Role of 11C-choline PET/CT in radiation therapy planning of patients with prostate cancer.
In the era of image-guided radiotherapy, PET has become an important tool for tumor delineation in several types of cancer. The aim of this study was to evaluate the effect of this imaging modality in treatment planning of a cohort of patients with prostate cancer eligible for radiotherapy. From September 2011 to January 2016, 135 consecutive patients (median age 69 years, range: 53-89) were referred to our department for radiation therapy with radical intent (n=28), for postoperative adjuvant (n=13) or salvage treatment (n=50), for re-irradiation (n=19), or for radiotherapy on oligometastases (n=25). Before planning the radiotherapy course, patients were submitted to carbon-11-choline PET (Cho-PET) to confirm the indication to radiotherapy and the irradiation volumes. Among the 135 patients subjected to Cho-PET, the indication to radiotherapy was modified in 66 (48.8%) cases based on the Cho-PET result. In particular, Cho-PET helped to better define the radiotherapy programme in 12 out of 28 (42.8%) patients who were candidates for primary radiation therapy, 33 (52.4%) of 63 patients undergoing adjuvant/salvage radiotherapy, and 21 out of 44 (47.7%) patients with relapsed/metastatic disease. Overall biochemical response is documented by mean and median prostate specific antigen values, which changed from 15.29 to 4.00 ng/ml, respectively, before to mean 4.74 ng/ml and median 0.81 ng/ml after therapy (P=0.05). In our series, Cho-PET had a significant effect on radiotherapy planning of patients affected by prostate cancer, determining a change in management in 48.8% of cases, considering all therapeutic indications.


Eye and visual function in traumatic brain injury.
Combat blast is an important cause of traumatic brain injury (TBI) in the Department of Veterans Affairs polytrauma population, whereas common causes of TBI in the civilian sector include motor vehicle accidents and falls. Known visual consequences of civilian TBI include compromised visual acuity, visual fields, and oculomotor function. The visual consequences of TBI related to blast remain largely unknown. Blast injury may include open globe (eye) injury, which is usually detected and managed early in the rehabilitation journey. The incidence, locations, and types of ocular damage in eyes without open globe injury after exposure to powerful blast have not been systematically studied. Initial reports and preliminary data suggest that binocular function, visual fields, and other aspects of visual function may be impaired after blast-related TBI, despite relatively normal visual acuity. Damage to the ocular tissues may occur from blunt trauma without rupture or penetration (closed globe injury). Possible areas for research are development of common taxonomy and assessment tools across services, surgical management, and outcomes for blast-related eye injury; the incidence, locations, and natural history of closed globe injury; binocular and visual function impairment; quality of life in affected service members; pharmacological and visual therapies; and practice patterns for screening, management, and rehabilitation.


CCR5-∆32 is deleterious in the homozygous state in humans.
We use the genotyping and death register information of 409,693 individuals of British ancestry to investigate fitness effects of the CCR5-∆32 mutation. We estimate a 21% increase in the all-cause mortality rate in individuals who are homozygous for the ∆32 allele. A deleterious effect of the ∆32/∆32 mutation is also independently supported by a significant deviation from the Hardy-Weinberg equilibrium (HWE) due to a deficiency of ∆32/∆32 individuals at the time of recruitment.


Neurological complications during the Omicron COVID-19 wave in China: A cohort study.
The aim was to investigate the neurological complications associated with coronavirus disease 19 (COVID-19) during the 2022 Omicron wave. The medical records of a cohort of people admitted to neurological wards of three participating tertiary centres in Sichuan from 12 December 2022 to 12 January 2023 were reviewed. Demographics and clinical data were obtained and analysed with an interest in COVID-19-related new-onset or worse neurological symptoms. The current data were also compared in two centres with similar data from the same period 12 months earlier. In all, 790 people were enrolled, of whom 436 were positive for COVID-19. Ninety-nine had new onset COVID-related neurological problems, or their known neurological condition deteriorated during the wave. There was a significant difference in demographics from the findings amongst admissions 12 months earlier as there was an increase in the average age, the incidence of encephalitis and encephalopathy, and mortality rates. One hundred and one received COVID-specific antivirals, intravenous glucocorticoids and intravenous immunoglobulin therapy. No differences were seen between these and those who did not use them. New-onset neurological conditions, particularly encephalitis and encephalopathy, increased significantly during this period. Deterioration of existing neurological conditions, such as seizure exacerbation, was also observed. A large-scale treatment trial of people with COVID-19 infection presenting with neurological disorders is still needed.


Exploring the compassion deficit debate.
Several recent high profile failures in the UK health care system have promoted strong debate on compassion and care in nursing. A number of papers articulating a range of positions within this debate have been published in this journal over the past two and a half years. These articulate a diverse range of theoretical perspectives and have been drawn together here in an attempt to bring some coherence to the debate and provide an overview of the key arguments and positions taken by those involved. In doing this we invite the reader to consider their own position in relation to the issues raised and to consider the impact of this for their own practice. Finally the paper offers some sense of how individual practitioners might use their understanding of the debates to ensure delivery of good nursing care.


Factorial survival analysis for treatment effects under dependent censoring.
Factorial analyses offer a powerful nonparametric means to detect main or interaction effects among multiple treatments. For survival outcomes, for example, from clinical trials, such techniques can be adopted for comparing reasonable quantifications of treatment effects. The key difficulty to solve in survival analysis concerns the proper handling of censoring. So far, all existing factorial analyses for survival data have been developed under the independent censoring assumption, which is too strong for many applications. As a solution, the central aim of this article is to develop new methods for factorial survival analyses under quite general dependent censoring regimes. This will be accomplished by combining existing nonparametric methods for factorial survival analyses with techniques developed for survival copula models. As a result, we will present an appealing F-test that exhibits sound performance in our simulation study. The new methods are illustrated in a real data analysis. We implement the proposed method in an R function surv.factorial(.) in the R package compound.Cox.


[Complicated hydatid cysts of the liver].
In 328 cases of hydatid disease of the liver operated between 1979 and 1989, 51 (15.8%) had complicated cysts. The most frequent complication was intrabiliary rupture (2/3 of all complications). The others were intraperitoneal rupture in 7 cases (13.8%), suppuration in 7 cases (13.8%) and intrathoracic rupture in 3 cases (5.8%). Among the intrabiliary ruptured cysts, T-drainage was performed in 15 cases, choledochoduodenostomy was performed in 12 cases, and sphincteroplasty was performed in 7 cases. The cases of intraabdominal rupture were operated immediately. The suppurated cysts were marsupialized in 3 cases and drained in 4 cases. The 3 cases of bronchobiliary fistula were treated by T-tube drainage of the common bile duct, drainage of the pleural space, repair of the diaphragm and closure of the communicating bronchus. In this series, the mortality rate was 7.8% and the recurrence rate was 9.8%.


Association of macular thickness with parapapillary atrophy in myopic eyes.
To investigate whether macular structure could be affected by axial elongation and to determine the association between macular intraretinal thickness and the microstructure of β-zone parapapillary atrophy (PPA) in myopic eyes. The study recruited 113 healthy myopic subjects (113 eyes). Images of the macula, subfoveal choroid, and optic nerve head were acquired using spectral-domain optical coherence tomography (SD-OCT). An automatic segmentation algorithm was used to segment the macular images into 7 intraretinal layers. PPA widths with and without Bruch's membrane (PPA+BM and PPA-BM, respectively) were evaluated. Linear regression analysis was performed to evaluate the association between macular intraretinal thickness and axial length and the microstructure of PPA. An increase in axial length was associated with a decrease in whole macular thickness of the peripheral region and an increase in whole macular thickness of the central region. Thickness alterations of the macular intraretinal layers were most apparent in the peripheral region. A significant correlation was found between PPA-BM width and macular intraretinal layer thickness, whereas no significant correlation was found between PPA+BM width and macular intraretinal layer thickness. Moreover, both PPA+BM and PPA-BM widths significantly correlated with subfoveal choroidal thickness. Macular intraretinal layer thickness may be affected by PPA-BM width. These findings indicate that the microstructure of PPA should be considered when evaluating the macula in patient with myopia and glaucoma.


Concordance in Reported Love, Trust, and Relationship Quality among Same-Sex Male Relationships.
This paper examines concurrence of self-reported love, trust, and dyadic quality experiences between partners in 293 male couples. Significant yet poor concurrence was observed for all three self-reported relationship measures, but varied by relationship characteristics. Using an actor-partner interdependence model (APIM), actor and partner characteristics were shown to be associated with self-reported relationship concerns, such as satisfaction and intimate partner violence. This knowledge is important in the development and delivery of couples-based health interventions, such as couples HIV testing and counseling, for interventions that respect the unique relationship dynamics of each couple are needed to effectively address dyadic health.


Patterns of arthritis medication use in a community sample.
Although arthritis is disabling, highly prevalent, and often treated without health professional input, little is known about the treatments selected by affected individuals. Such information is important because of the toxicity associated with some arthritis treatments. To describe the pattern of drug treatment use in a sample of persons with arthritis. The authors distributed an 11-item survey to veterans attending veterans' organization post meetings in southeastern Wisconsin during November and December 2009. Of 32 posts, 26 (81%) returned surveys from 446 persons; survey count and attendance figures suggest that the majority of attendees completed surveys at participating posts. Most respondents were older (75% aged 60 years or older) men (90%). Respondents with arthritis reported whether they had used each of seven drug therapies in the past year. Almost all members of participating posts responded to the survey, increasing the likelihood that this was a representative sample. Most respondents (290 of 446, 65%) reported having arthritis, which impaired function in 78.6% of them. Most of those with arthritis (252 of 290, 86.9%) had used at least one drug treatment for arthritis in the last year. Acetaminophen use (41.0%) and use of an over-the-counter nonsteroidal anti-inflammatory drug (42.1%) were common. Nonsteroidal anti-inflammatory drug use did not decrease with older age or increase with greater functional impairment. Self-medication for arthritis is common and often does not follow clinical guidelines. Efforts to improve the quality of osteoarthritis care that focus solely on health care providers are unlikely to ensure optimal osteoarthritis care.


