and analyzed for histopathological evaluation of injuries and apotosis, respectively. NADPH oxidase activity in kidney and human proximal tubular cell-line (HK2) were measured luminometrically. DMM treatment improved GFR (p < 0.05) and reduced levels of blood urea nitrogen (p < 0.01) compared to untreated animals, which was associated with lower degree of ischemia-reperfusion-induced tubular injuries (P < 0.001) and apoptosis (P < 0.01). These therapeutic renal effects were linked with improved mitochondrial function, both mass-specific and intrinsic. Finally, DMM treatment prevented ischemia-reperfusion-induced NADPH oxidase activity in the kidney (p < 0.001), which was showed also in HK2 cells exposed to hypoxia and reoxygenation (P < 0.01). Inhibition of succinate dehydrogenase with DMM, in conjunction with the ischemia-reperfusion phase, significantly improved both renal and mitochondrial functions. These findings may have clinical implications for future therapeutic strategies to prevent development of AKI and associated adverse complications, especially in high risk hospitalized patients.


When no one has time: measuring the impact of computerization on health care workers.
Technological change is a constant in today's workplace, especially the modern health care workplace. The introduction of electronic health records changes workloads, job demands, interactions with other health care professionals, and work roles-all elements that have previously been noted to increase work stress and impact health. Despite the significant changes that accompany computerization, it is seldom studied as a source of stress. Also, the health effects of computerization within health care have not been extensively studied. This article summarizes the potential environmental impact of computerization on workers, with special reference to health care workers, and suggests ways occupational health nurses can monitor the health consequences of new technology and intervene in case of adverse health impact. In many health care organizations, high work pressure and staff shortages make it impractical, and perhaps impossible, to use standard in-depth research methods to investigate this issue. Therefore, several less obtrusive methods that can be triangulated are suggested as an alternative.


Vitamin D and the syndromes of azotaemic osteodystrophy.
Intestinal malabsorption of calcium and the development of osteomalacia in conservatively treated renal failure is explained by a quantitative deficiency of 1,25-dihydroxycholecalciferol, which also contributes to the development of hypocalcaemia. Excess of 25-hydroxycholecalciferol can substitute for this deficiency. The presence and healing of azotaemic osteomalacia is unrelated to the prevailing plasma [Ca] x [P] product. The data suggest that "vitamin D" acts directly on bone mineralisation, but the claim that this apparent effect is normally due to 25-hydroxycholecalciferol is considered unproven. Most of the phenomena of azotaemic osteodystrophy are encountered in simple vitamin D deficiency; as in that condition, deficiency of 1,25-dihydroxycholecalciferol may be of primary significance in causing secondary hyperparathyroidism in renal failure.


[Transdermal opiates in the treatment of moderate-severe cancer pain. Recommendations for clinical practice].
Although oral morphine is the gold standard in the front-line approach to moderate-severe cancer pain, transdermal opiates are largely used in clinical practice. Aims of our work were to review the evidences of literature supporting these different habits and to suggest an evidence-based criterion to guide clinical research and clinical practice. A systematic review of literature with meta-analysis of the safety data reported in randomized clinical trials comparing slow releasing oral morphine and transdermal opiates was performed using the random effect model. The quality of the evidences supporting the use of the different strategies and the strength of the recommendations was analyzed using the GRADE method. A significant advantage in favor of transdermal opiates was observed for constipation, urinary retention, need of laxative use and patient's preferences; a significant advantage in favor of slow releasing oral morphine was observed for diarrhea and sweating. The quality of the evidences supporting a front-line use of transdermal fentanyl was considered low, while those supporting the use of transdermal buprenorphine was considered very low. For the use oftransdermal fentanyl and for that oftransdermal buprenorphine a weak and a strong recommendation against their us as front-line treatment of moderate-severe cancer pain can be respectively obtained from the literature data. Transdermal opiates represent a safety and effective alternative to oral morphine against cancer pain, but they can not replace oral morphine as the gold standard first-line treatment of moderate-severe cancer pain.


Exact calculation of end-of-outbreak probabilities using contact tracing data.
A key challenge for public health policymakers is determining when an infectious disease outbreak has finished. Following a period without cases, an estimate of the probability that no further cases will occur in future (the end-of-outbreak probability) can be used to inform whether or not to declare an outbreak over. An existing quantitative approach (the Nishiura method), based on a branching process transmission model, allows the end-of-outbreak probability to be approximated from disease incidence time series, the offspring distribution and the serial interval distribution. Here, we show how the end-of-outbreak probability under the same transmission model can be calculated exactly if data describing who-infected-whom (the transmission tree) are also available (e.g. from contact tracing studies). In that scenario, our novel approach (the traced transmission method) is straightforward to use. We demonstrate this by applying the method to data from previous outbreaks of Ebola virus disease and Nipah virus infection. For both outbreaks, the traced transmission method would have determined that the outbreak was over earlier than the Nishiura method. This highlights that collection of contact tracing data and application of the traced transmission method may allow stringent control interventions to be relaxed quickly at the end of an outbreak, with only a limited risk of outbreak resurgence.


Air pollution diffusion simulation and seasonal spatial risk analysis for industrial areas.
The petrochemical industry produces many air pollutants during production, such as airborne particulate matters (PM10 and PM2.5), sulfur oxides, nitrogen oxides, volatile organic compounds, carbon oxides, etc. Petrochemical industrial accidents are more likely to cause major air pollution hazards in a short period. Therefore this study simulated diffusion and performed air pollution spatial risk analysis for potential air pollutants generated by the petrochemical industry using meteorological observation data from 2017 to 2019. The study targets were No. 6 Naphtha Cracker Complex Petrochemical Industrial Park (6NCC) of Formosa Petrochemical Corporation and Taichung Thermal Power Plant (TTPP) in central Taiwan. We used the industrial source complex model short term (ISCST3) air simulation model developed by the US Environmental Protection Agency to simulate pollutant diffusion under different weather conditions and seasons. Air pollution spatial risk was investigated for neighboring hospitals and schools for pollutant emission and diffusion to provide feedback to petrochemical related industry's risk management. Emission areas (6NCC and TTPP) were all in the southwest since the main air pollution accumulation and diffusion is to the northeast during monsoon season (October through March). Air pollution April through September each year is more evenly distributed, with pollutant concentrations low in all directions, approximately half the concentration in winter. Simulated air pollutant concentrations often overlapped with high risk population clusters (schools and hospitals). 6NCC posed little impact on nearby schools throughout the year; whereas TTPP posed relatively low risks to nearby schools and hospitals in summer, with slightly higher risk for Shenren Elementary School in Shengang township, Changhua County in winter. Overall 6NCC posed higher risk for Mailiao and Taixi townships in Yunlin County; whereas the TTPP posed higher risk on Longjing District of Taichung City, Shengang and Xianxi townships in Changhua County, particularly during winter. The results of this study will help the petrochemical industry and public health authority to wider manage air pollution risks.


Decreased growth during therapy with selective serotonin reuptake inhibitors.
There is no information on the effects of selective serotonin reuptake inhibitors (SSRIs) on growth and puberty in children. We examined growth and growth hormone secretion in 4 children treated with SSRIs for various psychiatric disorders. Case study. Four children (3 boys) aged 11.6 to 13.7 years with obsessive-compulsive disorder or Tourette syndrome. Growth, pubertal progression, and hypothalamic pituitary function. The patients were treated with SSRIs for 6 months to 5 years (dosage, 20-100 mg/d). All were regularly examined for changes in height and bone age and for pubertal progression. They also underwent evaluation of somatotrophic axis and hypothalamic-pituitary axis function. All 4 patients had growth attenuation. Three of them exhibited growth retardation at a pubertal stage when a growth spurt was anticipated. Three had a decreased growth hormone response to clonidine hydrochloride stimulation and 2 to both clonidine and glucagon stimulation, and 1 had decreased 24-hour secretion of growth hormone that normalized when therapy was stopped. The rest of the endocrine evaluations were within reference ranges in all patients. At follow-up, 2 patients were being treated with somatropin while continuing SSRI therapy, and the other 2 resumed normal growth after discontinuation of therapy. A decrease in growth rate, possibly secondary to suppression of growth hormone secretion, may occur during SSRI therapy. As the use of this group of drugs is expected to increase in the young age groups, larger studies are warranted to investigate their effect on growth and growth hormone secretion.