Comparison of the responses to hypoxia, ischaemia and ischaemic preconditioning in wild marmot and laboratory rabbit hearts.
Marmots (Marmota flaviventris) are burrowing mammals that may be subjected to low levels of oxygen and high levels of carbon dioxide in their underground environment. Since marmots successfully deal with this physiological challenge, we hypothesized that the isolated perfused marmot heart would be damaged less and recover better from a bout of induced hypoxia or ischaemia than would the heart of a comparison animal, the New Zealand laboratory rabbit (Oryctolagus cuniculus). Isolated marmot and rabbit hearts were made hypoxic by a 30 min perfusion with an oxygen-deficient buffer. The hearts were then perfused with an oxygen-replete buffer and measurements of heart rate, left ventricular pressure and lactate dehydrogenase (LDH) release (an indicator of cell damage) were made over 5 or 10 min intervals for 30 min of hypoxia and 30 min of recovery. There were no species differences in the responses, except that the heart rate in marmots was about 50% of the rate in rabbits during the hypoxia part of the experiment. There was no evidence that the marmot hearts were damaged less or recovered better from hypoxia and reoxgenation than the rabbit hearts. Marmot and rabbit hearts were also subjected to 30 min of total ischaemia; measurements of heart rate, left ventricular pressure and LDH release were obtained during 30 min of reperfusion and compared with the pre-ischaemia values for these variables. There were no significant species differences. When the 30 min ischaemic period was preceded by a 5 min period of ischaemia and a 10 min reperfusion period (preconditioning), the rabbit hearts were protected by this brief ischaemic insult and recovered better than the hearts that had not been subjected to the preconditioning ischaemia. This was not true in the marmot hearts, however, as the preconditioning ischaemia did not promote a greater recovery over that in its absence. When preconditioned marmots hearts were compared with preconditioned rabbit hearts, there were no statistical differences in the responses. The hypothesis that marmot hearts would be damaged less and recover better from hypoxia and ischaemia was not supported by the experimental data.


Rheological characteristics of tooth bleaching materials.
Tooth bleaching materials need to flow easily on insertion but should have high viscosity at low stresses to stay in place on the teeth. Some degree of elasticity may also aid retention on the teeth thereby maximizing efficacy. The present work was undertaken to study the comparative rheology of three tooth bleaching systems: two gels (Opalescence, Ultradent; Perfecta Trio, American Dental Hygienics) and a paste (Colgate Platinum, Colgate). A dynamic stress rheometer (Rheometrics Scientific) with cone and plate geometry was used, with the materials maintained at 37.0+/-0.1 degrees C with a vapour hood to minimize volatilization. Stress creep and recovery experiments were carried out. Steady shear viscosity for all three systems was high (>10(6) Pa s(-1)) for stresses <20 Pa. Between 100 and 200 Pa stress, all three materials showed a large drop in viscosity and flowed readily. The recovery portion of the data showed a marked difference where the elasticity of the gels was nearly two orders of magnitude higher than that of the paste. It was concluded that all materials would flow readily on insertion into the mouth and all have desirable high viscosity at low stress, but the paste material had the lowest elasticity. The effect of elasticity on performance needs to be determined clinically.


The Relationship Between Physical Characteristics and Maximal Strength in Men Practicing the Back Squat, the Bench Press and the Deadlift.
This study was designed to quantify the relationships between physical characteristics and maximal strength in the back squat, the bench press and the deadlift on powerlifters and football players. Eighteen male junior drug-tested classic powerlifters and seventeen NCAA Division II American football players' anthropometric measurements were taken to compare them with maximal strength results from either a powerlifting meet or testing from their supervised strength and conditioning program. Pearson's bivariate correlations analysis revealed (statistical significance was set at p<0.05) that individuals with a greater (Wilks points) back squat, generally presented a higher Bodyweight (BW) (r=0.37), Body Mass Index (BMI) (r=0.45), Bodyfat Percentage (BF%) (r=0.36), Hip (r=0.41), Waist (r=0.35) and Torso (r=0.41) Circumference (C), Hip C/Height (r=0.46), Waist C/Height (r=0.39) and Torso C/Height (r=0.45) ratios. The individuals with a greater bench press generally presented a higher BMI (r=0.37), Lean Body Weight (LBW) (r=0.36), Hip C (r=0.39) and Hip C/Height ratio (r=0.39). On the other hand, individuals with a greater deadlift were generally older (r=0.34), shorter (r=-0.41), had shorter thighs (r=-0.52) and trunks (r=-0.36), smaller Thigh Length (L)/Height ratio (r=-0.44), Waist C/Hip C (r=-0.41) and Thigh L/Lower Leg L (r=-0.53) ratios, but a higher Lower Leg L/Height ratio (r=-046). The results of this study should be utilized by strength and conditioning coaches to deepen their comprehension of their athletes' physical characteristics in order to help them develop strength through their advantages. Further research should focus on evaluating how physical characteristics affect performance in different squat, bench, and deadlift stances.


Variola minor in coalfield areas of England and Wales, 1921-34: Geographical determinants of a national smallpox epidemic that spread out of effective control.
This paper uses techniques of binary logistic regression to identify the spatial determinants of the last national epidemic of smallpox to spread in England and Wales, the variola minor epidemic of 1921-34. Adjusting for age and county-level variations in vaccination coverage in infancy, the analysis identifies a dose-response gradient with increasing odds of elevated smallpox rates in local government areas with (i) medium (odds ratio [OR] = 5.32, 95% Confidence Interval [95% CI] 1.96-14.41) and high (OR = 11.32, 95% CI 4.20-31.59) coal mining occupation rates and (ii) medium (OR = 16.74, 95% CI 2.24-125.21) and high (OR = 63.43, 95% CI 7.82-497.21) levels of residential density. The results imply that the spatial transmission of variola virus was facilitated by the close spatial packing of individuals, with a heightened transmission risk in coal mining areas of the country. A syndemic interaction between common respiratory conditions arising from exposure to coal dust and smallpox virus transmission is postulated to have contributed to the findings. We suggest that further studies of the geographical intersection of coal mining and acute infections that are transmitted via respiratory secretions are warranted.


Long-term outcome after prophylactic lamivudine treatment on hepatitis B virus reactivation in non-Hodgkin's lymphoma.
Hepatitis B virus (HBV) reactivation is the frequent complication after cytotoxic chemotherapy in HBsAg-positive non-Hodgkin's lymphoma (NHL) patients. Pre-chemotherapy viral load may be a risk factor and HBeAg-positive status is associated with increased viral load. The aim of this study was to investigate the long-term treatment outcome of lamivudine in preventing HBV reactivation and its associated morbidity according to HBeAg status. Twenty-four adult HBsAg-positive NHL patients were taken 100 mg of lamivudine daily before the initiation of chemotherapy. The median duration of lamivudine therapy was 11.5 months (range: 1-54 months) and the median number of chemotherapy cycles was 6 (range: 1-16 cycles). The steroid containing chemotherapy regimens were used in 18 patients (75%), and the anti-CD20 monoclonal antibody containing chemotherapy regimen was used in 6 patients (25%). Four patients received autologous peripheral blood stem cell transplantation without resultant HBV reactivation. Hepatitis related to HBV reactivation was developed in 1 patient among 14 HBeAg-positive patients and no one among 10 HBeAg-negative. One patient developed HBV reactivation after lamivudine withdrawal, and 4 patients developed the YMDD (tyrosine-methionine-aspartate-aspartate) mutation during lamivudine therapy. There were no statistical differences in HBV reactivation rate during chemotherapy according to the HBeAg status. Our results demonstrate that lamivudine should be considered preemptively before the chemotherapy for all HBsAg-positive NHL patients to prevent HBV reactivation, regardless of pre-chemotherapy HBeAg status. Finally, compared with the chronic hepatitis B patients, similar rate of HBV reactivation after lamivudine withdrawal and development of YMDD mutation was observed in NHL patients.


[Mediastinal fibrosis combined with Behçet's disease. Three case reports].
Intrathoracic manifestations other then vascular aneurysm and thrombosis are rare in the course of Behçet's disease. Mediastinal fibrosis is also unusual. Three cases of Behçet's disease with initial mediastinal fibrosis are reported. Diagnosis means, pathogenic mechanisms and therapeutic modalities are also more precisely defined. Three male patients (21, 25 and 27 years of age, respectively) were hospitalized for progressive vena cava superior syndrome accompanied by mediastinal fibrosis demonstrated by MRI and/or CT scan which both showed infiltration of the mediastinal fat. Multiple calcifications were also present in one patient. Histology was performed in one case. Thrombosis of the vena cava superior and innominata veins was associated with fibrosis in all three cases. Thrombosis of venae subclavia and left jugularis was also present in one case. Other manifestations leading to the diagnosis of Behçet's disease were demonstrated by the patient's history and, in one case, occurred on the fourth day of hospitalization. After initiation of a treatment including corticoids, anticoagulants and colchicine, the outcome was favorable in two cases. The third patient died. Mediastinal fibrosis combined with Behçet's disease has rarely been described. However, it should be included in manifestations of the disease. The causative process which might be vasculitis has to be demonstrated.


[The inner coherence of psychosomatic medicine].
The body-mind dualism of somatic medicine is resolved through the concept of psychosomatic medicine. More unspecific descriptions such as "integrative medicine" (which does not clarify what should be integrated) or the "holistic approach" (which comes close to esoterics) suggest the unity of mind, body and soul, although the term "psycho-somatic" still reflects dualistic thinking. The American Psychosomatic Society has been considering a name change for years, partially to rid itself of the dualistic label, but so far these efforts have not resulted in a viable alternative. Engel's concept of biopsychosocial medicine supposes a triangular array of the body, mind, and social environment, setting body and mind into a relationship with each other and with a third party. Based on the physician-patient relationship (Balint), psychosomatic medicine can be understood in a broader sense as "relationship medicine," covering not only the use of the interpersonal relationship as a medical agent, but also a science of medicine that puts mind, body, and social environment into a theoretical framework of interrelations, with the perspective of integrating the different system levels. The translation processes among the system levels are, for example, addressed by biosemiotics (v. Uexküll). Both clinical medicine and medical research, if they intend to be psychosomatic, need to take these theoretical concepts into account and utilize them practically for (team)work with patients. Together with a clear differentiation from other cultures of (para)medicine, this can serve to develop a "psychosomatic identity."


Citizen Science on Your Smartphone: An ELSI Research Agenda.
The prospect of newly-emerging, technology-enabled, unregulated citizen science health research poses a substantial challenge for traditional research ethics. Unquestionably, a significant amount of research ethics study is needed to prepare for the inevitable, widespread introduction of citizen science health research. Using the case study of mobile health (mHealth) research, this article provides an ethical, legal, and social implications (ELSI) research agenda for citizen science health research conducted outside conventional research institutions. The issues for detailed analysis include the role of IRBs, recruitment, inclusion and exclusion criteria, informed consent, confidentiality and security, vulnerable participants, incidental findings, and publication and data sharing.


Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk.
Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.


Estimating community drug abuse by wastewater analysis.
The social and medical problems of drug abuse are a matter of increasing global concern. To tackle drug abuse in changing scenarios, international drug agencies need fresh methods to monitor trends and patterns of illicit drug consumption. We tested a sewage epidemiology approach, using levels of excreted drug residues in wastewater, to monitor collective use of the major drugs of abuse in near real time. Selected drug target residues derived from use of cocaine, opiates, cannabis, and amphetamines were measured by mass spectrometry in wastewater collected at major sewage treatment plants in Milan (Italy), Lugano (Switzerland), and London (United Kingdom). The amounts of drug residues conveyed to the treatment plants, reflecting the amounts collectively excreted with urine, were used to estimate consumption of the active parent drugs. Reproducible and characteristic profiles of illicit drug use were obtained in the three cities, thus for the first time quickly revealing changes in local consumption (e.g., cocaine consumption rose significantly on weekends in Milan). Profiles of local drug consumption based on waste-water measurements are in line with national annual prevalence estimates. Patterns and trends of drug abuse in local communities can be promptly monitored by this tool, a convenient new complement to more complex, lengthy survey methods. In principle, searching the sewage for excreted compounds relevant to public health issues appears to have the potential to become a convenient source of real-time epidemiologic information.


Examination of parental knowledge of child weight status and associated potential health risks.
The identification of parental health knowledge related to obesity and overweight status in children is an important area. Its importance relates to understanding gaps in knowledge that can be used to create targeted intervention and prevention strategies to improve the management of child's weight. There is a growing awareness of the potential health risks associated with increased childhood weight. It is currently unclear how well the public understands these risks and if understanding is linked to improvement in obesity or overweight levels in children. This review focused on determining if the current research is available to describe parental knowledge and whether it is connected to improved outcomes in the child's weight status. The search for original research articles published between 2003 and 2018 involved six databases, including CINAHL, EBSCOhost, PubMed, PsycINFO, Psychology, and Behavioral Sciences Collection, and OneSearch. The OneSearch database is a comprehensive search engine that allows simultaneous searching of the entire library category and results that are ranked by relevance to the search terms. The terms used included for the keyword search in each database included: "knowledge" or "awareness," "health risk" or "consequence," "obesity" or "overweight," and "weight" or "body mass index," "child," and "parent" or "parental." A content analysis of included articles was performed to synthesize available literature into a review. This review included nine articles dealing specifically with parents of children and their knowledge levels. As there was limited information about if child's weight status connected to parental knowledge, an additional seven articles addressing how knowledge affects weight at any age was examined. The findings for parental knowledge and its effect have mixed results and varying methods of measurement. While some studies have indicated the importance of knowledge, it is difficult to establish a reliable connection due to the limited examination of this subject. This is, therefore, an underexplored area that needs further study.


Enhanced cellular radiosensitivity induced by cofilin-1 over-expression is associated with reduced DNA repair capacity.
A previous report has indicated that over-expression of cofilin-1 (CFL-1), a member of the actin depolymerizing factor (ADF)/cofilin protein family, enhances cellular radiosensitivity. This study explores the involvement of various DNA damage responses and repair systems in the enhanced cellular radiosensitivity as well as assessing the role of CFL-1 phosphorylation in radiosensitivity. Human non-small lung cancer H1299 cells harboring a tet-on gene expression system were used to induce exogenous expression of wild-type CFL-1. Colony formation assays were used to determine cell survival after γ-ray exposure. DNA damage levels were determined by Comet assay. DNA repair capacity was assessed by fluorescence-based DNA repair analysis and antibody detection of various repair proteins. The effects of CFL-1 phosphorylation on radiation responses were explored using two mutant CFL-1 proteins, S3D and S3A. Finally, endogenous CFL-1 phosphorylation levels were investigated using latrunculin A (LA), cytochalasin B (CB) and Y27632. When phosphorylatable CFL-1 was expressed, radiosensitivity was enhanced after exposure to γ-rays and this was accompanied by DNA damage. Phosphorylated histone H2AX (γ-H2AX) and p53-binding protein-1 (53BP1) foci, as well as Chk1/2 phosphorylation, were apparently suppressed, although ataxia telangiectasia mutated (ATM) kinase activation was apparently unaffected. In addition, two radiation-induced double-strand break (DSB) repair systems, namely homologous recombination repair (HRR) and non-homologous end joining (NHEJ), were suppressed. Moreover, over-expression of CFL-1 S3D and CFL-1 S3A both enhanced radiosensitivity. However, enhanced radiosensitivity and reduced γ-H2AX expression were only detected in cells treated with LA which increased endogenous phospho-CFL-1, and not in cells treated with Y27632, which dephosphorylates CFL-1. CFL-1 over-expression enhances radiosensitivity and this is associated with reduced DNA repair capacity. Although phosphorylated CFL-1 seems to be involved in radiosensitivity, further studies are required to address the importance of CFL-1 activity to the regulation of radiosensitivity.


Cystatin C in paediatric nephrology. Present situation and prospects.
Cystatin C is a small basic protein with a MW of 13,359 Daltons, consisting of a non-glycosylated polypeptide chain containing 120 amino-acid residues. Cystatin C is produced in all the nucleated cells of the human body and its output rate is constant. The kidney is the main catabolic site of cystatin C, since the protein, by virtue of its low MW and its positive charge at normal pH, is freely filtered by the glomerulus and almost completely reabsorbed, catabolised and broken down in the cells of the proximal convoluted tubule. It is practically entirely filtered via the glomerular membrane, without any significant tubular secretion. The constant production rate of cystatin C in all the tissues, its elimination via the glomerular filter and its non-dependence on many extrinsic factors, including sex, age, diet, inflammation, are potentially ideal conditions for an endogenous biochemical marker of glomerular filtration. A recent method for determining cystatin C, is based on an immune reaction, could increase its clinical application. Not many studies have been conducted to date on cystatin C in children. The cystatin C concentration was higher during the first few days of life (range: 1.64-2.59 mg/L) with a rapid reduction during the first 4 months. Beyond the first year of life, cystatin C concentration became constant, with a reference range of 0.7-1.38 mg/L. On the basis of the data currently available, neonatal serum cystatin C would appear to derive from the newborn itself. In fact no correlations were found between maternal and neonatal serum cystatin C values. Cystatin C determination appears to be at least equivalent to serum creatinine measurement for the assessment of glomerular filtration rate in children. Further extended studies are needed to investigate these aspects more thoroughly in neonates.


The novel genetic disorder microhydranencephaly maps to chromosome 16p13.3-12.1.
We studied a large consanguineous Anatolian family with children who exhibited hydranencephaly associated with microcephaly. The children were severely affected. This novel genetic disorder is autosomal recessive. We used autozygosity mapping to identify a locus at chromosome 16p13.3-12.1; it has a LOD score of 4.11. The gene locus is within a maximal 11-cM interval between markers D16S497 and D16S672 and within a minimal critical region of 8 cM between markers D16S748 and D16S490.


Decreased UV absorbance as an indicator of micropollutant removal efficiency in wastewater treated with ozone.
Ozone transforms various organic compounds that absorb light within the UV and visible spectra. UV absorbance can therefore be used to detect the transformation of chemicals during ozonation. In wastewater, decolourisation can be observed after ozonation. This study investigates the correlation of the UV absorbance difference between the ozonation inlet and outlet and the removal efficiency of micropollutants in wastewater. The absorbance at 254 and 366 nm was measured at the ozonation inlet and outlet, as was the concentration of 24 representative micropollutants and the dissolved organic carbon (DOC). The results clearly showed that the relative decrease of absorbance (ΔAbs) is positively correlated with the relative removal efficiency of micropollutants. We therefore suggest that UV absorbance can be used as a feedback control parameter to achieve optimal ozone dosage in wastewater treatment plants and to gain a fast insight into the process efficiency and stability of the ozonation.


Monoclonal antibodies recognizing single amino acid substitutions in hemoglobin.
Four monoclonal antibodies (mAb) to non-human primate hemoglobin referred to as Cap-4, Cap-5, Rh-2, and Rh-4, and two mAb to human hemoglobin, referred to as H-1 and H-3 were isolated and were partially characterized. Binding studies with these mAb on a panel of hemoglobins and isolated alpha and beta globin chains revealed a unique reactivity pattern for each mAb. Amino acid sequence analysis of the antigens used to generate the binding data suggests that the specific recognition of certain hemoglobin antigens by each mAb is controlled by the presence of a particular amino acid at a specific position within the epitope. The use of synthetic peptides as antigens confirmed this observation for five of the mAb. No synthetic peptides were tested with the sixth mAb, Rh-2. The amino acids required for binding of mAb Cap-4, Cap-5, Rh-4, and Rh-2 to hemoglobin are alanine at beta 5, threonine at beta 13, glutamine at beta 125, and leucine at alpha 68. The non-human primate hemoglobin antibodies require a specific amino acid that is not present in human hemoglobin. The amino acid required for binding of Cap-4, Cap-5, and Rh-4 could arise by a single base change in the beta globin gene, whereas the amino acid required for Rh-2 binding would only occur if two base changes occurred. Thus these mAb are candidate probes for a somatic cell mutation assay on the basis of the detection of peripheral blood red cells that possess single amino acid substituted hemoglobin as a result of single base substitutions in the globin genes of precursor cells.


A simpler approach to seal severe coronary perforation with bare metal stent.
The case of a coronary artery perforation in which overinflation of a balloon at an angulated segment of the left anterior descending (LAD) artery after stent deployment resulted in an Ellis type III coronary artery perforation is presented. A bare metal stent (BMS) was used successfully to seal this high-grade perforation. Here, it is demonstrated that it may not be illogical to consider BMS as the first choice before embarking on use of a covered stent if the clinical/haemodynamic condition of the patient allows it and if a covered stent is not available.