Transcription-dependent mobilization of nucleosomes at accessible TCR gene segments in vivo.
Accessibility of chromosomal recombination signal sequences to the RAG protein complex is known to be essential for V(D)J recombination at Ag receptor loci in vivo. Previous studies have addressed the roles of cis-acting regulatory elements and germline transcription in the covalent modification of nucleosomes at Ag receptor loci. However, a detailed picture of nucleosome organization at accessible and inaccessible recombination signal sequences has been lacking. In this study, we have analyzed the nucleosome organization of accessible and inaccessible Tcrb and Tcra alleles in primary murine thymocytes in vivo. We identified highly positioned arrays of nucleosomes at Dbeta, Jbeta, and Jalpha segments and obtained evidence indicating that positioning is established at least in part by the regional DNA sequence. However, we found no consistent positioning of nucleosomes with respect to recombination signal sequences, which could be nucleosomal or internucleosomal even in their inaccessible configurations. Enhancer- and promoter-dependent accessibility was characterized by diminished abundance of certain nucleosomes and repositioning of others. Moreover, some changes in nucleosome positioning and abundance at Jalpha61 were shown to be a direct consequence of germline transcription. We suggest that enhancer- and promoter-dependent transcription generates optimal recombinase substrates in which some nucleosomes are missing and others are covalently modified.


Alterations in the echocardiographic variables of the right ventricle in asymptomatic patients with breast cancer during anthracycline chemotherapy.
Anthracycline-induced cardiotoxicity can reach an irreversible phase; therefore great efforts are made to diagnose it early. As the right ventricle (RV) is smaller than the left, the right side of the heart is probably influenced by anthracycline to a greater extent and in a shorter time. The purpose of the present study was to investigate the early effects of chemotherapy on the right side of the heart. This cross-sectional study was performed in Isfahan University hospitals from August 2014 to December 2015. Subjects were 67 patients with breast cancer who were planned to receive anthracycline for the first time. Echocardiography was performed before administration of anthracycline and 6 months later. Variables included right heart measures (RV end-diastolic dimensions, right atrium length and diameter), RV fractional area change (RVFAC), index of myocardial performance (Tei index), tricuspid annular plane systolic excursion (TAPSE), pulmonary artery systolic pressure, lateral tricuspid annular early and late diastolic velocities, and tissue Doppler diastolic and systolic velocities. Forty-nine of the subjects completed the study. RV end-diastolic diameters and Tei index (0.31 to 0.37) were significantly increased (p<0.001). RVFAC (49.83% to 43.59%) and TAPSE (18.8 to 17.7 mm) were significantly decreased (p<0.001). There was a significant reduction in E (57.06 to 46.59 cm/s, p<0.001), E/A ratio (1.42 to 1.18, p<0.001), E' (16.73 to 12.4 cm/s, p<0.001), E'/A' ratio (1.21 to 0.9, p<0.001) and S' (12.59 to 10.57 cm/s, p<0.001). Systolic pulmonary arterial pressure (20.63 to 22.24 mm Hg, p=0.04) was significantly increased. This study shows a significant decrease in RV systolic and diastolic function during chemotherapy for 6 months. These reductions are in the normal range and can probably be considered an early indicator of anthracycline-induced cardiotoxicity.


Eye Protection in ENT Practice During the COVID-19 Pandemic.
There is a lack of evidence-based guidelines with regard to eye protection for aerosol-generating procedures in otolaryngology practice. In addition, some recommended personal protective equipment (PPE) is not compatible with commonly used ENT equipment. This study aims to investigate the degree of eye protection that commonly used PPE gives. Simulation model. Simulation laboratory. A custom-built setup was utilized to simulate the clinical scenario of a patient cough in proximity of a health care worker. A system that sprays a xanthan-fluorescein mixture was set up and calibrated to simulate a human cough. A mannequin with cellulose paper placed on its forehead, eyes, and mouth was fitted with various PPE combinations and exposed to the simulated cough. The degree of contamination on the cellulose papers was quantified with a fluorescent microscope able to detect aerosols ≥10 µm. When no eye protection was worn, 278 droplets/aerosols reached the eye area. The use of the surgical mask with an attached upward-facing shield alone resulted in only 2 droplets/aerosols reaching the eye area. In this experiment, safety glasses and goggles performed equally, as the addition of either brought the number of droplets/aerosols reaching the eye down to 0. When used with an upward-facing face shield, there was no difference in the eye protection rendered by safety goggles or glasses in this study. Safety glasses may be considered a viable alternative to safety goggles in aerosol-generating procedures.


What's buzzing on your feed? Health authorities' use of Facebook to combat Zika in Singapore.
In 2016, Singapore grappled with one of the largest Zika outbreaks in Southeast Asia. This study examines the use of Facebook for Zika-related outreach by the Ministry of Health (MOH) and the National Environmental Agency (NEA) from March 1, 2015, to September 1, 2016, and public response to this effort. Despite nearly equivalent outreach, MOH's Facebook posts received more likes (µ = 3.49) and shares (µ = 30.11), whereas NEA's posts received more comments (µ = 4.55), with NEA posting mostly on prevention (N = 30) and MOH on situational updates (N = 24). Thematic analyses identified prevention-related posts as garnering the most likes (N = 1277), while update-related posts were most shared (N = 1059) and commented upon (N = 220). Outreach ceased briefly for 2 months after Singapore's first imported case of Zika, but increased following the outbreak of locally transmitted cases in August 2016. Public engagement was significantly higher during Zika compared with prior haze and dengue outbreaks. The results indicate the value of Facebook as a tool for rapid outreach during infectious disease outbreaks, and as a "listening" platform for those managing the situation. We discuss implications for public health communication research and policy.


Active site mutations and substrate inhibition in human sulfotransferase 1A1 and 1A3.
Human SULT1A1 is primarily responsible for sulfonation of xenobiotics, including the activation of promutagens, and it has been implicated in several forms of cancer. Human SULT1A3 has been shown to be the major sulfotransferase that sulfonates dopamine. These two enzymes shares 93% amino acid sequence identity and have distinct but overlapping substrate preferences. The resolution of the crystal structures of these two enzymes has enabled us to elucidate the mechanisms controlling their substrate preferences and inhibition. The presence of two p-nitrophenol (pNP) molecules in the crystal structure of SULT1A1 was postulated to explain cooperativity at low and inhibition at high substrate concentrations, respectively. In SULT1A1, substrate inhibition occurs with pNP as the substrate but not with dopamine. For SULT1A3, substrate inhibition is found for dopamine but not with pNP. We investigated how substrate inhibition occurs in these two enzymes using molecular modeling, site-directed mutagenesis, and kinetic analysis. The results show that residue Phe-247 of SULT1A1, which interacts with both p-nitrophenol molecules in the active site, is important for substrate inhibition. Mutation of phenylalanine to leucine at this position in SULT1A1 results in substrate inhibition by dopamine. We also propose, based on modeling and kinetic studies, that substrate inhibition by dopamine in SULT1A3 is caused by binding of two dopamine molecules in the active site.