Safety and immunogenicity of boosting BCG vaccinated subjects with BCG: comparison with boosting with a new TB vaccine, MVA85A.
To investigate the safety and immunogenicity of a booster BCG vaccination delivered intradermally in healthy, BCG vaccinated subjects and to compare with a previous clinical trial where BCG vaccinated subjects were boosted with a new TB vaccine, MVA85A. Phase I open label observational trial, in the UK. Healthy, HIV-negative, BCG vaccinated adults were recruited and vaccinated with BCG. The primary outcome was safety; the secondary outcome was cellular immune responses to antigen 85, overlapping peptides of antigen 85A and tuberculin purified protein derivative (PPD) detected by ex vivo interferon-gamma (IFN-gamma) ELISpot assay and flow cytometry. BCG revaccination (BCG-BCG) was well tolerated, and boosting of pre-existing PPD-specific T cell responses was observed. However, when these results were compared with data from a previous clinical trial, where BCG was boosted with MVA85A (BCG-MVA85A), MVA85A induced significantly higher levels (>2-fold) of antigen 85-specific CD4+ T cells (both antigen and peptide pool responses) than boosting with BCG, up to 52 weeks post-vaccination (p = 0.009). To identify antigen 85A-specific CD8+ T cells that were not detectable by ex vivo ELISpot and flow cytometry, dendritic cells (DC) were used to amplify CD8+ T cells from PBMC samples. We observed low, but detectable levels of antigen 85A-specific CD8+ T cells producing IFNgamma (1.5% of total CD8 population) in the BCG primed subjects after BCG boosting in 1 (20%) of 5 subjects. In contrast, in BCG-MVA85A vaccinated subjects, high levels of antigen 85A-specific CD8+ T cells (up to 14% total CD8 population) were observed after boosting with MVA85A, in 4 (50%) of 8 subjects evaluated. In conclusion, revaccination with BCG resulted in modest boosting of pre-existing immune responses to PPD and antigen 85, but vaccination with BCG-MVA85A induced a significantly higher response to antigen 85 and generated a higher frequency of antigen 85A-specific CD8+ T cells. ClinicalTrials.gov NCT00654316 NCT00427830.


Optimization Growth of Spirulina (Arthrospira) Platensis in Photobioreactor Under Varied Nitrogen Concentration for Maximized Biomass, Carotenoids and Lipid Contents.
Spirulina (Arthrospira) platensis (SP) microalgae were cultured in Zarrouk Medium (ZM), containing three nitrogen concentrations (N-limited, N-optimal and Nrich medium) in ten liter-photo-bioreactor (10 L PBR) for 15-days, in order to study changes in lipid compounds (total carotenoids and total lipids and their effect on fatty acid profile). Based on US patent, the yield of bioactive compounds (such as gamma-linolenic acid GLA, C18:3) extracted from microalgae biomass, mainly depends on the extraction processes (1). GLA has much attention with respect to its therapeutic properties such as its ability to decrease blood cholesterol levels. The impact of the addition of N in cultures of S. platensis in terms of growth, biomasses and induced lipid compounds (total carotenoids and total lipid contents and its fatty acid profile), as well as the Sonication (SON) and Microwave (MIC) process as aiding techniques for lipid extraction compared with a Cold Condition (COL), was examined. GC/MS method was used to determine the fatty acid profile of lipid extract of SP cultures. In all S. platensis tested culture, the SP was growing successfully, with varying degrees. In N-rich media, the highest cell growth rate and biomass yield were obtained compared with that recorded in other cultures. Under an N-limited condition, SP had higher Total Carotenoids (TCAR, 45.54 mg/g dw) and total lipid contents (TL, 29.51%± 1.92 g/100g dw) compared with that recorded either in N-rich (11.2 mg/g dw) or in N-optimal (6.23 mg/g dw) cultures. Thus, SP copes with the N -stress by altering the metabolic pathways towards inducing lipid biosynthesis. To maximize the TL and TCAR extraction yields, from N-limited cultures, a set of operating process was applied including the Sonication (SON) and Microwave (MIC), which were used as aiding techniques for lipid extraction compared with the Cold Condition (COL) techniques. The results showed that the extraction efficiency of the S. platensis TL increased in the following order: MIC (29.51%± 1.92) > SON (25.46% ± 1.65> COL (20.43% ±1.43). In a comparative study for its fatty acid profiles (FAPs) among all SP cultures, lipids were analyzed by GC/MS. The predominant fatty acids (>10%, of total FA) were found to be myristic acid (C14:0, MA), palmitic acid (C16:0, PA) and oleic acid (C18:1). The study concluded that the N-limited condition was found to have a strong influence on biomass dry weight and lipid contents and total carotenoids in SP cells compared to either Nrich or N-optimal conditions. The use of sonication and the microwave techniques lead to a great increase in the extraction of lipid contents and in high amount Polyunsaturated Fatty Acids (PUFAs) in N-limited cultures, in particular, the omega-6 (ω 6) and omega-3 (ω 3) of the essential C18 fatty acids. It seems that the SP rich in lipid content with a high amount of GLC produced under nitrogen limitation in PBR conditions can be used as a food additive or as a nutritional supplement.


Vascularized double-sided preputial island flap with W flap glanuloplasty for hypospadias repair.
Hypospadias surgery is one of the most challenging surgical interventions that still need further refinements for increased success rates. During the last 5 years, we operated on 26 mid-penile or proximal hypospadias cases by using vascularized double-sided preputial island flap and W flap glanuloplasty to achieve superior functional and aesthetic results. Follow-up period of the patients revealed a 92.3 percent success rate with a single operation. Two cases developed fistula, which was located at the proximal anastomosis site. However, they were repaired in a second sitting without any additional problem. The basic aim in hypospadias surgery is the correction of chordee, reconstruction of urethra, and sufficient ventral penile skin coverage in one stage with minimal complication. The use of vascularized tissue for urethral reconstruction and ventral coverage is believed to have a superior healing capacity with better functional and cosmetic outcome. On the other hand, adding W flap glanuloplasty to this technique avoids the risk of meatal stenosis. We conclude that by combining the two above-mentioned techniques, it is possible to cope better with this devastating congenital deformity.


Bacteria of an anaerobic 1,2-dichloropropane-dechlorinating mixed culture are phylogenetically related to those of other anaerobic dechlorinating consortia.
A 16S-rDNA-based molecular study was performed to determine the bacterial diversity of an anaerobic, 1,2-dichloropropane-dechlorinating bioreactor consortium derived from sediment of the River Saale, Germany. Total community DNA was extracted and bacterial 16S rRNA genes were subsequently amplified using conserved primers. A clone library was constructed and analysed by sequencing the 16S rDNA inserts of randomly chosen clones followed by dot blot hybridization with labelled polynucleotide probes. The phylogenetic analysis revealed significant sequence similarities of several as yet uncultured bacterial species in the bioreactor to those found in other reductively dechlorinating freshwater consortia. In contrast, no close relationship was obtained with as yet uncultured bacteria found in reductively dechlorinating consortia derived from marine habitats. One rDNA clone showed >97% sequence similarity to Dehalobacter species, known for reductive dechlorination of tri- and tetrachloroethene. These results suggest that reductive dechlorination in microbial freshwater habitats depends upon a specific bacterial community structure.


Novel anti-obesity peptide (RLLPH) derived from hazelnut (Corylus heterophylla Fisch) protein hydrolysates inhibits adipogenesis in 3T3-L1 adipocytes by regulating adipogenic transcription factors and adenosine monophosphate-activated protein kinase (AMPK) activation.
Hazelnut proteins are an excellent source of bioactive peptides. Our previous study demonstrated that several novel peptides derived from Corylus heterophylla Fisch (C. heterophylla Fisch) have antioxidant and anti-inflammatory activities. In this study, we purified and identified anti-obesity peptides from hazelnut protein hydrolysates by chromatography and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Subsequently, we evaluated the inhibitory effect of the synthetic peptide on adipogenesis in 3T3-L1 adipocytes by Oil Red O staining, reverse transcription polymerase chain reaction (RT-PCR) and western blot. The results showed that a novel synthetic pentapeptide, Arg-Leu-Leu-Pro-His (RLLPH), derived from the C3 fraction, attenuated adipogenesis by downregulating the expression of several mRNAs related to adipogenesis, including peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding protein alpha (C/EBPα), adipocyte fatty acid-binding protein 2 (aP2), sterol regulatory element binding protein 1c (SREBP-1c), fatty acid synthase (FAS), acetyl-CoA carboxylase 1 (ACC1), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Moreover, RLLPH upregulated the levels of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and its substrate acetyl-CoA carboxylase (ACC) in 3T3-L1 adipocytes. A stability study revealed that RLLPH was relatively stable during pepsin digestion. These findings suggest that RLLPH has potential anti-obesity effects and may help combat metabolic diseases.


Direct and rapid genotyping of SLCO1B1 388A>G and 521T>C in human blood specimens using the SmartAmp-2 method.
Organic anion-transporting polypeptide (OATP) 1B1, encoded by the solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene, mediates the active uptake of various organic anions into hepatocytes and determines their hepatic clearances as the first step in the detoxification pathway. Previous reports indicated that alterations in its function by drug-drug interactions or genetic polymorphisms affect the pharmacokinetics of the substrate drugs. In the present study, we developed a method to genotype SLCO1B1 388A>G (rs2306283) and 521>C (rs4149056), which significantly affect the clinical pharmacokinetics and subsequent side effects such as myopathy caused by statins, OATP1B1 substrates in humans. We used a small aliquot of blood and the isothermal Smart Amplification Process version 2 (SmartAmp-2), which could complete the genotyping of 388A>G and 521T>C within 60 min. The genotypes of 101 genomic DNA samples and blood samples assessed by SmartAmp-2 matched perfectly to those determined previously by the conventional PCR-SSCP method. The SmartAmp-2 method enables the rapid identification of the 388A>G and 521T>C genotypes, saving time and effort in the genomic DNA preparation in clinical practice. This method will be useful for evaluating and predicting altered pharmacological and toxicological effects of substrate drugs caused by SLCO1B1 polymorphisms.


Ainhum--a case report.
AINHUM which has been described as one of the conditions to be differentiated from leprosy was met in the field in a village of Andhra Pradesh. The condition was found in a young adult male involving both the little toes. It was found to be slow progressive associated with pain.


Abscisic acid induces ectopic outgrowth in epidermal cells through cortical microtubule reorganization in Arabidopsis thaliana.
Abscisic acid (ABA) regulates seed maturation, germination and various stress responses in plants. The roles of ABA in cellular growth and morphogenesis, however, remain to be explored. Here, we report that ABA induces the ectopic outgrowth of epidermal cells in Arabidopsis thaliana. Seedlings of A. thaliana germinated and grown in the presence of ABA developed ectopic protrusions in the epidermal cells of hypocotyls, petioles and cotyledons. One protrusion was formed in the middle of each epidermal cell. In the hypocotyl epidermis, two types of cell files are arranged alternately into non-stoma cell files and stoma cell files, ectopic protrusions being restricted to the non-stoma cell files. This suggests the presence of a difference in the degree of sensitivity to ABA or in the capacity of cells to form protrusions between the two cell files. The ectopic outgrowth was suppressed in ABA insensitive mutants, whereas it was enhanced in ABA hypersensitive mutants. Interestingly, ABA-induced ectopic outgrowth was also suppressed in mutants in which microtubule organization was compromised. Furthermore, cortical microtubules were disorganized and depolymerized by the ABA treatment. These results suggest that ABA signaling induces ectopic outgrowth in epidermal cells through microtubule reorganization.


Insulin-receptor cDNA sequence in NIDDM patient homozygous for insulin-receptor gene RFLP.
Resistance to insulin action is a well-established feature of non-insulin-dependent diabetes mellitus (NIDDM) and is believed to contribute to the etiology of this condition. A strong genetic contribution to the etiology of NIDDM exists, and we previously identified an insulin-receptor gene restriction-fragment-length polymorphism (RFLP) associated with the NIDDM phenotype. In an attempt to elucidate whether structural defects in the insulin receptor could be a primary cause of insulin resistance in NIDDM, we analyzed the insulin-receptor cDNA sequence in a subject with NIDDM who is also homozygous for this RFLP. The insulin-receptor cDNA was sequenced with the polymerase chain reaction (PCR). mRNA from transformed lymphocytes was reverse transcribed and amplified with five overlapping sets of primers that span the coding sequence of both alpha- and beta-subunits. No difference was found in the predicted amino acid sequence of the subject's insulin receptor compared with the normal insulin receptor. At nucleotide positions 831 and 2247, the subject is heterozygous for silent nucleotide polymorphisms that do not affect the amino acid sequence. Exon 11 encodes a 12-amino acid insert in the alpha-subunit, which, due to alternate splicing, is not expressed in lymphocyte insulin-receptor mRNA. Consequently, exon 11 was amplified from genomic DNA by PCR; the sequence of exon 11 was found to be normal. In addition, when this patient's transformed lymphocytes were maintained in culture, no abnormalities in insulin binding were observed. We conclude that the insulin resistance seen in this NIDDM subject is not due to a structural alteration in the insulin receptor itself.(ABSTRACT TRUNCATED AT 250 WORDS)


Exercise and arthritis. Adaptive bicycling.
Bicycling, both indoor and outdoor, seems to be an excellent exercise for most patients with arthritis because it meets the criteria for the ideal recreational physical activity. This article outlines the physical and biomechanical advantages of bicycling as exercise and familiarizes the reader with the types of equipment available for both outdoor and indoor use. The proper mechanics of efficient bicycling and appropriate fit of machine to rider are addressed. Finally, guidelines are offered to initiate both indoor and outdoor cycling programs.


An experimental paradigm for the prediction of Post-Operative Pain (PPOP).
Many women undergo cesarean delivery without problems, however some experience significant pain after cesarean section. Pain is associated with negative short-term and long-term effects on the mother. Prior to women undergoing surgery, can we predict who is at risk for developing significant postoperative pain and potentially prevent or minimize its negative consequences? These are the fundamental questions that a team from the University of Washington, Stanford University, the Catholic University in Brussels, Belgium, Santa Joana Women's Hospital in São Paulo, Brazil, and Rambam Medical Center in Israel is currently evaluating in an international research collaboration. The ultimate goal of this project is to provide optimal pain relief during and after cesarean section by offering individualized anesthetic care to women who appear to be more 'susceptible' to pain after surgery. A significant number of women experience moderate or severe acute post-partum pain after vaginal and cesarean deliveries. (1) Furthermore, 10-15% of women suffer chronic persistent pain after cesarean section. (2) With constant increase in cesarean rates in the US (3) and the already high rate in Brazil, this is bound to create a significant public health problem. When questioning women's fears and expectations from cesarean section, pain during and after it is their greatest concern. (4) Individual variability in severity of pain after vaginal or operative delivery is influenced by multiple factors including sensitivity to pain, psychological factors, age, and genetics. The unique birth experience leads to unpredictable requirements for analgesics, from 'none at all' to 'very high' doses of pain medication. Pain after cesarean section is an excellent model to study post-operative pain because it is performed on otherwise young and healthy women. Therefore, it is recommended to attenuate the pain during the acute phase because this may lead to chronic pain disorders. The impact of developing persistent pain is immense, since it may impair not only the ability of women to care for their child in the immediate postpartum period, but also their own well being for a long period of time. In a series of projects, an international research network is currently investigating the effect of pregnancy on pain modulation and ways to predict who will suffer acute severe pain and potentially chronic pain, by using simple pain tests and questionnaires in combination with genetic analysis. A relatively recent approach to investigate pain modulation is via the psychophysical measure of Diffuse Noxious Inhibitory Control (DNIC). This pain-modulating process is the neurophysiological basis for the well-known phenomenon of 'pain inhibits pain' from remote areas of the body. The DNIC paradigm has evolved recently into a clinical tool and simple test and has been shown to be a predictor of post-operative pain.(5) Since pregnancy is associated with decreased pain sensitivity and/or enhanced processes of pain modulation, using tests that investigate pain modulation should provide a better understanding of the pathways involved with pregnancy-induced analgesia and may help predict pain outcomes during labor and delivery. For those women delivering by cesarean section, a DNIC test performed prior to surgery along with psychosocial questionnaires and genetic tests should enable one to identify women prone to suffer severe post-cesarean pain and persistent pain. These clinical tests should allow anesthesiologists to offer not only personalized medicine to women with the promise to improve well-being and satisfaction, but also a reduction in the overall cost of perioperative and long term care due to pain and suffering. On a larger scale, these tests that explore pain modulation may become bedside screening tests to predict the development of pain disorders following surgery.


Guidelines for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 8: lumbar fusion for disc herniation and radiculopathy.
There is no convincing medical evidence to support the routine use of lumbar fusion at the time of a primary lumbar disc excision. There is conflicting Class III medical evidence regarding the potential benefit of the addition of fusion in this circumstance. Therefore, the definite increase in cost and complications associated with the use of fusion are not justified. Patients with preoperative lumbar instability may benefit from fusion at the time of lumbar discectomy; however, the incidence of such instability appears to be very low (< 5%) in the general lumbar disc herniation population. Patients who suffer from chronic low-back pain, or are heavy laborers or athletes with axial low-back pain, in addition to radicular symptoms may also be candidates for fusion at the time of lumbar disc excision. Patients with a recurrent disc herniation have been treated successfully with both reoperative discectomy and reoperative discectomy combined with fusion. In patients with a recurrent lumbar disc herniation with associated spinal deformity, instability, or associated chronic low-back pain, consideration of fusion in addition to reoperative discectomy is recommended.


Oligoarginine Peptide Conjugated to BSA Improves Cell Penetration of Gold Nanorods and Nanoprisms for Biomedical Applications.
Gold nanoparticles (AuNPs) have been shown to be outstanding tools for drug delivery and biomedical applications, mainly owing to their colloidal stability, surface chemistry, and photothermal properties. The biocompatibility and stability of nanoparticles can be improved by capping the nanoparticles with endogenous proteins, such as albumin. Notably, protein coating of nanoparticles can interfere with and decrease their cell penetration. Therefore, in the present study, we functionalized albumin with the r8 peptide (All-D, octaarginine) and used it for coating NIR-plasmonic anisotropic gold nanoparticles. Gold nanoprisms (AuNPrs) and gold nanorods (AuNRs) were coated with bovine serum albumin (BSA) previously functionalized using a cell penetrating peptide (CPP) with the r8 sequence (BSA-r8). The effect of the coated and r8-functionalized AuNPs on HeLa cell viability was assessed by the MTS assay, showing a low effect on cell viability after BSA coating. Moreover, the internalization of the nanostructures into HeLa cells was assessed by confocal microscopy and transmission electron microscopy (TEM). As a result, both nanoconstructs showed an improved internalization level after being capped with BSA-r8, in contrast to the BSA-functionalized control, suggesting the predominant role of CPP functionalization in cell internalization. Thus, our results validate both novel nanoconstructs as potential candidates to be coated by endogenous proteins and functionalized with a CPP to optimize cell internalization. In a further approach, coating AuNPs with CPP-functionalized BSA can broaden the possibilities for biomedical applications by combining their optical properties, biocompatibility, and cell-penetration abilities.


Castor bean allergy in the upholstery department of a furniture factory.
In this study, undertaken to identify the cause of allergy in several upholstery workers in a furniture factory, the workers were handling several different materials, including glue, silicone spray, upholstery fabrics, and felt. Radio-allergo-sorbent test (RAST) assays showed that sera from sensitised workers contained specific IgE towards the felt; however, further investigations using RAST showed that the allergen was not the felt itself but a contaminant of the felt. The felt was manufactured from sacks, some of which had been used to store castor beans. The sera with raised IgE to the felt also had raised IgE to the castor bean extract. By means of RAST inhibition we confirmed that castor bean allergens in the felt were solely responsible for the raised IgE in the sera. The in-vitro RAST results were found to correlate well with the in-vivo pick tests and clinical symptoms.