Functional neuroimaging using ultrasonic blood-brain barrier disruption and manganese-enhanced MRI.
Although mice are the dominant model system for studying the genetic and molecular underpinnings of neuroscience, functional neuroimaging in mice remains technically challenging. One approach, Activation-Induced Manganese-enhanced MRI (AIM MRI), has been used successfully to map neuronal activity in rodents. In AIM MRI, Mn(2+) acts a calcium analog and accumulates in depolarized neurons. Because Mn(2+) shortens the T1 tissue property, regions of elevated neuronal activity will enhance in MRI. Furthermore, Mn(2+) clears slowly from the activated regions; therefore, stimulation can be performed outside the magnet prior to imaging, enabling greater experimental flexibility. However, because Mn(2+) does not readily cross the blood-brain barrier (BBB), the need to open the BBB has limited the use of AIM MRI, especially in mice. One tool for opening the BBB is ultrasound. Though potentially damaging, if ultrasound is administered in combination with gas-filled microbubbles (i.e., ultrasound contrast agents), the acoustic pressure required for BBB opening is considerably lower. This combination of ultrasound and microbubbles can be used to reliably open the BBB without causing tissue damage. Here, a method is presented for performing AIM MRI by using microbubbles and ultrasound to open the BBB. After an intravenous injection of perflutren microbubbles, an unfocused pulsed ultrasound beam is applied to the shaved mouse head for 3 minutes. For simplicity, we refer to this technique of BBB Opening with Microbubbles and UltraSound as BOMUS. Using BOMUS to open the BBB throughout both cerebral hemispheres, manganese is administered to the whole mouse brain. After experimental stimulation of the lightly sedated mice, AIM MRI is used to map the neuronal response. To demonstrate this approach, herein BOMUS and AIM MRI are used to map unilateral mechanical stimulation of the vibrissae in lightly sedated mice. Because BOMUS can open the BBB throughout both hemispheres, the unstimulated side of the brain is used to control for nonspecific background stimulation. The resultant 3D activation map agrees well with published representations of the vibrissae regions of the barrel field cortex. The ultrasonic opening of the BBB is fast, noninvasive, and reversible; and thus this approach is suitable for high-throughput and/or longitudinal studies in awake mice.


Performance of academically at-risk medical students in a problem-based learning programme: a preliminary report.
Racially segregated schooling, a legacy of Apartheid policies, continues to hamper education in South Africa. Students entering university from suboptimal circumstances are at significant risk of demonstrating poor academic performance and dropping out of their programmes. Attempts to address the educational needs of these students have included the introduction of extended medical programmes at several universities. Such a programme, the Academic Development Programme (ADP), was implemented at the University of Cape Town in 1991. Over the past decade the programme has graduated more than 100 students. Upon implementation of a new problem-based learning (PBL) programme in 2002, the ADP was discontinued and all students were entered directly into the new PBL programme. Students who demonstrate a need for additional academic support by the end of the first semester enter the Intervention Programme for 1 year before proceeding to the second semester of the PBL programme. An interim analysis was performed to compare the retention rates and academic performance of academically at-risk students in the new PBL programme and the ADP. The records of all academically at-risk students entering the ADP (1991-2000) and the new PBL programme (2002) were reviewed. Retention rates for all years of study, and academic performance in the fourth year clerkship courses of the respective programmes were compared. A total of 239 academically at-risk students in the ADP and 43 at-risk students in the new PBL programme were studied. The median retention rates, per year of study, for at-risk students in the PBL programme was significantly better than for at-risk students in the ADP (p<0.02). Academic performance of the at-risk students in all the fourth year clinical clerkship courses of the PBL programme was significantly better than the mean performance over 10 years for at-risk students in the same fourth year courses in the ADP. The introduction of PBL at the University of Cape Town has not had a deleterious effect on the performance of academically at-risk medical students. Interim analysis suggests that retention rates and academic performance in the PBL programme are better than those achieved in the extended traditional programme.


The Role of the European Society of Human Genetics in Delivering Genomic Education.
The European Society of Human Genetics (ESHG) was founded in 1967 as a professional organisation for members working in genetics in clinical practice, research and education. The Society seeks the integration of scientific research and its implementation into clinical practice and the education of specialists and the public in all areas of medical and human genetics. The Society works to do this through many approaches, including educational sessions at the annual conference; training courses in general and specialist areas of genetics; an online resource of educational materials (EuroGEMS); and a mentorship scheme. The ESHG Education Committee is implementing new approaches to expand the reach of its educational activities and portfolio. With changes in technology, appreciation of the utility of genomics in healthcare and the public's and patients' increased awareness of the role of genomics, this review will summarise how the ESHG is adapting to deliver innovative educational activity.


The use of a physiologically based pharmacokinetic model to evaluate deconvolution measurements of systemic absorption.
An unknown input function can be determined by deconvolution using the systemic bolus input function (r) determined using an experimental input of duration ranging from a few seconds to many minutes. The quantitative relation between the duration of the input and the accuracy of r is unknown. Although a large number of deconvolution procedures have been described, these routines are not available in a convenient software package. Four deconvolution methods are implemented in a new, user-friendly software program (PKQuest, http://www.pkquest.com). Three of these methods are characterized by input parameters that are adjusted by the user to provide the "best" fit. A new approach is used to determine these parameters, based on the assumption that the input can be approximated by a gamma distribution. Deconvolution methodologies are evaluated using data generated from a physiologically based pharmacokinetic model (PBPK). The 11-compartment PBPK model is accurately described by either a 2 or 3-exponential function, depending on whether or not there is significant tissue binding. For an accurate estimate of r the first venous sample should be at or before the end of the constant infusion and a long (10 minute) constant infusion is preferable to a bolus injection. For noisy data, a gamma distribution deconvolution provides the best result if the input has the form of a gamma distribution. For other input functions, good results are obtained using deconvolution methods based on modeling the input with either a B-spline or uniform dense set of time points.


Sensory versus motor loci for integration of multiple motion signals in smooth pursuit eye movements and human motion perception.
We have investigated how visual motion signals are integrated for smooth pursuit eye movements by measuring the initiation of pursuit in monkeys for pairs of moving stimuli of the same or differing luminance. The initiation of pursuit for pairs of stimuli of the same luminance could be accounted for as a vector average of the responses to the two stimuli singly. When stimuli comprised two superimposed patches of moving dot textures, the brighter stimulus suppressed the inputs from the dimmer stimulus, so that the initiation of pursuit became winner-take-all when the luminance ratio of the two stimuli was 8 or greater. The dominance of the brighter stimulus could be not attributed to either the latency difference or the ratio of the eye accelerations for the bright and dim stimuli presented singly. When stimuli comprised either spot targets or two patches of dots moving across separate locations in the visual field, the brighter stimulus had a much weaker suppressive influence; the initiation of pursuit could be accounted for by nearly equal vector averaging of the responses to the two stimuli singly. The suppressive effects of the brighter stimulus also appeared in human perceptual judgments, but again only for superimposed stimuli. We conclude that one locus of the interaction of two moving visual stimuli is shared by perception and action and resides in local inhibitory connections in the visual cortex. A second locus resides deeper in sensory-motor processing and may be more closely related to action selection than to stimulus selection.


Procaterol inhibits IL-1beta- and TNF-alpha-mediated epithelial cell eosinophil chemotactic activity.
Theophylline inhibits eosinophilic infiltration into the bronchial wall. It is unknown whether this is mediated by a cyclic adenosine monophosphate (c-AMP)-dependent reduction in eosinophil chemotactic activity (ECA) from bronchial epithelial cells (BEC). Therefore the effect of a beta2-agonist, procaterol and theophylline on the release of ECA from a BEC line, BEAS-2B was evaluated in response to interleukin (IL)-1beta and tumour necrosis factor-alpha (TNF-alpha). ECA was assessed using a blind-well chemotactic chamber, and the release and gene expression of cytokines were evaluated by means of enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction. IL-1beta and TNF-alpha stimulated the release of ECA from BEAS-2B cells in a dose- and time-dependent manner. Procaterol and theophylline directly inhibited eosinophil migration to IL-1beta and TNF-alpha-conditioned medium. The pretreatment of BEAS-2B cells with the same concentrations of procaterol inhibited the release of ECA in a dose-dependent fashion. Anti-IL-8, anti-regulated on activation, normal T-cell expressed and secreted (RANTES), and anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) inhibited ECA. Procaterol inhibited the release of RANTES, GM-CSF and IL-8 in a dose-dependent fashion. The effect of theophylline was less potent. Procaterol augmented cAMP levels in BEAS-2B cells in a time- and dose-dependent manner. The expression of IL-8, RANTES, and GM-CSF messenger ribonucleic acid was not inhibited by procaterol and theophylline. These data indicate that procaterol and theophylline may directly inhibit eosinophil migration and that procaterol may further inhibit the release of eosinophil chemotactic activity from BEAS-2B cells via a cyclic adenosine monophosphate-dependent mechanism. This warrants further studies on the involvement of bronchial epithelial cells in the anti-inflammatory effects of procaterol and theophylline in patients with asthma.