Kinetic analysis and substrate specificity of Escherichia coli dimethyl sulfoxide reductase.
We have characterized the substrate specificity of dimethyl sulfoxide reductase (DmsABC) of Escherichia coli by determining Km and Kcat values for 22 different substrates. The enzyme has a very broad substrate specificity. The Km values varied 470-fold, while Kcat values varied only 20-fold, implicating Km as the major determinant of Kcat/Km values. Sulfoxides and pyridine N-oxide exhibited the lowest Km values, followed by aliphatic N-oxides. The Kcat values for these compounds also followed the same pattern. Substitution at the 2 or 3 position of the pyridine N-oxide ring had little effect on Km while substitution at the 4 position had a greater effect, and increased Km. Negatively charged substrates were poorly accepted. A few compounds that are not S- or N-oxides were also reduced by the enzyme. Most compounds reduced by DmsABC were not toxic to E. coli under anaerobic growth conditions, and E. coli was able to use many of these compounds anaerobically as terminal electron acceptors in the presence of glycerol. Anaerobic growth on sulfoxides is solely due to DmsABC expression. However, there appears to be another as yet unidentified terminal reductase capable of using pyridine N-oxides as terminal electron acceptors.


Hemostatic interference of Indian king cobra (Ophiophagus hannah) Venom. Comparison with three other snake venoms of the subcontinent.
Unlike Naja naja, Bungarus caeruleus, Echis carinatus, and Daboia/Vipera russellii venoms, Ophiophagus hannah venom is medically ignored in the Indian subcontinent. Being the biggest poisonous snake, O. hannah has been presumed to inject several lethal doses of venom in a single bite. Lack of therapeutic antivenom to O. hannah bite in India makes any attempt to save the victim a difficult exercise. This study was initiated to compare O. hannah venom with the above said venoms for possible interference in hemostasis. Ophiophagus hannah venom was found to actively interfere in hemostatic stages such as fibrin clot formation, platelet activation/aggregation, and fibrin clot dissolution. It decreased partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin clotting time (TCT). These activities are similar to that shown by E. carinatus and D. russellii venoms, and thus O. hannah venom was found to exert procoagulant activity through the common pathway of blood coagulation, while N. naja venom increased aPTT and TCT but not PT, and hence it was found to exert anticoagulant activity through the intrinsic pathway. Venoms of O. hannah, E. carinatus, and D. russellii lack plasminogen activation property as they do not hydrolyze azocasein, while they all show plasmin-like activity by degrading the fibrin clot. Although N. naja venom did not degrade azocasein, unlike other venoms, it showed feeble plasmin-like activity on fibrin clot. Venom of E. carinatus induced clotting of human platelet rich plasma (PRP), while the other three venoms interfered in agonist-induced platelet aggregation in PRP. Venom of O. hannah least inhibited the ADP induced platelet aggregation as compared to D. russellii and N. naja venoms. All these three venoms showed complete inhibition of epinephrine-induced aggregation at varied doses. However, O. hannah venom was unique in inhibiting thrombin induced aggregation.


Adherence, adverse drug reactions, and discontinuation associated with adverse drug reactions of HIV post-exposure prophylaxis: a meta-analysis based on cohort studies.
Objective: Evaluate the profiles of post-exposure prophylaxis (PEP) adherence, adverse drug reactions (ADRs), and discontinuation associated with ADRs to provide information for further PEP program improvement and increase adherence to PEP.Methods: The Web of Science, PubMed, Embase, and the Cochrane Library were searched for cohort studies reporting data related to PEP adherence or ADRs (PROSPERO, CRD42022385073). Pooled estimates of adherence, the incidence of ADRs and discontinuation associated with ADRs, and their 95% confidence intervals (CI) were calculated separately for the included literature using random effects models. For substantial heterogeneity, meta-regression and subgroup analyses were conducted to explore sources of heterogeneity.Results: Overall adherence was 58.4% (95% CI: 50.9%-65.8%), with subgroup analysis showing differences in adherence across samples, with the highest adherence among men who had sex with men (MSM) (72.4%, 95% CI: 63.4%-81.3%) and the lowest adherence among survivors of sexual assault (SAs) (41.7%, 95% CI: 28.0%-55.3%). The incidence of ADRs was 60.3% (95% CI: 50.3%-70.3%), and the prevalence of PEP discontinuation associated with ADRs was 32.7% (95% CI: 23.7%-41.7%), with subgroup analyses revealing disparities in the prevalence of discontinuation associated with ADRs among samples with different drug regimens. Time trend analysis showed a slight downward trend in the incidence of ADRs and PEP discontinuation associated with ADRs.Conclusion: Adherence to PEP was less than 60% across samples, however, there was significant heterogeneity depending on the samples. SAs had the lowest adherence and the highest incidence of PEP discontinuation. Ongoing adherence education for participants, timely monitoring, and management of ADRs may improve adherence.


Post-infectious Proliferative Glomerulonephritis with Monoclonal Immunoglobulin G Deposits Associated with Complement Factor H Mutation.
A 55-year-old man developed rapidly progressive glomerulonephritis and nephrotic syndrome. A kidney biopsy specimen showed diffuse proliferative and crescentic glomerulonephritis with monoclonal IgG1κ, humps, and nephritis-associated plasmin receptor, indicating infection-associated proliferative glomerulonephritis with monoclonal immunoglobulin G deposits (PGNMID). Despite dialysis-dependent renal failure, symptomatic therapy resulted in spontaneous recovery of the renal function, mimicking post-infectious glomerulonephritis (PIGN). A heterozygous complement factor H mutation was detected by comprehensive genetic testing of alternative pathway regulatory genes, which might lead to persistent infection-triggered alternative pathway activation and account for severe glomerulonephritis. Post-infectious PGNMID and PIGN might share common clinical presentations and pathogenesis related to the complement pathway.


Bone metabolism in idiopathic juvenile osteoporosis: a case report.
A previously healthy 12-year-old boy developed pain on walking and x-rays showed osteoporosis. Over the next 2 years deterioration occurred, the condition became extremely severe, and he was confined to a wheelchair. After 5 years, marked kyphoscoliosis and pigeon chest deformity were present and little increase in height occurred. A wheelchair accident at the age of 17 resulted in several major long bone fractures. Iliac crest biopsies were taken at ages 15 and 17, and subjected to quantitative histology. A histochemical technique for osteoclast recognition by acid phosphatase activity showed resorption parameters to be normal. Double tetracycline labeling and histochemical identification of osteoblasts showed no abnormality of endosteal bone formation. Because of "coupling" of endosteal formation and resorption, these measurements might primarily reflect bone turnover. Failure of periosteal bone formation as shown by failure of radial growth of long bones and of epiphyseal growth was clearly evident. It is likely that osteoporosis developed in this patient due to a reduction in bone formation of unknown etiology rather than by increased bone resorption.


Long-term survival with growth hormone replacement after liver transplantation of pediatric nonalcoholic steatohepatitis complicating acquired hypopituitarism.
Nonalcoholic steatohepatitis (NASH) is the most severe form of nonalcoholic fatty liver disease (NAFLD). In adult patients, liver transplantation (LT) is the treatment of choice for end-stage liver disease secondary to NASH. However, little information is available regarding outcomes of LT in pediatric patients with NASH. We describe here a pediatric patient with NASH associated with hypopituitarism who underwent living donor liver transplantation (LDLT). An 11-year-old boy was diagnosed with a pituitary tumor, which was removed by trans-interhemispheric approach following bifrontal craniotomy. Histopathological examination revealed a mature teratoma. Eighteen months later, magnetic resonance imaging showed recurrence of the pituitary tumor, which was found to be a germinoma. He underwent 3 months of chemoradiotherapy, with a complete response. He gradually became obese, with elevated transaminase levels. At age 15 years, he developed fatigue and dyspnea and was found to have liver cirrhosis secondary to NASH with severe hepatopulmonary syndrome. He underwent LDLT using a right liver graft from his mother. Twelve months later, abdominal computed tomography showed recurrence of NAFLD. Five years after the LDLT, transaminases were slightly elevated. Growth hormone replacement therapy was started, reducing transaminase levels to their normal ranges. Ten years after LDLT, fatty liver remains stable, although his body mass index has not been reduced. Growth hormone replacement therapy may be effective in graft maintenance. This is the first case report of a patient with maintained stable liver function 10 years after LDLT for pediatric NASH.


Interferon-gamma release assay versus tuberculin skin test for latent tuberculosis infection among HIV patients in Brazil.
Patients HIV+ attending in a reference clinic, Southern Brazil. To compare the interferon-gamma-release assay (IGRA - QuantiFERON(®) TB Gold In-Tube) with the tuberculin skin test (TST - PPD-Rt 23) for latent tuberculosis infection (LTBI) in patients with HIV. Cohort study. Patients were simultaneously submitted to the TST and blood collection for the IGRA. A total of 140 subjects were included. Nine (6.4%) were IGRA+/TST+, 12 (8.6%) were IGRA+/TST-, 4 (3%) were IGRA-/TST+, and 115 (82%) IGRA-/TST-. There was poor agreement between tests (kappa=0.2), and no correlation between these results and CD4+ T lymphocyte counts. During follow-up, one patient with negative results on both tests died from sepsis, and another with discordant results (IGRA+/TST-) exhibited TST seroconversion. Compared to the TST, IGRA showed a sensitivity and specificity of 69% and 90%, respectively. The IGRA detected 8% more positive results than the TST. All patients were followed up for 2 years. The higher accuracy of the IGRA would result in LTBI treatments being administered to patients who would have otherwise been overlooked, decreasing the number of active tuberculosis cases. The long-term survival of HIV carriers requires further evaluation.


Laparoscopic skills acquisition: a study of simulation and traditional training.
Training in basic laparoscopic skills can be undertaken using traditional methods, where trainees are educated by experienced surgeons through a process of graduated responsibility or by simulation-based training. This study aimed to assess whether simulation trained individuals reach the same level of proficiency in basic laparoscopic skills as traditional trained participants when assessed in a simulated environment. A prospective study was undertaken. Participants were allocated to one of two cohorts according to surgical experience. Participants from the inexperienced cohort were randomized to receive training in basic laparoscopic skills on either a box trainer or a virtual reality simulator. They were then assessed on the simulator on which they did not receive training. Participants from the experienced cohort, considered to have received traditional training in basic laparoscopic skills, did not receive simulation training and were randomized to either the box trainer or virtual reality simulator for skills assessment. The assessment scores from different cohorts on either simulator were then compared. A total of 138 participants completed the assessment session, 101 in the inexperienced simulation-trained cohort and 37 on the experienced traditionally trained cohort. There was no statistically significant difference between the training outcomes of simulation and traditionally trained participants, irrespective of the simulator type used. The results demonstrated that participants trained on either a box trainer or virtual reality simulator achieved a level of basic laparoscopic skills assessed in a simulated environment that was not significantly different from participants who had been traditionally trained in basic laparoscopic skills.


Kinetic mechanism and metabolic role of pyruvate phosphate dikinase from Entamoeba histolytica.
The kinetic mechanism and the metabolic role of pyruvate phosphate dikinase from Entamoeba histolytica were investigated. The initial velocity patterns in double reciprocal plots were parallel for the phosphoenolpyruvate/AMP and phosphoenolpyruvate/pyrophosphate substrate pairs and intersecting for the AMP/pyrophosphate pair. This suggests a kinetic mechanism with two independent reactions. The rate of ATP synthesis at saturating and equimolar concentrations of phosphoenolpyruvate, AMP, and pyrophosphate was inhibited by phosphate, which is consistent with an ordered steady-state mechanism. Enzyme phosphorylation by [(32)P(i)]pyrophosphate depends on the formation of a ternary complex between AMP, pyrophosphate, and pyruvate phosphate dikinase. In consequence, the reaction that involves the AMP/pyrophosphate pair follows a sequential steady-state mechanism. The product inhibition patterns of ATP and phosphate versus phosphoenolpyruvate were noncompetitive and uncompetitive, respectively, suggesting that these products were released in an ordered process (phosphate before ATP). The ordered release of phosphate and ATP and the noncompetitive inhibition patterns of pyruvate versus AMP and versus pyrophosphate also supported the sequential kinetic mechanism between AMP and pyrophosphate. Taken together, our data provide evidence for a uni uni bi bi pingpong mechanism for recombinant pyruvate phosphate dikinase from E. histolytica. The Delta G value for the reaction catalyzed by pyruvate phosphate dikinase (+2.7 kcal/mol) determined under near physiological conditions indicates that the synthesis of ATP is not thermodynamically favorable in trophozoites of E. histolytica.


Monkey brain damage from radiation in the therapeutic range.
Twelve Macaca mulatta monkeys received 200 rads of supervoltage radiation to the whole brain per day, 5 days a week. The course in 4 monkeys was 4 weeks for a total dose of 4000 rads; in 4 monkeys, 6 weeks for 6000 rads; and in 4 monkeys, 8 weeks for 8000 rads. Four unirradiated monkeys served as controls. One from each group, sacrificed at 6 and 12 months from start of irradiation, are reported here. The results from 4000 rads were negligible; those from 8000 rads, profound, with gross brain destruction. The results from 6000 rads, within the therapeutic range, included at 6 months punctate necrotic lesions, 1 mm or less, widely scattered but with a predilection for the forebrain white matter. The reaction to these lesions ranged from an early macrophage response to calcification. Some were accompanied by focal edema. There were occasional examples of vascular endothelial proliferation. In addition, there were patches of dilated capillaries or telangiectasia. Twelve months after 6000 rads there were a few mineralized lesions and innumerable minute deposits of calcium and iron. A more active process was suggested by widely disseminated areas of telangiectasia, 6 to 12 mm in extent. The clinical course from this exposure included papilledema from the third to the sixth month and depressed visual evoked response accompanied by delta activity in the electroencephalogram from the sixth to the twelfth month.


Sedimentation instabilities: impact of the fluid compressibility and viscosity.
The effect of an interstitial fluid on the mixing of sedimenting grains is studied numerically in a closed rectangular Hele-Shaw cell. We investigate the impact of the fluid compressibility and fluid viscosity on the dynamics and structures of the granular Rayleigh-Taylor instability. First we discuss the effect of the fluid compressibility on the initial fluid pressure evolution and on the dynamics of the particles. Here, the emerging patterns do not seem highly affected by the compressibility change studied. To characterize the patterns and motion the combined length of the particle trajectories in relation to the movement of the center of mass is analyzed, and the separation of particle pairs is measured as a function of the fluid viscosity.


Giant adrenocortical carcinoma with 27-month disease-free survival by surgical resection alone: a case report.
Adrenocortical cancer (ACC) is a rare disease with an estimated incidence of 1-2/million/year. The tumour stage and completeness of surgical resection have the biggest impact on survival. Whereas stage I-II patients survive in 55-64% of cases, only 0-5% of patients with stage IV disease are still alive at 5 years. A median survival of 33 months can be expected after curative surgery. Incomplete surgery leads to a significant drop in survival. We present a 40-year-old man who underwent a technically demanding complete surgical excision of a giant (26 cm, 2372 g) ACC and experienced a 27-month disease-free survival without any systemic treatment. Detailed description of the surgical anatomy in relation to tumour size and patient body constitution is provided. The surgical strategy and exposure pitfalls under such extreme circumstances are discussed. To achieve R0 resection in locally advanced disease, en bloc resection with neighbouring organs is widely recommended. Giant tumours may however pose a technical challenge due to space constraints.


Transcriptional profiling of pediatric cholestatic livers identifies three distinct macrophage populations.
Limited understanding of the role for specific macrophage subsets in the pathogenesis of cholestatic liver injury is a barrier to advancing medical therapy. Macrophages have previously been implicated in both the mal-adaptive and protective responses in obstructive cholestasis. Recently two macrophage subsets were identified in non-diseased human liver; however, no studies to date fully define the heterogeneous macrophage subsets during the pathogenesis of cholestasis. Here, we aim to further characterize the transcriptional profile of macrophages in pediatric cholestatic liver disease. We isolated live hepatic immune cells from patients with biliary atresia (BA), Alagille syndrome (ALGS), and non-cholestatic pediatric liver by fluorescence activated cell sorting. Through single-cell RNA sequencing analysis and immunofluorescence, we characterized cholestatic macrophages. We next compared the transcriptional profile of pediatric cholestatic and non-cholestatic macrophage populations to previously published data on normal adult hepatic macrophages. We identified 3 distinct macrophage populations across cholestatic liver samples and annotated them as lipid-associated macrophages, monocyte-like macrophages, and adaptive macrophages based on their transcriptional profile. Immunofluorescence of liver tissue using markers for each subset confirmed their presence across BA (n = 6) and ALGS (n = 6) patients. Cholestatic macrophages demonstrated reduced expression of immune regulatory genes as compared to normal hepatic macrophages and were distinct from macrophage populations defined in either healthy adult or pediatric non-cholestatic liver. We are the first to perform single-cell RNA sequencing on human pediatric cholestatic liver and identified three macrophage subsets with distinct transcriptional signatures from healthy liver macrophages. Further analyses will identify similarities and differences in these macrophage sub-populations across etiologies of cholestatic liver disease. Taken together, these findings may allow for future development of targeted therapeutic strategies to reprogram macrophages to an immune regulatory phenotype and reduce cholestatic liver injury.


Primary squamous cell carcinoma of the liver concomitant with primary colon cancer: report of a case.
A 55-year-old Japanese female was admitted to our hospital to treat colon cancer. Computed tomography revealed a 2.6 × 2.0 cm liver mass considered to be liver metastasis. She synchronously underwent right colectomy with D3 lymph node dissection and subsegmentectomy 8 under the diagnosis of advanced colon cancer with liver metastasis. The pathology examination revealed the liver nodule was pure squamous cell carcinoma (SCC), whereas histology of colon cancer was a well differentiated tubular adenocarcinoma containing no squamous component. The patient underwent intensive checkup by imaging for a primary site of SCC. However, no lesion considered as possible primary site of SCC was found. Therefore, the liver nodule was finally diagnosed as a primary hepatic SCC. Primary SCC of the liver is a rare and high-grade malignant tumor. Recurrent multiple liver nodule was found at 13 months after surgery and the patient died of cancer 17 months after surgery.


[Turbinella angulata and Busyconperversum (Mesogasteropoda: Turbinellidae and Melongenidae) population and reproductive dynamics in the Campeche Bank, Mexico].
Turbinella angulata and Busycon perversum are two marine gastropods that support the 90% of conch fisheries in the Gulf of Mexico, nevertheless there is no information available to support a management strategy for both species. The aim of this work was to obtain preliminary fishery information to promote management actions for both species in the Campeche Bank. The population of conchs was sampled in 12 transects (150x1.5m) by SCUBA diving from April 2008 to March 2010. All conchs were collected and siphonal length (SL) was measured. These samples were complemented with data from the commercial catches, analyzing a total of 2 832 individuals of T angulata. Siphonal length varied between 63 and 282mm. Sex ratio was of 0.98:1 female:male. The von Bertalanffy growth equation parameters were: L infinity =346mm; K=0.30 and t(0)=-0.24. Spawning extended from January to May with a long resting stage from June to September for over 80% of the adult population. The first gonadic maturity (L50) was at 210mm (SL) for females and 200mm for males. For B. perversum a total of 1655 individuals were analyzed. Siphonal length varied between 78 and 291mm with significant differences between male and female (p<0.05). Sex ratio was of 1:0.25 female:male. The growth parameters obtained were: Linifinity=360mm; K=0.35 and t(0)=-0.19. The spawning period was from August to December with resting stage from January to April. The L50 was 215mm (LS) for females and 190mm for males. Both species presented one recruitment pulse. These results will be useful to design management schemes based on population dynamics and reproductive attributes.


Coordination of Care Around Surgery for Colon Cancer: Insights From National Patterns of Physician Encounters With Medicare Beneficiaries.
To improve care coordination for complex cancers, it is critical to establish a more nuanced understanding of the types of providers involved. As the number of provider types increases, strategies to support cancer care coordination must adapt to a greater variety of information needs, communication styles, and treatment strategies. We categorized providers into 11 types, using National Provider Identifier specialties. Using Medicare claims, we counted the number of unique combinations of provider types billed during preoperative, operative, and postdischarge care for colon cancer surgery and assessed how this count varies across hospitals. The study included 70,567 beneficiaries in fee-for-service Medicare A and B for 6 months before and 60 days after an admission for colectomy for colon cancer between 2008 and 2011. We observed 1,554 preoperative provider-type combinations, 975 operative combinations, and 1,571 postdischarge combinations. The three most common combinations in the preoperative phase were general medicine only, other medical specialists only, and general medicine and other medical specialists. In the operative phase, the three most common combinations were primary surgery, anesthesiology, and pathology; general medicine, other medical specialists, radiology, primary surgery, anesthesiology, and pathology; and other medical specialists, radiology, primary surgery, anesthesiology, and pathology. In the postdischarge phase, the three most common combinations were general medicine, general medicine and other medical specialists, and general medicine and oncology. On average, each hospital had 15 preoperative, 11 operative, and 15 postoperative combinations. High-volume, larger, teaching, urban, and noncritical access hospitals had more combinations in all phases. Many provider-type combinations are involved in colon cancer surgery care. Substantial variation exists across hospitals types, suggesting that certain hospitals need additional resources and more flexible infrastructure to coordinate care.