Imaging-histologic discordance after sonographically guided percutaneous breast biopsy: a prospective observational study.
The objective of this study was to determine the frequency of imaging-histologic discordance and to compare the frequency of carcinoma between concordant and discordant lesions in sonographically (US)-guided 14-gauge core needle biopsies (CNBs). From January 2005 to December 2006, we performed US-guided 14-gauge automated CNB on 3339 breast lesions and obtained benign results in 2194 cases. Five radiologists prospectively reviewed the pathologic reports in conjunction with the imaging. We included a total of 1588 lesions that were either excised (n = 658) or followed up for at least 2 years (n = 930) after CNB. We evaluated the rate of discordance and the clinical findings for both discordant and concordant lesions. We also analyzed the clinical and imaging differences between the upgrade and non-upgrade groups. Imaging-histologic discordance was present in 103 of 1588 (6.5%) lesions. The upgrade rate was 6.8% (7/103) in discordant lesions and 0.4% (6/1485) in concordant lesions (p < 0.01). Lesion size, Breast Imaging, Reporting and Data System (BI-RADS) category and the presence or absence of symptoms was statistically significant between the upgrade and non-upgrade groups in discordant cases (p < .05). Imaging-histologic discordance is an indication for excision because it has a higher upgrade rate than concordant lesions.


Continuum theory of gene expression waves during vertebrate segmentation.
The segmentation of the vertebrate body plan during embryonic development is a rhythmic and sequential process governed by genetic oscillations. These genetic oscillations give rise to traveling waves of gene expression in the segmenting tissue. Here we present a minimal continuum theory of vertebrate segmentation that captures the key principles governing the dynamic patterns of gene expression including the effects of shortening of the oscillating tissue. We show that our theory can quantitatively account for the key features of segmentation observed in zebrafish, in particular the shape of the wave patterns, the period of segmentation and the segment length as a function of time.


p53 gene expression in relation to indoor exposure to unvented coal smoke in Xuan Wei, China.
Lung cancer mortality rates in Xuan Wei County, which are among the highest in China, have previously been associated with exposure to indoor emissions from burning smoky coal. To determine if this association is stronger among lung cancer patients with abnormal expression of p53, we performed a population-based case-control study. Ninety-seven newly diagnosed lung cancer patients and 97 controls, individually matched by age, sex, and home fuel type, were enrolled. We used immunocytochemical methods to assess p53 protein accumulation in exfoliated tumor cells isolated from sputum samples. As expected, the amount of lifetime smoky coal use was associated with an overall increase in lung cancer risk. Compared with subjects who used less than 130 tons of smoky coal during their lifetime, the odds ratios (OR) for lung cancer were 1.48 (95% confidence interval [CI], 0.73 to 3.02) for subjects exposed to 130 to 240 tons, and 3.21 (95% CI, 1.23 to 9.03) for subjects who used more than 240 tons of smoky coal (P for trend 0.01). The effect was due almost exclusively to the pattern in women, almost all of whom were nonsmokers. Further, among highly exposed women, the association was substantially larger and achieved statistical significance only among patients with sputum samples that were positive for p53 overexpression (OR, 18.72; 95% CI, 1.77 to 383.38 vs OR, 4.80; 95% CI, 0.66 to 43.87 for p53-negative cases). This study suggests that exposure to the combustion products of smoky coal in Xuan Wei is more strongly associated with women who have lung cancer accompanied by p53 protein overexpression in exfoliated tumor cells.


Validation of the Childhood Family Mealtime Questionnaire in Mexican Adolescents with Obesity and Their Caregivers.
Childhood obesity is a significant public health concern in Mexico, with far-reaching implications for the nation's healthcare system and economy. In light of this challenge, our study sought to validate the Childhood Family Mealtime Questionnaire (CFMQ) in Mexican adolescents living with obesity and their primary caregivers. A sample of 56 adolescents ages 13 to 17 years and their primary caregivers from one pediatric obesity clinic participated in the study. We conducted a comprehensive assessment of the CFMQ's consistency, reliability, and construct validity among all participants. Internal consistency was determined using Cronbach's α, and the questionnaire's reliability was assessed through test-retest and intraclass correlation coefficients. Construct validity was assessed through an exploratory factor analysis. Our findings confirmed strong internal consistency and reliability for both adolescents and caregivers. Construct validity was established through exploratory factor analysis, refining the questionnaire while preserving its original seven dimensions. This validation of the CFMQ highlights its applicability in evaluating family mealtime experiences in this context, providing valuable insights into the dynamics that influence adolescent nutrition and health. The CFMQ proves to be a reliable tool for assessing family mealtime experiences in Mexican adolescents living with obesity and their caregivers who seek care at third-level public hospitals.


Serum RNA Profiling in the 10-Years Period Prior to Diagnosis of Testicular Germ Cell Tumor.
Although testicular germ cell tumor (TGCT) overall is highly curable, patients may experience late effects after treatment. An increased understanding of the mechanisms behind the development of TGCT may pave the way for better outcome for patients. To elucidate molecular changes prior to TGCT diagnosis we sequenced small RNAs in serum from 69 patients who were later diagnosed with TGCT and 111 matched controls. The deep RNA profiles, with on average 18 million sequences per sample, comprised of nine classes of RNA, including microRNA. We found that circulating RNA signals differed significantly between cases and controls regardless of time to diagnosis. Different levels of TSIX related to X-chromosome inactivation and TEX101 involved in spermatozoa production are among the interesting findings. The RNA signals differed between seminoma and non-seminoma TGCT subtypes, with seminoma cases showing lower levels of RNAs and non-seminoma cases showing higher levels of RNAs, compared with controls. The differentially expressed RNAs were typically associated with cancer related pathways. Our results indicate that circulating RNA profiles change during TGCT development according to histology and may be useful for early detection of this tumor type.


n-3 fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits.
Dietary recommendations have been made for n-3 fatty acids, including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) to achieve nutrient adequacy and to prevent and treat cardiovascular disease. These recommendations are based on a large body of evidence from epidemiologic and controlled clinical studies. The n-3 fatty acid recommendation to achieve nutritional adequacy, defined as the amount necessary to prevent deficiency symptoms, is 0.6-1.2% of energy for ALA; up to 10% of this can be provided by EPA or DHA. To achieve recommended ALA intakes, food sources including flaxseed and flaxseed oil, walnuts and walnut oil, and canola oil are recommended. The evidence base supports a dietary recommendation of approximately 500 mg/d of EPA and DHA for cardiovascular disease risk reduction. For treatment of existing cardiovascular disease, 1 g/d is recommended. These recommendations have been embraced by many health agencies worldwide. A dietary strategy for achieving the 500-mg/d recommendation is to consume 2 fish meals per week (preferably fatty fish). Foods enriched with EPA and DHA or fish oil supplements are a suitable alternate to achieve recommended intakes and may be necessary to achieve intakes of 1 g/d.


Improving Weekend Out Of hours Surgical Handover (WOOSH).
An effective surgical handover is imperative to optimise patient care and safety, whilst ensuring progression of clinical management and the delivery of an efficient service. The introduction of full-shift working, as a response to progressive implementation of the European Working Time Directive (EWTD), has placed the spotlight on patient and doctor safety. Effective handover between shifts is vital to protect patient safety and assist doctors with clinical governance. The weekend is a critical point where the transfer of patient care to the ongoing weekend team is efficient, thorough and informative, as this is a point in the patient journey where the patient is the most vulnerable. The weekend team is often not responsible for the management of the patient throughout the week and poor or incomplete information can have disastrous consequences on patient safety. (1,2,3) There is a general consensus and anecdotal evidence that this process is variable, occasionally unsafe or of poor quality, and can be improved. (4,5,6,7,8,9,10,11) However, no standardised format is deemed optimal or available. The aim therefore, was to design and implement a weekend handover proforma, in order to deliver a more efficient and safer system for patient care over the weekend without increasing junior doctor workload. The Weekend Out Of Hours Surgical Handover (WOOSH) form was designed following consultation with medical, nursing and allied health professionals. All staff were instructed how to complete the form, with pre- and post-intervention questionnaires undertaken. The results of the study enforce and advocate the permanent practice of the WOOSH form with 93.33% endorsing the permanent introduction of the form and 100% finding the form useful.


The effect of bran on glucose kinetics and plasma insulin in non-insulin-dependent diabetes mellitus.
Experiments were carried out on two groups of diabetic patients treated (1) by diet alone (group A) and (2) by diet and oral agents (group B), the latter being discontinued 3 days before each test. All patients were tested twice. To measure rates of glucose metabolism, 3H-3-glucose was infused before and during a standard 3-h 50-g oral glucose tolerance test. 14C-1-glucose was added to the glucose solution and the percentage of ingested glucose that appeared in peripheral blood was calculated. Bran improved glucose tolerance only in group B patients by delaying the peripheral appearance of ingested glucose but had no effect on glucose absorption in group A. In contrast, patients in group A showed a marked reduction in their insulin response when bran was mixed with the glucose. Despite this reduction, glucose tolerance, the metabolic clearance rate (MCR) of glucose, and all other rates measured were unaffected by bran. Thus we conclude that in patients adequately controlled by diet alone, the effect of insulin was potentiated when bran was ingested, but the mechanism involved remains obscure.


Increased livestock weight gain from improved water quality in farm dams: A cost-benefit analysis.
Access to water is a critical aspect of livestock production, although the relationship between livestock weight gain and water quality remains poorly understood. Previous work has shown that water quality of poorly managed farm dams can be improved by fencing and constructing hardened watering points to limit stock access to the dam, and revegetation to filter contaminant inflow. Here we use cattle weight gain data from three North American studies to develop a cost-benefit analysis for the renovation of farm dams to improve water quality and, in turn, promote cattle weight gain on farms in south-eastern Australia. Our analysis indicated a strong likelihood of positive results and suggested there may be substantial net economic benefit from renovating dams in poor condition to improve water quality. The average per-farm Benefit-Cost Ratios based on deterministic assumptions was 1.5 for New South Wales (NSW) and 3.0 for Victoria in areas where rainfall exceeds 600mm annually. Our analyses suggested that cattle on farms in NSW and Victoria would need to experience additional weight gain from switching to clean water of at least 6.5% and 1.8% per annum respectively, to break even in present value terms. Monte Carlo simulation based on conservative assumptions indicated that the probability of per-farm benefits exceeding costs was greater than 70%. We recommend localised experiments to assess the impact of improved water quality on livestock weight gain in Australian conditions to confirm these expectations empirically.


Tissue-Specific Dissociation of Diurnal Transcriptome Rhythms During Sleep Restriction in Mice.
Shortened or mistimed sleep affects metabolic homeostasis, which may in part be mediated by dysregulation of endogenous circadian clocks. In this study, we assessed the contribution of sleep disruption to metabolic dysregulation by analysing diurnal transcriptome regulation in metabolic tissues of mice subjected to a sleep restriction (SR) paradigm. Male mice were subjected to 2 × 5 days of SR with enforced waking during the first 6 hours of the light phase. SR and control mice were sacrificed at different time points of the day and RNA preparations from the mediobasal hypothalamus (MBH), liver, and epididymal white adipose tissue (eWAT) were subjected to whole-genome microarray hybridization. Transcriptional rhythms were associated with changes in behavioral and physiological parameters such as sleep, body temperature, and food intake. Rhythm detection was performed with CircWave and transcription profiles were compared by 2-way analysis of variance and t-tests with Benjamini-Hochberg corrections. Clock gene rhythms were blunted in all tissues, while transcriptome regulation was associated with either clock gene expression, sleep patterns, or food intake in a tissue-specific manner. Clock gene expression was associated with apoptosis pathways in the MBH and with tumor necrosis factor alpha signalling in liver. Food intake-associated genes included cilium movement genes in the MBH and lipid metabolism-associated transcripts in liver. In mice, repeated SR profoundly alters behavioral and molecular diurnal rhythms, disrupting essential signalling pathways in MBH, liver, and eWAT, which may underlie the metabolic and cognitive disturbances observed in sleep-restricted humans such as shift workers.


Brain size at birth throughout human evolution: a new method for estimating neonatal brain size in hominins.
An increase in brain size is a hallmark of human evolution. Questions regarding the evolution of brain development and obstetric constraints in the human lineage can be addressed with accurate estimates of the size of the brain at birth in hominins. Previous estimates of brain size at birth in fossil hominins have been calculated from regressions of neonatal body or brain mass to adult body mass, but this approach is problematic for two reasons: modern humans are outliers for these regressions, and hominin adult body masses are difficult to estimate. To accurately estimate the brain size at birth in extinct human ancestors, an equation is needed for which modern humans fit the anthropoid regression and one in which the hominin variable entered into the regression equation has limited error. Using phylogenetically sensitive statistics, a resampling approach, and brain-mass data from the literature and from National Primate Research Centers on 362 neonates and 2802 adults from eight different anthropoid species, we found that the size of the adult brain can strongly predict the size of the neonatal brain (r2=0.97). This regression predicts human brain size, indicating that humans have precisely the brain size expected as an adult given the size of the brain at birth. We estimated the size of the neonatal brain in fossil hominins from a reduced major axis regression equation using published cranial capacities of 89 adult fossil crania. We suggest that australopiths gave birth to infants with cranial capacities that were on average 180cc (95% CI: 158-205cc), slightly larger than the average neonatal brain size of chimpanzees. Neonatal brain size increased in early Homo to 225cc (95% CI: 198-257cc) and in Homo erectus to approximately 270cc (95% CI: 237-310cc). These results have implications for interpreting the evolution of the birth process and brain development in all hominins from the australopiths and early Homo, through H. erectus, to Homo sapiens.


Early diet and growth: impact on ageing.
The modification of ageing by nutritional intervention is well recognised. Post-weaning diet restriction is the only widely reproducible method to slow ageing, but the effects of prenatal and preweaning diet restriction have been less well characterised. There is some evidence that diet restriction instituted in utero or shortly after birth may have an opposite effect and be associated with increased ageing, and recent work suggests that it may shorten lifespan. Interest in this area has been rekindled by the growing body of epidemiological evidence showing that a number of age-related diseases are associated with poor growth and inadequate nutrition in early life. The relevance of this association to structural and functional ageing changes in different systems is now being considered. Work on musculo-skeletal ageing has demonstrated that loss of muscle strength and bone mass is greater in individuals who did not grow well in early life, and a range of studies suggests that maternal, developmental and nutritional factors are important. The underlying mechanisms remain speculative, and it remains to be determined whether they are system-specific or universal throughout the body. A new cohort of subjects aged between 60 and 70 years is being established to investigate how genetic factors interact with growth and nutritional influences to programme musculo-skeletal ageing in later life.


Regulatory Effect of miR497-5p-CCNE1 Axis in Triple-Negative Breast Cancer Cells and Its Predictive Value for Early Diagnosis.
To explore the regulatory role of miR497-5p-CCNE1 axis in triple-negative breast cancer (TNBC) cells and its predictive value for early diagnosis. Cancer tissue and adjacent tissue samples were collected from 86 patients with TNBC.RT-PCR was used to detect the expression of miR497-5p and CCNE1 (target gene) mRNA, determined by biological prediction in tissue and TNBC cells. ROC was used to analyze the diagnostic value of miR497-5p in TNBC. MTT, invasion, and flow cytometry were used to detect the proliferation, invasion, cycle, apoptosis rate, and expression of related proteins of TNBC cells with overexpression of miR497-5p or knockdown of CCNE1. RT-qPCR results showed that miR497-5p levels were significantly downregulated in TNBC tissue and cells, while CCNE1 expression was significantly upregulated, and miR497-5p expression was negatively correlated with that of CCNE1 (P<0.001). ROC analysis showed that the AUC of miR497-5p for TNBC was >0.9, which had better diagnostic value. The cell tests revealed that miR497-5p played a role in tumor inhibition, including inhibiting proliferation and invasion of TNBC cells, blocking the cell cycle, and promoting apoptosis. Bioinformatic prediction and subsequent experiments revealed that CCNE1 was the direct target of miR497-5p. Furthermore, after knocking down the expression of CCNE1 in TNBC cells, the proliferation and invasion of TNBC cells were significantly inhibited, the cell cycle blocked, and the apoptosis rate significantly increased (P<0.001), and expression of the proapoptosis-related proteins Bax and caspase 3 (cleaved) were upregulated, while expression of the antiapoptosis-related protein BCL2 was downregulated (P<0.001). miR497-5p inhibited the proliferation and invasion of TNBC cells by targeting CCNE1, blocked the cell cycle and promoted the apoptosis of TNBC cells, and had better diagnostic value for TNBC. miR497-5p can be used as a new potential target for the treatment of TNBC.


Characterization of novel immunodominant antigens of Mycobacterium tuberculosis.
Seven novel antigens of Mycobacterium tuberculosis, which had previously been identified based on reactivity to sera from patients with tuberculosis, were characterized. Nucleotide sequence analysis of the genes encoding these seven antigens identified one of them as the FtsH and a second as the aminoimidazole ribotide synthase of M. tuberculosis. Antisera raised to the recombinant forms of each of these seven antigens were used to study the distribution of these proteins within mycobacterial species as well as to determine their subcellular localization and hydrophobicity. Four of the seven antigens were conserved only among pathogenic strains of mycobacteria. Of the seven proteins studied, FtsH and a second protein of unknown identity were localized in membranes. Two were cytosolic, while two others, which had a high proline contents, were tightly associated with the cell wall. One protein was secreted. This secreted protein could be identified by serum from a majority of tuberculosis patients but not BCG-vaccinated individuals, suggesting its potential use in the immunodiagnosis of tuberculosis.


Nature and Development of Membrane Systems in Food Vacuoles of Cellular Slime Molds Predatory upon Bacteria.
Hohl, Hans R. (University of Hawaii, Honolulu). Nature and development of membrane systems in food vacuoles of cellular slime molds predatory upon bacteria. J. Bacteriol. 90:755-765. 1965.-During the digestion of bacteria by the myxamoebae of cellular slime molds, systems of concentric lamellae begin to appear within the food vacuoles. Each constituent lamella is a unit membrane of 75 to 85 A thickness. A study of these lamellae in Dictyostelium discoideum and Polysphondylium pallidum reveals that most of them do not represent original membranes of the ingested bacteria but are formed mainly in two ways. (i) After swelling and partial digestion of the bacteria, the first membranes appear adjacent to pre-existing membranes, e.g., the membrane lining the food vacuole and the cytoplasmic membrane surrounding the bacterium. Progressive addition of lamellae leads to the formation of the systems of concentric lamellae. (ii) After digestion of the bacteria has proceeded to a high degree, the concentric lamellae are formed spontaneously from clouds of amorphous material through condensation and orientation of precursor material. The study shows that, in biological systems, unit membranes may be formed from amorphous material through template action of pre-existing membranes, and does not necessarily involve fusion of membrane-bound vesicles.


Dormant Bacillus spores protect their DNA in crystalline nucleoids against environmental stress.
Bacterial spores of the genera Bacillus and Clostridium are extremely resistant against desiccation, heat and radiation and involved in the spread and pathogenicity of health relevant species such as Bacillus anthracis (anthrax) or Clostridium botulinum. While the resistance of spores is very well documented, underlying mechanisms are not fully understood. In this study we show, by cryo-electron microscopy of vitreous sections and particular resin thin section electron microscopy, that dormant Bacillus spores possess highly ordered crystalline core structures, which contain the DNA, but only if small acid soluble proteins (SASPs) are present. We found those core structures in spores of all Bacillus species investigated, including spores of anthrax. Similar core structures were detected in Geobacillus and Clostridium species which suggest that highly ordered, at least partially crystalline core regions represent a general feature of bacterial endospores. The crystalline core structures disintegrate in a period during spore germination, when resistance against most stresses is lost. Our results suggest that the DNA is tightly packed into a crystalline nucleoid by binding SASPs, which stabilizes DNA fibrils and protects them against modification. Thus, the crystalline nucleoid seems to be the structural and functional correlate for the remarkable stability of the DNA in bacterial endospores.


Apoptosis-related proteins and cervical intraepithelial neoplasia in human immunodeficiency virus-seropositive women.
To evaluate the expression of bcl-2, p-53, Ki-67, and apoptosis as evidenced by nuclear DNA fragmentation in cervical biopsies obtained from human immunodeficiency virus (HIV)-seropositive and HIV-seronegative women with a history of intravenous drug abuse. We investigated 109 consecutive cervical biopsies (73 from HIV seropositive and 36 from HIV seronegative patients), including 86 cervical intraepithelial neoplasia (CIN) lesions and 23 normal cervical epithelium. The markers of apoptosis and proliferation were detected using immunostaining methods on paraffin sections. The associations between HIV status and the intensities of immunostaining were tested by univariate and multivariable methods. The severity of CIN correlated directly with the intensities of p-53 (Spearman Rho = 0.19; P = 0.05) and Ki-67 immunostaining (Spearman Rho = 0.46, P < 0.001) and with apoptosis and Bcl-2 expression (chi-square for trend = 10.6 and 3.91 , P < 0.001 and P = 0.048, respectively).After adjustment, by logistic regression analysis, for the potential confounding effect of severity of CIN and Human Papillomavirus (HPV) infection, apoptosis was five times more common in cervical biopsies of HIV seropositive compared to HIV seronegative patients (27 out of 73 as compared to 4 out of 36, adjusted Odds Ratio = 5.0; 95% confidence intervals = 1.56-16.33, P = 0.007). The adjusted odds ratio of increasing p53 immunodetection was significantly higher in biopsies obtained from HIV-seropositive patients compared to HIV seronegative controls (OR = 8.7; 95% confidence intervals = 2.97-25.3, P < 0.0001). Markers of apoptosis such as nuclear DNA fragmentation and p-53 immunoreactivity are more intensely expressed in cervical biopsies of normal and dysplastic epithelium of HIV-seropositive compared to HIV-seronegative women.


Androgen receptor CAG repeats and prostate cancer.
Prostate cancer is the most common nonskin malignancy and the second leading cause of cancer deaths among men in the United States. Prostate cancer ([Mendelian Inheritance in Man 176807]) has a complex etiology; presently, age, ethnicity, and family history are the most consistently reported risk factors associated with disease. Other potential risk and protective factors have also been suggested. Androgen, acting through the androgen receptor (AR) is helpful in preserving the normal function and structure of the prostate. The AR ([Mendelian Inheritance in Man 313700]) is a structurally conserved member of the nuclear receptor superfamily of ligand-activated transcription factors. Androgens, such as testosterone, are strong tumor promoters, and work with the AR to augment the effect of any carcinogens present and stimulate cell division. The CAG repeats encode long glutamine homopolymeric amino acid chains in the amino-terminal domain of the AR gene. The authors focus on CAG repeat length because recent research suggests that men with shorter AR CAG lengths (e.g., < or =22 repeats) are at a greater risk of developing prostate cancer than are those with longer variants. Among populations studied to date, African Americans appear to have the highest frequency of short CAG repeats. Several potential interactions have also been explored, including molecular interactions, androgen deprivation therapy, and prostate-specific antigen expression. CAG repeat length can be determined with high sensitivity and specificity. Presently, there is no recommended population screening for AR CAG repeat length.


The relationship between the Evaluation Tool of Children's Handwriting and teachers' perceptions of handwriting legibility.
The purpose of this study was to investigate the relationship between the Evaluation Tool of Children's Handwriting (ETCH) and teachers perception of handwriting legibility The ETCH was administered to 45 first-grade students with illegible handwriting as reported by their teachers. The teachers completed a teachers questionnaire at the same time to indicate the children's level of handwriting difficulties both in general and in specific tasks that resemble the test tasks of the ETCH. There was no significant relationship between the ETCH scores and the teacher questionnaire scores in either general legibility or task-specific legibility. The ecological validity of the ETCH, in reference to the teachers' perception of handwriting legibility, was not established. Further changes for scoring criteria may be warranted before the ETCH can be used with confidence that the scores obtained are meaningfully related to actual performance in the classroom as determined by teachers.


Altered immune response differentially enhances susceptibility to Cryptococcus neoformans and Cryptococcus gattii infection in mice expressing the HIV-1 transgene.
Cryptococcus neoformans var. grubii is the most frequent cause of AIDS-associated cryptococcosis worldwide, while Cryptococcus gattii usually infects immunocompetent people. To understand the mechanisms which cause differential susceptibility to these cryptococcal species in HIV infection, we established and characterized a model of cryptococcosis in CD4C/HIV(MutA) transgenic (Tg) mice expressing gene products of HIV-1 and developing an AIDS-like disease. Tg mice infected intranasally with C. neoformans var. grubii strain H99 or C23 consistently displayed reduced survival compared to non-Tg mice at three graded inocula, while shortened survival of Tg mice infected with C. gattii strain R265 or R272 was restricted to a single high inoculum. HIV-1 transgene expression selectively augmented systemic dissemination to the liver and spleen for strains H99 and C23 but not strains R265 and R272. Histopathologic examination of lungs of Tg mice revealed large numbers of widely scattered H99 cells, with a minimal inflammatory cell response, while in the non-Tg mice H99 was almost completely embedded within extensive mixed inflammatory cell infiltrates. In contrast to H99, R265 was dispersed throughout the lung parenchyma and failed to induce a strong inflammatory response in both Tg and non-Tg mice. HIV-1 transgene expression reduced pulmonary production of CCL2 and CCL5 after infection with H99 or R265, and production of these two chemokines was lower after infection with R265. These results indicate that an altered immune response in these Tg mice markedly enhances C. neoformans but not C. gattii infection. This model therefore provides a powerful new tool to further investigate the immunopathogenesis of cryptococcosis.


Treatment of Kratom Dependence With Buprenorphine-Naloxone Maintenance.
Use of the unregulated herbal supplement kratom is on the rise in the United States. We present a case series of 2 patients who developed kratom dependence and withdrawal who were successfully transitioned to buprenorphine-naloxone maintenance. Two patients using kratom to self-treat chronic pain after prescription opioids were discontinued presenting to our clinic with evidence of kratom dependence and withdrawal. On examination, both patients showed signs of mild opioid withdrawal. Both patients were successfully transitioned to buprenorphine-naloxone maintenance via home initiation with control of both their opioid withdrawal and chronic pain. Kratom use is on the rise and with increasing evidence of developing opioid-type dependence due to chronic kratom use. This case series shows that buprenorphine can be used to treat kratom dependence and underlying chronic pain that drives it use.


Cone-beam computed tomography for the assessment of root-crown ratios of the maxillary and mandibular incisors in a Korean population.
This retrospective, cross-sectional study aimed to establish reference data for normal crown and root lengths and the root-crown ratios (R/C ratios) for the mature maxillary and mandibular incisors in a Korean population by using cone-beam computed tomography (CBCT). We included 672 Korean patients (141 men and 531 women; mean age, 27.2 ± 7.7 years) who underwent CBCT examinations during various dental treatments. Crown and root lengths and the R/C ratios of the maxillary and mandibular incisors were measured using CBCT data, which were analyzed to detect significant differences between demographic factors as well as sagittal and vertical skeletal or occlusal relationships. Teeth of the same type in each half-arch were symmetrical. The mean R/C ratios varied from 1.1 to 1.2 for the maxillary incisors and from 1.3 to 1.4 for the mandibular incisors. Crown and root lengths were greater in men than in women, regardless of tooth type. Root lengths and R/C ratios for the mandibular incisors were significantly greater in patients with skeletal Class II malocclusion or an excessive overjet than in the other patients. The R/C ratios for the mandibular incisors were lower in patients with an open bite than in those with a normal or deep bite. Moreover, the R/C ratios for the mandibular incisors increased with age. The data obtained in our study can serve as reference values for crown and root lengths and the R/C ratios for the maxillary and mandibular incisors in the Korean population.


Most Jacobsen syndrome deletion breakpoints occur distal to FRA11B.
Recent studies have identified a (CCG)n repeat in the 5' untranslated region of the CBL2 protooncogene (11q23.3) and have demonstrated that expansion of this repeat causes expression of the folate-sensitive fragile site FRA11B. It has also been demonstrated that FRA11B is the site of breakage in some cases of Jacobsen syndrome (JS) involving terminal deletions of chromosome 11q. We report on 2 patients with JS and a 46,XX,del(11)(q23.3) karyotype. In both cases, microsatellite and fluorescence in situ hybridization analyses indicated that the deletion breakpoint was approximately 1.5-3 Mb telomeric to FRA11B. There was no evidence of expansion of the CBL2 (CCG)n repeat in the parents of either patient. The deleted chromosome was of paternal origin in both cases, although it was of maternal origin in the cases reported to be caused by FRA11B. These findings and those in previously reported patients suggest that the breakpoint for most 11q deletions in JS patients is telomeric to FRA11B, which raises the possibility that there may be other fragile sites in 11q23.3 in addition to FRA11B. These findings also support previous evidence that there may be a propensity for breakpoints to differ depending on the parental origin of the deleted chromosome.


Bacterial population dynamics in a meromictic lake.
Polyclonal antibodies against nine different bacteria isolated from Lake Saelenvannet in western Norway were produced, and the population dynamics of these strains in the lake were monitored through two spring seasons by immunofluorescence staining. The total counts of bacteria varied over time and space from 1.5 x 10(6) to 1.5 x 10(7) cells ml-1. The counts of specific bacteria were in the range of 10(3) to 10(4) cells ml-1 or less; in sum, they generally made up less than 1% of the bacterial community. Some populations showed significant changes in abundance, with blooms lasting 1 to 3 weeks. The rate of change (increase and decrease) in abundance during blooms was estimated to be 0.2 to 0.6 day-1. The average virus-to-bacteria ratio was 50, and there was a significant correlation between the abundances of virus and bacteria. Both protozoan grazing and lytic virus infection were assessed as possible mechanisms driving the variations in bacterial population density.


Subcellular distribution of renal tripeptide-releasing exopeptidases active on collagen-like sequences.
The rat kidney cortex was found to contain two N-terminal exopeptidases of the tripeptidyl peptidase (TPP) class. Each required a free N-terminus to catalyze the release of collagen-related (Gly-Pro-X) "triplets." In accordance with their apparent pH optima, activities were routinely determined fluorimetrically at pH 4.0 (TPP 4) and at pH 7.0 (TPP 7) on Gly-Pro-Met-2-naphthylamide. The specific activity in both the homogenate and the classical subfractions was much greater at pH 7 than at pH 4. Subfractionation of the microsomal fraction by equilibrium banding in sucrose did not separate the TPP 4 and TPP 7 activities. The banding density (1.18 g/ml) and the distribution patterns for TPP 7 in the microsomal subfractions, and also in the subfractions of the small lysosomes in the mitochondrial-lysosomal (ML) fraction, demonstrate that TPP 7 is associated with smooth membranes. The TPP 4 and TPP 7 activities were clearly separated during subfractionation of the ML fraction. Rate sedimentation demonstrated that TPP 4 was present in the large, fast-sedimenting lysosomes (protein droplets) and in a heterogeneous broad band of smaller lysosomes. Equilibrium banding of the small lysosomes gave two distinct TPP 4-containing populations at densities 1.20 and 1.235 g/ml. Notably, dipeptidyl peptidase II (DPP II) gave identical banding densities and showed distributions very similar to TPP 4.(ABSTRACT TRUNCATED AT 250 WORDS)


Spontaneous Multiple Haematomas in a Patient with Severe COVID-19 Fully Recovered with a Conservative Approach.
A significant number of hospitalized patients with COVID-19 are prone to thromboembolic events including deep vein thrombosis, pulmonary embolism, cerebrovascular accident, and myocardial infarction. However, some COVID-19 patients have a higher risk of bleeding that is associated with an increased risk of mortality. We report a 71-year-old woman who was a confirmed case of COVID-19 admitted for pulmonary involvement and complicated acute renal failure. During hospitalization, she suffered from a sudden onset of severe pain in the lower left abdomen as well as a sudden drop in blood pressure and hemoglobin. Haematomas in the left rectus and obturator internus muscle were observed in abdominal and pelvic computed tomography scan. Signs of haemorrhage were also seen in the anterolateral aspect of the bladder with extension to the paracolic, subdiaphragmatic, perihepatic and, perisplenic spaces. The patient was totally recovered by a conservative approach. Bleeding tendency could be a serious complication, especially, in COVID-19 patients with complicated renal failure that receive heparin prophylaxis.


Rat liver L-threonine deaminase: properties and purification.
A new method of purification of rat liver L-threonine deaminase has been developed, and the results obtained are compared with values obtained by other authors. Some properties of this enzyme (pH optimum, temperature optimum, thermal stability, specificity, etc.) have been examined and we found that the enzyme is inhibited by carbonate ions, that L-cysteine (a competitive inhibitor) is also an inactivator of the enzyme and that it is bound to the enzyme in a ratio of 0.25 mole of cysteine per mole of enzyme, supporting the hypothesis that the enzyme consists of 4 subunits.


Cocaine abuse treatment: a review of current strategies.
The treatment of cocaine abusers is a newly emerging discipline. Many of the strategies that are being developed for this purpose have been adapted from the drug and alcoholism treatment systems. These include use of established programs that are only minimally modified for cocaine abusers, such as the 28-day inpatient hospital, therapeutic community, and 12-step programs. Other approaches have created specific techniques to meet particular clinical needs of cocaine abusers, such as behavioral, pharmacologic, and nontraditional interventions. Finally, several attempts have been made to create integrated outpatient approaches that address the multiple needs of the cocaine abusers. Many of the clinical researchers conducting research on these modalities feel optimistic about the value of treatment for cocaine abusers. Many of the methods appear to have considerable promise. However, only recently have well-controlled research efforts begun to provide the information necessary for empirically based decision-making. During the next several years, outcome studies should provide an excellent set of data to guide treatment efforts. This paper reviews the treatment efforts that have been conducted, overviews the research data available, and describes some of the outcome research in progress.


XMIPP: a new generation of an open-source image processing package for electron microscopy.
X-windows based microscopy image processing package (Xmipp) is a specialized suit of image processing programs, primarily aimed at obtaining the 3D reconstruction of biological specimens from large sets of projection images acquired by transmission electron microscopy. This public-domain software package was introduced to the electron microscopy field eight years ago, and since then it has changed drastically. New methodologies for the analysis of single-particle projection images have been added to classification, contrast transfer function correction, angular assignment, 3D reconstruction, reconstruction of crystals, etc. In addition, the package has been extended with functionalities for 2D crystal and electron tomography data. Furthermore, its current implementation in C++, with a highly modular design of well-documented data structures and functions, offers a convenient environment for the development of novel algorithms. In this paper, we present a general overview of a new generation of Xmipp that has been re-engineered to maximize flexibility and modularity, potentially facilitating its integration in future standardization efforts in the field. Moreover, by focusing on those developments that distinguish Xmipp from other packages available, we illustrate its added value to the electron microscopy community.


Effect of pain and analgesia on compensatory reserve.
The measurement of the body's capacity to compensate for reduced blood volume can be assessed with a compensatory reserve measurement (CRM). The CRM, which is calculated from changes in features of the arterial waveform, represents the integration of compensatory mechanisms during states of low tissue perfusion and oxygenation, such as hemorrhage. This study was designed to test the hypothesis that pain which activates compensatory mechanisms and analgesia that result in reduced blood pressure are associated with lower compensatory reserve. This study evaluated CRM in obstetric patients during labor as pain intensity increased from no pain to severe pain and compared CRM before and after epidural anesthesia. CRM was calculated from a finger pulse oximeter placed on the patient's index finger and connected to the DataOx monitor in healthy pregnant women (n = 20) before and during the active labor phase of childbirth. As pain intensity, based on an 11-point scale (0, no pain; 10, worst pain), increased from 0 to 8.4 ± 0.9 (mean ± SD), CRM was not affected (81 ± 10% to 82 ± 13%). Before analgesia, CRM was 84 ± 10%. CRM at 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, and 60 minutes after analgesia was 82 ± 11%, 83 ± 14%, 83 ± 15%, 86 ± 12%, 89 ± 9%, and 87 ± 10%, respectively. There was a transient 2% reduction followed by a 5% increase in CRM from before to after epidural anesthesia (p = 0.048). Pain scores before and after analgesia were 7 ± 2 and 1 ± 1, respectively (p < 0.001). These results indicate that pain and analgesia contribute minimally, but independently to the reduction in compensatory reserve associated with trauma and hemorrhage. As such, our findings suggest that analgesia can be safely administered on the battlefield while maintaining the maximal capacity of mechanisms to compensate for blood loss. Diagnostic study, level II.


The effects of partial and selective reduction in the components of the proton-motive force on lactose uptake in Escherichia coli.
The relationship between the steady state lactose accumulation (delta plac) and the magnitude of the membrane potential (delta psi) and pH gradient (delta pH) has been studied at pHo5.5 and pHo7.5. An attempt has been made to differentiate between two possible means by which lactose accumulation may be reduced below the proton-motive force (delta p). Firstly, that delta psi and delta pH are not equivalent in driving lactose transport and secondly, that 'slip' reactions (beta-galactoside exit via the carrier without a proton) may reduce accumulation. The data support the latter; however, our conclusions are tempered by the observation that the apparent stoichiometry (delta plac/delta p) increases to a value of at least 2 at values of delta p below 130 mV.


Different adjuvanticity of incomplete freund's adjuvant derived from beef or vegetable components in melanoma patients immunized with a peptide vaccine.
Adjuvants are requisite components of many vaccines designed to elicit T-cell immunity although the exact components of commonly used adjuvants are not always fully defined. In 2006, owing to concerns of prion contamination, the formulation of Montanide ISA 51 Incomplete Freund's Adjuvant (IFA) was changed from using oleic acid isolated from beef tallow to that isolated from olives. In sequential clinical trials in the Surgery Branch, NCI patients at high risk for recurrence of melanoma were immunized with the gp100 melanoma/melanocyte antigenic peptide, gp100: 209-217 (210M), emulsified in the beef-derived IFA or the olive-derived IFA. The in vivo generation of gp100 reactive T cells was significantly less in patients receiving the olive compared with the beef IFA as assessed by both ELISPOT (P2=0.0001) and in vitro sensitization assays (P2=0.0001). Local skin reactions to the peptide emulsion were also far less severe using the olive IFA (P2=0.0003). Thus it seems likely that contaminants in the beef-derived IFA played an important role in the increased adjuvanticity of this preparation compared with the olive-derived IFA. These findings raise serious concerns related to the use of the available olive-derived IFA for immunization in clinical trials. A survey of ongoing clinical trials listed in ClinicalTrials.gov revealed 36 trials currently accruing patients that are using the olive-derived Montanide ISA 51 IFA.