A novel 1,4-naphthoquinone-derived compound induces apoptotic cell death in breast cancer cells.
Breast cancer is the most-diagnosed cancer type among women. The triple-negative subtype is an especially aggressive type of breast cancer. Although chemotherapy is almost the only option for the treatment of triple-negative breast cancer (TNBC), currently used chemotherapeutics are not effective enough, considering the poor survival rate of patients. Therefore, novel compounds need to be developed to improve survival rates. It has been known that quinonic compounds, which are found in nature, have antibacterial, antifungal, and antitumorigenic properties. Naphthoquinones are members of the quinone family and are widely used in research due to their promising properties. In this study, we evaluated the cytotoxic activity of a novel naphthoquinone-derived compound (1,4-naphthoquinone (1,4-NQ)) against two different breast cancer cells: a hormone-responsive cell line (MCF-7) and a triple-negative cell line (MDA-MB-231). As a result, 1,4-NQ decreased cell viability in both tested cell lines in a dose-dependent manner. Increased apoptotic markers (presence of pyknotic nuclei, annexin-V positivity, caspase 3/7 activity, and decreased mitochondrial membrane potential) and DNA damage were especially observed in MDA-MB-231 cells after treatment with the compound. Considering the promising cytotoxic effect of the compound, 1,4-NQ needs further evaluation as a potential candidate for the treatment of TNBC.


Does blood flow accurately predict thrombosis or failure of hemodialysis synthetic grafts? A meta-analysis.
A number of studies have reported that a single low blood flow (Qa) measurement in synthetic hemodialysis grafts predicts thrombosis or failure. In a meta-analysis of these studies, we computed receiver operating characteristic (ROC) curves that evaluated the predictive accuracy of a Qa measurement. The ROC curves plotted sensitivity versus false-positive rate for predicting thrombosis or failure at different Qa thresholds. A perfect predictor has an area under the curve (AUC) of 1.0, whereas a predictor with no discriminative ability has an AUC of 0.5. We identified studies through a literature search and included our own unpublished data. A random-effects model was used to combine the ROC curves from different studies. Of 19 identified studies, 12 were suitable for computing binormal ROC curves (6 predicted thrombosis; 6 predicted failure). The studies measured Qa and then observed outcome during periods of 1.5 to more than 6 months. The combined AUCs from these studies indicate Qa was a relatively poor predictor, with 0.70 +/- 0. 04 (range, 0.61 to 0.84) for thrombosis and 0.76 +/- 0.07 (range, 0. 62 to 0.90) for failure. The wide range of AUCs also shows there was much heterogeneity between studies. We conclude that a single Qa measurement does not appear to have enough accuracy to be a clinically useful predictor of graft thrombosis or failure. Serial Qa measurements and identification of factors that caused heterogeneity between studies may be needed to achieve sufficient accuracy.


Strategies to Identify and Recruit Women at High Risk for Breast Cancer to a Randomized Controlled Trial of Web-based Decision Support Tools.
We evaluated strategies to identify and recruit a racially/ethnically diverse cohort of women at high-risk for breast cancer to a randomized controlled trial (RCT). We enrolled 300 high-risk women and 50 healthcare providers to a RCT of standard educational materials alone or in combination with web-based decision support tools. We implemented five strategies to identify high-risk women: (i) recruitment among patients previously enrolled in a study evaluating breast cancer risk; (ii) automated breast cancer risk calculation using information extracted from the electronic health record (EHR); (iii) identification of women with atypical hyperplasia or lobular carcinoma in situ (LCIS) using International Classification of Diseases (ICD)-9/10 diagnostic codes; (iv) clinical encounters with enrolled healthcare providers; (v) recruitment flyers/online resources. Breast cancer risk was calculated using either the Gail or Breast Cancer Surveillance Consortium (BCSC) models. We identified 6,229 high-risk women and contacted 3,459 (56%), of whom 17.2% were identified from prior study cohort, 37.5% through EHR risk information, 14.8% with atypical hyperplasia/LCIS, 29.0% by clinical encounters, and 1.5% through recruitment flyers. Women from the different recruitment sources varied by age and 5-year invasive breast cancer risk. Of 300 enrolled high-risk women, 44.7% came from clinical encounters and 27.3% from prior study cohort. Comparing enrolled with not-enrolled participants, there were significant differences in mean age (57.2 vs. 59.1 years), proportion of non-Whites (41.5% vs. 54.8%), and mean 5-year breast cancer risk (3.0% vs. 2.3%). We identified and successfully recruited diverse high-risk women from multiple sources. These strategies may be implemented in future breast cancer chemoprevention trials. We describe five strategies to identify and successfully recruit a large cohort of racially/ethnically diverse high-risk women from multiple sources to a randomized controlled trial evaluating interventions to increase chemoprevention uptake. Findings could inform recruitment efforts for future breast cancer prevention trials to increase recruitment yield of high-risk women.


Defining a learning curve for laparoscopic colorectal resections.
The purpose of this review was to define the learning curve for laparoscopic colorectal resections. A prospectively accumulated, computerized database of all laparoscopic colorectal resections performed by three surgeons between April 1991 and March 1999 was reviewed. A total of 461 consecutive resections were evenly distributed among three surgeons (141, 155, and 165). Median operating time was 180 minutes for Cases 1 to 30 in each surgeon's experience and declined to a steady state (150-167.5 minutes) for Cases 31 and higher. Subsequently, Cases 1 to 30 were considered "early experience," whereas Cases 31 and higher were combined as "late experience" for statistical analysis. There were no significant differences between patients undergoing resections in the early experience and those undergoing resections in the late experience with respect to age, weight, or proportion of patients with malignancy, diverticulitis, or inflammatory bowel disease. There were greater proportions of males (42 vs. 54 percent, P = 0.046) and rectal resections performed (14 vs. 32 percent, P = 0.002) in the late experience. Trends toward declining rates of intraoperative complications (9 vs. 7 percent, P = 0.70) and conversion to open surgery (13.5 vs. 9.7 percent, P = 0.39) were observed with experience. Median operating time (180 vs. 160 minutes, P < 0.001) and overall length of postoperative hospital stay (6.5 vs. 5 days, P < 0.001) declined significantly with experience. There was no difference in the rate of postoperative complications between early and late experience (30 vs. 32 percent, P = 0.827). The learning curve for performing colorectal resections was approximately 30 procedures in this study, based on a decline in operating time, intraoperative complications, and conversion rate. Learning was also extended to clinical care because it was appreciated that patients could be discharged to their homes more quickly.


Optimal intervention strategies to mitigate the COVID-19 pandemic effects.
Governments across the world are currently facing the task of selecting suitable intervention strategies to cope with the effects of the COVID-19 pandemic. This is a highly challenging task, since harsh measures may result in economic collapse while a relaxed strategy might lead to a high death toll. Motivated by this, we consider the problem of forming intervention strategies to mitigate the impact of the COVID-19 pandemic that optimize the trade-off between the number of deceases and the socio-economic costs. We demonstrate that the healthcare capacity and the testing rate highly affect the optimal intervention strategies. Moreover, we propose an approach that enables practical strategies, with a small number of policies and policy changes, that are close to optimal. In particular, we provide tools to decide which policies should be implemented and when should a government change to a different policy. Finally, we consider how the presented results are affected by uncertainty in the initial reproduction number and infection fatality rate and demonstrate that parametric uncertainty has a more substantial effect when stricter strategies are adopted.


Comparison of envelope-related genes in unicellular and filamentous cyanobacteria.
To elucidate the evolution of cyanobacterial envelopes and the relation between gene content and environmental adaptation, cell envelope structures and components of unicellular and filamentous cyanobacteria were analyzed in comparative genomics. Hundreds of envelope biogenesis genes were divided into 5 major groups and annotated according to their conserved domains and phylogenetic profiles. Compared to unicellular species, the gene numbers of filamentous cyanobacteria expanded due to genome enlargement effect, but only few gene families amplified disproportionately, such as those encoding waaG and glycosyl transferase 2. Comparison of envelope genes among various species suggested that the significant variance of certain cyanobacterial envelope biogenesis genes should be the response to their environmental adaptation, which might be also related to the emergence of filamentous shapes with some new functions.


Loss of heterozygosity studies in squamous cell carcinomas of the head and neck.
Loss of heterozygosity (LOH) studies have been pivotal in identifying tumor suppressor genes involved in the pathogenesis of a number of cancers. In squamous cell carcinomas of the head and neck region (SCCHN), LOH studies using the Southern blot technique are scarce. SCCHNs were obtained immediately after surgical resection from 78 patients. Histologic confirmation was made by frozen section and tumors with less than 50% malignant cells were excluded. DNA was digested with restriction enzymes, and after Southern blotting the membranes were hybridized with radio-labeled probes. Chromosome arms analyzed included 1p, 3p, 4p, Sq, 8p, lOp, 11p, 11q, 13q, 17p, 17q, 18q, 21q, and 22q. The average rate LOH was 25% per chromosome arm. Significantly higher rates of LOH were observed for chromosome arms 5q (56%) and 17p (45%). Other investigators have reported high rates of LOH for the H- ras-1 locus, and chromosome arms 11p, 11q, and 13q. However, these results were not confirmed in this study. For patients with stage 1 or 2 tumors, the overall LOH rate was 13%, and for patients with stage 3 or 4 disease the rate was 23%. This difference was statistically significant (p < 0.025). tumors progress to higher stages, they appear to accumulate an increasing number of genetic abnormalities. Chromosome arms 5q and 17p contain tumor suppressor genes which are likely to be involved in the pathogenesis of SCCHN: