Cathepsin K Deficiency Prevents the Aggravated Vascular Remodeling Response to Flow Cessation in ApoE-/- Mice.
Cathepsin K (catK) is a potent lysosomal cysteine protease involved in extracellular matrix (ECM) degradation and inflammatory remodeling responses. Here we have investigated the contribution of catK deficiency on carotid arterial remodeling in response to flow cessation in apoE-/- and wild type (wt) background. Ligation-induced hyperplasia is considerably aggravated in apoE-/- versus wt mice. CatK protein expression was significantly increased in neointimal lesions of apoE-/- compared with wt mice, suggesting a role for catK in intimal hyperplasia under hyperlipidemic conditions. Surprisingly, CatK deficiency completely blunted the augmented hyperplastic response to flow cessation in apoE-/-, whereas vascular remodeling in wt mice was unaffected. As catK deficiency did neither alter lesion collagen content and elastic laminae fragmentation in vivo, we focused on effects of catK on (systemic) inflammatory responses. CatK deficiency significantly reduced circulating CD3 T-cell numbers, but increased the regulatory T cell subset in apoE-/- but not wt mice. Moreover, catK deficiency changed CD11b+Ly6G-Ly6C high monocyte distribution in apoE-/- but not wt mice and tended to favour macrophage M2a polarization. In conclusion, catK deficiency almost completely blunted the increased vascular remodeling response of apoE-/- mice to flow cessation, possibly by correcting hyperlipidemia-associated pro-inflammatory effects on the peripheral immune response.


A predictive model of the temperature-dependent inactivation of coronaviruses.
The COVID-19 pandemic has stressed healthcare systems and supply lines, forcing medical doctors to risk infection by decontaminating and reusing single-use personal protective equipment. The uncertain future of the pandemic is compounded by limited data on the ability of the responsible virus, SARS-CoV-2, to survive across various climates, preventing epidemiologists from accurately modeling its spread. However, a detailed thermodynamic analysis of experimental data on the inactivation of SARS-CoV-2 and related coronaviruses can enable a fundamental understanding of their thermal degradation that will help model the COVID-19 pandemic and mitigate future outbreaks. This work introduces a thermodynamic model that synthesizes existing data into an analytical framework built on first principles, including the rate law for a first-order reaction and the Arrhenius equation, to accurately predict the temperature-dependent inactivation of coronaviruses. The model provides much-needed thermal decontamination guidelines for personal protective equipment, including masks. For example, at 70 °C, a 3-log (99.9%) reduction in virus concentration can be achieved, on average, in 3 min (under the same conditions, a more conservative decontamination time of 39 min represents the upper limit of a 95% interval) and can be performed in most home ovens without reducing the efficacy of typical N95 masks as shown in recent experimental reports. This model will also allow for epidemiologists to incorporate the lifetime of SARS-CoV-2 as a continuous function of environmental temperature into models forecasting the spread of the pandemic across different climates and seasons.


Motor functions and adaptive behaviour in children with childhood apraxia of speech.
Undiagnosed motor and behavioural problems have been reported for children with childhood apraxia of speech (CAS). This study aims to understand the extent of these problems by determining the profile of and relationships between speech/non-speech oral, manual and overall body motor functions and adaptive behaviours in CAS. Eighteen children (five girls and 13 boys) with CAS, 4 years 4 months to 10 years 6 months old, participated in this study. The assessments used were the Verbal Motor Production Assessment for Children (VMPAC), Bruininks-Oseretsky Test of Motor Proficiency (BOT-2) and Adaptive Behaviour Assessment System (ABAS-II). Median result of speech/non-speech oral motor function was between -1 and -2 SD of the mean VMPAC norms. For BOT-2 and ABAS-II, the median result was between the mean and -1 SD of test norms. However, on an individual level, many children had co-occurring difficulties (below -1 SD of the mean) in overall and manual motor functions and in adaptive behaviour, despite few correlations between sub-tests. In addition to the impaired speech motor output, children displayed heterogeneous motor problems suggesting the presence of a global motor deficit. The complex relationship between motor functions and behaviour may partly explain the undiagnosed developmental difficulties in CAS.


Distally Based Medial Hemisoleus Muscle Flap: Anatomic and Angiographic Study of 18 Lower Limbs.
The distally based medial hemisoleus (MHS) flap was found useful for repairing soft-tissue defects of the lower third of the leg; however, its reliability is controversial. We used a combination of static and dynamic techniques to investigate the vascular supply of distally based MHS muscle flaps to better establish their use in repair of lower-third leg defects. We performed an anatomic study of 18 cadaver legs. For 6 legs, we performed dynamic angiography, which allowed for obtaining MHS muscle radiographs after pulsed injection of contrast medium in distal pedicles. The mean length of MHS muscle was 25.4 cm, the mean width was 6.9 cm, and the mean surface area was 87.5 cm. A mean of 3 distal posterior tibial vascular pedicles was directly connected to this medial subunit. These pedicles were present in all 18 cadaver legs. We observed complete opacification of the 6 MHS muscles through distal pedicles. Radiography revealed opacification of a vascular path from 1 distal pedicle to 1 proximal vascular pedicle of the MHS muscle. The mean level of this main distal pedicle was 14.5 cm to the tip of the medial malleolus. The level was at 38.2%, on average, from the bottom of the entire tibia. The distally based MHS muscle flap has constant blood supply, so it could be a useful flap to repair soft-tissue defects of the lower third of the leg. Moreover, knowledge of the average location of the main distal pedicle can help in increasing the use of the distally based MHS flap.


A biomechanical assessment of the sliding motion of curling delivery in elite and subelite curlers.
The present study examined the technical characteristics of sliding performance from push-off until stone release in curling delivery. Five elite performance level curlers (> 7 years experience) and five subelite level curlers (< 3 years experience) were analyzed during the action of delivery of a curling stone. The joint angles, angular velocities, and moments of the body center of mass (COM) were determined based on three-dimensional kinematic data. The plantar pressure data were measured using a validated in-shoe system. The results indicated that the gliding time and horizontal velocity of the mass center of the body during the sliding phase were not significantly different between the elite and subelite groups. However, there were significant differences in the gliding distance and the rate of changes in velocity profiles of body COM between the two groups. The moment of the body COM from its relative position to the ankle of the support limb in the anterior/posterior direction was positive in elite curlers and negative in subelite curlers. In addition, larger ankle dorsiflexion and greater contact area of the sliding foot were observed in elite curlers. These data suggest a superior ability of elite curlers to maintain a regulated movement speed and balance control during the performance of a curling stone delivery.


Genetic predictors of glucocorticoid response in pediatric patients with inflammatory bowel diseases.
Glucocorticoids (GCs) are used in moderate-to-severe inflammatory bowel diseases (IBD) but their effect is often unpredictable. To determine the influence of 4 polymorphisms in the GC receptor [nuclear receptor subfamily 3, group C, member 1 (NR3C1)], interleukin-1β (IL-1β), and NACHT leucine-rich-repeat protein 1 (NALP1) genes, on the clinical response to steroids in pediatric patients with IBD. One hundred fifty-four young IBD patients treated with GCs for at least 30 days and with a minimum follow-up of 1 year were genotyped. The polymorphisms considered are the BclI in the NR3C1 gene, C-511T in IL-1β gene, and Leu155His and rs2670660/C in NALP1 gene. Patients were grouped as responder, dependant, and resistant to GCs. The relation between GC response and the genetic polymorphisms considered was examined using univariate, multivariate, and Classification and Regression Tree (CART) analysis. Univariate analysis showed that BclI polymorphism was more frequent in responders compared with dependant patients (P=0.03) and with the combined dependant and resistant groups (P=0.02). Moreover, the NALP1 Leu155His polymorphism was less frequent in the GC responsive group compared with resistant (P=0.0059) and nonresponder (P=0.02) groups. Multivariate analysis comparing responders and nonresponders confirmed an association between BclI mutated genotype and steroid response (P=0.030), and between NALP1 Leu155His mutant variant and nonresponders (P=0.033). An association between steroid response and male sex was also observed (P=0.034). In addition, Leu155His mutated genotype was associated with steroid resistance (P=0.034). Two CART analyses supported these findings by showing that BclI and Leu155His polymorphisms had the greatest effect on steroid response (permutation P value=0.046). The second CART analysis also identified age of disease onset and male sex as important variables affecting response. These results confirm that genetic and demographic factors may affect the response to GCs in young patients with IBD and strengthen the importance of studying high-order interactions for predicting response.


Herpes simplex virus detection by macroscopic reading after overnight incubation and immunoperoxidase staining.
Human diploid foreskin fibroblast cells grown in 24-well plates were inoculated with clinical specimens by centrifugation at 1,000 X g for 45 min. Cultures were incubated at 37 degrees C overnight, fixed, and stained with peroxidase-labeled monoclonal antibodies against herpes simplex virus types 1 and 2. Stained plaques of infected cells were large enough to be detected with the naked eye, and microscopic examination did not reveal any further positive specimens. The method was compared with standard isolation in human fibroblasts grown in shell vials and inoculated by centrifugation at 4,000 X g, observed microscopically for the occurrence of typical cytopathogenic effect three times a week for 10 days, and then typed by enzyme immunoassay. Of the 289 specimens tested, 105 were positive and 174 were negative by both methods. Six specimens were positive by standard isolation only, two of them containing varicella-zoster virus, and two specimens were stored frozen before being tested by immunoperoxidase staining. Two specimens found negative by standard isolation were positive by immunoperoxidase staining. For two specimens negative by immunoperoxidase staining, the standard isolation cultures were lost due to microbial contamination. Forty-two specimens found positive by standard isolation were clearly positive when stained only 8 h after inoculation. By standard isolation, positive results were reported on the average 3 to 4 days after inoculation, whereas by immunoperoxidase staining the result was available within less than 24 h. Immunoperoxidase staining of infected cells is a sensitive method for rapid laboratory diagnosis of herpes simplex virus infections, and 24-well plates are convenient for the handling of a large number of specimens.


Beneficial role of CD8+ T-cell reconstitution after HLA-haploidentical stem cell transplantation for high-risk acute leukaemias: results from a clinico-biological EBMT registry study mostly in the T-cell-depleted setting.
HLA-haploidentical haematopoietic stem cell transplantation (haplo-HSCT) is increasingly offered to patients with high-risk acute leukaemia. Unfortunately, haplo-HSCT is followed by a delayed immunoreconstitution. The aim of this EBMT registry study was to explore the clinical impact of lymphocyte subset counts after haplo-HSCT. We considered 144 leukaemic patients transplanted in the period 2001-2012. Pre-transplantation clinical variables and differential immune-cell counts (CD3, CD4, CD8 T cells, NK and B cells) measured before day 100 were evaluated for their capacity to predict overall survival, relapse mortality or non-relapse mortality (NRM). Negative prognostic factors for overall survival were advanced disease state at transplantation, host age and CMV seropositivity. Higher CD3, CD4 and CD8 counts were associated with a better overall survival and a lower NRM. Strikingly, when tested in multivariable analysis, higher CD3 and CD8 counts were still significantly associated with a lower NRM. These results indicate that an accelerated T-cell reconstitution correlates with less transplantation mortality, likely due to the protective role of T cells against viral infections. This observation suggests that CD8+ T-cell counts should be investigated as surrogate biomarkers of outcome in prospective haplo-HSCT trials.


[Trends in the development of psychotherapy in the USSR].
Psychotherapy, which is mainly directed th the personality and the social relations of the patients, is gaining increasing importance not only in psychiatry. Beyond neurotic diseases, it is an essential part in the treatment of additions, endogenous psychoses, cardiovascular diseases as well as in paediatrics, öncology and other clinical disciplines. Following the regulations of the Ministry of Health of the USSR, an extensive and systematic network of psychotherapeutical treatment centres for outpatients is being established. Psychotherapy is of particular importance in the field of rehabilitation. Besides, questions regarding the position of psychotherapy in medicine, of education and continued training and of the position of the clinical psychologist are dealt with.


atTic110 functions as a scaffold for coordinating the stromal events of protein import into chloroplasts.
The translocon of the inner envelope membrane of chloroplasts (Tic) mediates the late events in the translocation of nucleus-encoded preproteins into chloroplasts. Tic110 is a major integral membrane component of active Tic complexes and has been proposed to function as a docking site for translocation-associated stromal factors and as a component of the protein-conducting channel. To investigate the various proposed functions of Tic110, we have investigated the structure, topology, and activities of a 97.5-kDa fragment of Arabidopsis Tic110 (atTic110) lacking only the amino-terminal transmembrane segments. The protein was expressed both in Escherichia coli and Arabidopsis as a stable, soluble protein with a high alpha-helical content. Binding studies demonstrate that a region of the atTic110-soluble domain selectively associates with chloroplast preproteins at the late stages of membrane translocation. These data support the hypothesis that the bulk of Tic110 extends into the chloroplast stroma and suggest that the domain forms a docking site for preproteins as they emerge from the Tic translocon.


Involvement of the interleukin 2 pathway in the rearrangement and expression of both alpha/beta and gamma/delta T cell receptor genes in human T cell precursors.
In this report, we have undertaken the phenotypic, functional and molecular characterization of a minor (less than 5%) subpopulation of adult thymocytes regarded as the earliest intrathymic T-cell precursors. Pro-T cells were immunoselected and shown to express different hematopoietic cell markers (CD45, CD38, CD7, CD5) and some activation-related molecules (4F2, Tr, HLA class II), but lack conventional T cell antigens (CD2-1-3-4-8-). TCR-gamma RNA messages are already expressed at this early ontogenic stage, while alpha and beta chain TCR genes remain in germline configuration. In vitro analyses of the growth requirements of pro-T cells demonstrated the involvement of the IL-2 pathway in promoting their proliferation and differentiation into CD3+ CD4+ or CD8+ mature thymocytes. Moreover, during the IL-2-mediated maturation process rearrangements and expression of both alpha and beta chain TCR genes occurred, and resulted in the acquisition of alpha/beta as well as gamma/delta (either disulphide-linked or non-disulphide-linked) heterodimeric TCR among the pro-T cell progeny.


The value of preoperative planning for total hip arthroplasty.
To analyse the value and accuracy of preoperative planning for total hip replacement (THR) we digitised electronically and compared the hand-sketched preoperative plans with the pre- and postoperative radiographs of 100 consecutive primary THRs. The correct type of prosthesis was planned in 98%; the agreement between planned and actually used components was 92% on the femoral side and 90% on the acetabular side. The mean (+/- SD) absolute difference between the planned and actual position of the centre of rotation of the hip was 2.5 +/- 1.1 mm vertically and 4.4 +/- 2.1 mm horizontally. On average, the inclination of the acetabular component differed by 7 +/- 2 degrees and anteversion by 9 +/- 3 degrees from the preoperative plans. The mean postoperative leg-length difference was 0.3 +/- 0.1 cm clinically and 0.2 +/- 0.1 cm radiologically. More than 80% of intraoperative difficulties were anticipated. Preoperative planning is of significant value for the successful performance of THR.


A Randomised Open Label Comparative Clinical Trial on the Efficacy of Latanoprost and Timolol in Primary Open Angle Glaucoma.
Timolol, a beta blocker, is the most commonly prescribed first line therapy in the treatment of primary open angle glaucoma. Latanoprost, a prostaglandin analogue, is a novel drug in glaucoma therapy. Its efficacy has to be proved for it to be included under the first line therapy in the treatment of primary open angle glaucoma. To compare the efficacy of Latanoprost with that of Timolol in the treatment of primary open angle glaucoma (POAG). In this study the enrolled patients were randomly divided into two groups by block randomization. The sample size was determined to be 60 in each group. One group received 0.005% of Latanoprost once daily in the evening and the other group 0.5% of Timolol twice daily. The efficacy was measured in terms of intraocular pressure at scheduled follow up visits. At the start of the study, intraocular pressures of both groups were comparable. At the end point, reduction of intraocular pressure among Latanoprost group was significantly greater than that of Timolol group (9.72 vs 7.27, p = 0.002). Latanoprost was found to be superior to Timolol in reducing the intraocular pressure in treatment of patients with primary open angle glaucoma.


Synchronous exocytosis in Paramecium cells involves very rapid (less than or equal to 1 s), reversible dephosphorylation of a 65-kD phosphoprotein in exocytosis-competent strains.
Synchronous exocytosis in Paramecium cells involves the rapid (less than or equal to 1 s) dephosphorylation of a 65-kD phosphoprotein, which, after a lag phase of approximately 5 s, is reversed within approximately 20 s. Exocytosis inhibitors suppress this reaction; stimulatory and inhibitory effects are dose dependent. The dephosphorylation of the 65-kD phosphoprotein occurs only in exocytosis-competent strains, but not in mutant strains that cannot carry out membrane fusion, or that are devoid of secretory organelles or cannot transport them to the cell membrane. Since under all conditions analyzed the transient dephosphorylation of the 65-kD phosphoprotein strictly parallels the actual amount of exocytosed organelles, this process might be involved in exocytosis performance, perhaps in its initiation.


Midazolam compared with ketamine for invasive procedures.
The combination of ketamine and topical placebo cream was compared with the combination of midazolam and topical lidocaine-prilocaine cream (EMLA) in 13 children with leukaemia undergoing bone marrow punctures. This double-blind, randomized, crossover study showed that the children prefer midazolam and EMLA as sedation for invasive procedures and that some parents and the nursing staff have doubts because of the anxiety during the procedure and the physical restraint that often is necessary during midazolam and EMLA. Both methods cause several, more or less unpleasant, side effects.


Effectiveness of small road tunnels and fences in reducing amphibian roadkill and barrier effects at retrofitted roads in Sweden.
Schemes to reduce road impacts on amphibians have been implemented for decades in Europe, yet, several aspects on the effectiveness of such schemes remain poorly understood. Particularly in northern Europe, including Sweden, there is a lack of available information on road mitigation for amphibians, which is hampering implementation progress and cost-effectiveness analyses of mitigation options. Here, we present data derived from systematic counts of amphibians during spring migration at three previous hot-spots for amphibian roadkill in Sweden, where amphibian tunnels with guiding fences have been installed. We used the data in combination with a risk model to estimate the number of roadkills and successful crossings before vs. after mitigation and mitigated vs. adjacent non-mitigated road sections. In mitigated road sections, the estimated number of amphibians killed or at risk of being killed by car traffic decreased by 85-100% and the estimated number successfully crossing the road increased by 25-340%. Data, however, suggested fence-end effects that may moderate the reduction in roadkill. We discuss possible explanations for the observed differences between sites and construction types, and implications for amphibian conservation. We show how effectiveness estimates can be used for prioritizing amphibian passages along the existing road network. Finally, we emphasize the importance of careful monitoring of amphibian roadkill and successful crossings before and after amphibian passages are constructed.


The relative protein abundance of UGT1A alternative splice variants as a key determinant of glucuronidation activity in vitro.
Alternative splicing (AS) is one of the most significant components of the functional complexity of human UDP-glucuronosyltransferase enzymes (UGTs), particularly for the UGT1A gene, which represents one of the best examples of a drug-metabolizing gene regulated by AS. Shorter UGT1A isoforms [isoform 2 (i2)] are deficient in glucuronic acid transferase activity but function as negative regulators of enzyme activity through protein-protein interaction. Their abundance, relative to active UGT1A enzymes, is expected to be a determinant of the global transferase activity of cells and tissues. Here we tested whether i2-mediated inhibition increases with greater abundance of the i2 protein relative to the isoform 1 (i1) enzyme, using the extrahepatic UGT1A7 as a model and a series of 23 human embryonic kidney 293 clonal cell lines expressing variable contents of i1 and i2 proteins. Upon normalization for i1, a significant reduction of 7-ethyl-10-hydroxycamptothecin glucuronide formation was observed for i1+i2 clones (mean of 53%) compared with the reference i1 cell line. In these clones, the i2 protein content varied greatly (38-263% relative to i1) and revealed two groups: 17 clones with i2 < i1 (60% ± 3%) and 6 clones with i2 ≥ i1 (153% ± 24%). The inhibition induced by i2 was more substantial for clones displaying i2 ≥ i1 (74.5%; P = 0.001) compared with those with i2 < i1 (45.5%). Coimmunoprecipitation supports a more substantial i1-i2 complex formation when i2 exceeds i1. We conclude that the relative abundance of regulatory i2 proteins has the potential to drastically alter the local drug metabolism in the cells, particularly when i2 surpasses the protein content of i1.


Using discussion groups as a strategy for postgraduate implant dentistry students to reflect.
More than undergraduates, postgraduate students have the day-to-day clinical experience to reflect upon. Nevertheless, reflection in postgraduate dental education is less well studied. Hence, the purpose was to investigate the attitude towards reflection and the content of reflections in postgraduate implant dentistry education in the UK and Belgium. To investigate the attitude towards reflection, a questionnaire was administered to the 10 postgraduates at UCL Eastman Dental Institute (EDI) and 6 postgraduates at Ghent University (UGent). Additionally, students were invited to attend two reflective sessions (60-90 minutes). The sessions' audio recordings were transcribed and analysed using a thematic approach. In total, 16 postgraduate implant dentistry students participated. Although the majority reported prior experience with reflection, there was variation in the provided definitions of reflection. EDI students agreed with reflection being beneficial for professional development/clinical reasoning and were positive about discussing clinical experiences in groups, but were divided about individual/group reflections. Their UGent counterparts were more indecisive (=neutral), but were positive about discussing clinical experiences. Thematic analysis identified recurring themes as individual learning process, learning and clinical experiences, attitude towards implant dentistry and course programme. EDI postgraduates' reflections focussed on specific clinical situations, while UGent postgraduates' reflections described general considerations. Although students/professionals often report to reflect, it is not clear whether/how they actually reflect, due to the all-purpose word reflection has become. A strategy, using group discussions along with supervision/guidance in how to reflect, demonstrated to expand clinical reasoning into reflections about postgraduate students' clinical actions and professional growth.


Fine-needle aspiration cytology of hemangiopericytoma: A report of five cases.
Hemangiopericytoma (HPC) is a relatively rare neoplasm, accounting for approximately 2.5% of all soft tissue tumors. Its histopathology has been well documented but to the authors' knowledge reports regarding its fine-needle aspiration (FNA) cytology rarely are encountered. In the current study the authors report the cytologic findings in FNA specimens from nine confirmed cases of HPC and attempt to correlate the cytologic features with the biologic outcomes. FNA was performed with or without radiologic guidance. Corresponding sections of tissue were reviewed in conjunction with the cytologic preparations. Nine FNAs were performed in 5 patients (3 men and 2 women) with an age range of 38-77 years (mean, 56 years). Two lesions were primary soft tissue lesions arising in the lower extremities; seven were recurrent or metastatic lesions from bone (one lesion), kidney (one lesion), pelvic fossa (one lesion), lower extremities (two lesions), trunk (one lesion), and breast (one lesion). All aspirates were cellular and were comprised of single and tightly packed clusters of oval to spindle-shaped cells aggregated around branched capillaries. Basement membrane material was observed in 6 cases (67%). The nuclei were uniform and oval, with finely granular chromatin and inconspicuous nucleoli in all cases except one. No mitotic figures or areas of necrosis were identified. A correct diagnosis of HPC was made on one primary lesion and all recurrent or metastatic lesions. HPCs show a spindle cell pattern in cytologic preparations and must be distinguished from more common spindle cell lesions. The presence of branched capillaries and abundant basement membrane material supports a diagnosis of HPC. Immunohistochemistry and electron microscopy performed on FNA samples may be helpful in the differential diagnosis. FNA is a useful and accurate tool with which to confirm recurrent or metastatic HPC; however, prediction of the biologic behavior of HPC based on cytologic features is not feasible. Cancer (Cancer Cytopathol)


The human right to water and sanitation: a new perspective for public policies.
The recognition of the human right to water and sanitation (HRtWS) by the United Nations General Assembly and Human Rights Council in 2010 constituted a significant political measure whose direct consequences are still being assessed. Previous to this date, the HRtWS and its link to a healthy life and adequate standard of living had been recognised in diverse legal and judicial spheres worldwide, in some cases under the pressure of the initiatives of strong social movements. However, while the HRtWS is recognised by the UN State Members, it constitutes a concept in construction that has not been approached and interpreted in consensual ways by all concerned stakeholders. The present article presents a formal definition of this right with a base in human rights regulation. It attempts to dialogue with the different existing perspectives regarding the impact of its international recognition as a human right. It then elucidates the progressive development of the HRtWS in law and jurisprudence. Finally, it considers the urgency and challenge of monitoring the HRtWS and discusses important implications for public policies.


Perturbative Confinement in Thermal Yang-Mills Theories Induced by Imaginary Angular Velocity.
We perturbatively compute the Polyakov loop potential at high temperature with finite imaginary angular velocity. This imaginary rotation does not violate the causality, and the thermodynamic limit is well defined. We analytically show that the imaginary angular velocity induces the perturbatively confined phase and serves as a new probe to confinement physics. We discuss a possible phase diagram that exhibits adiabatic continuity from the perturbative confinement to the confined phase at low temperature. We also mention subtlety in the analytical continuation from imaginary to real angular velocity by imposing a causality bound.


The epidemiology of human brucellosis in a well defined urban population in Saudi Arabia.
A retrospective survey was undertaken to provide the first reported estimate of the incidence of human brucellosis in Saudi Arabia. The study population was unusually well defined and consisted of all individuals resident in the Riyadh and Al Kharj regions and registered for treatment in the Riyadh-Al Kharj Hospital Program. Cases satisfying predetermined case criteria were identified initially from a retrospective review of hospital laboratory records, and this was supported by a review of individual medical case-notes. Brucellosis was found to be much more common in Saudi nationals than expatriate nationals. Among Saudi nationals the study demonstrated a remarkable increase in brucellosis with increasing age, and a higher incidence amongst women than men in some age groups. This was felt to have been due either to an increased exposure to infected livestock, or to an increased susceptibility to the disease in women, and with increasing age. There was a seasonal fluctuation in the occurrence of brucellosis with the largest number of cases occurring in spring and summer.


HDAC inhibitor-based therapies and haematological malignancy.
Reversible acetylation mediated by histone deacetylase (HDAC) influences a broad repertoire of physiological processes, many of which are aberrantly controlled in tumour cells. Since HDAC inhibition prompts tumour cells to enter apoptosis, small-molecule HDAC inhibitors have been developed as a new class of mechanism-based anticancer agent, many of which have entered clinical trials. While the clinical picture is evolving and the precise utility of HDAC inhibitors remains to be determined, it is noteworthy that certain tumour types undergo a favourable response, in particular haematological malignancies. Vorinostat (suberoylanilide hydroxamic acid) has been approved for treating cutaneous T-cell lymphoma in patients with progressive, persistent or recurrent disease. Here, we discuss developments in our understanding of molecular events that underlie the anticancer effects of HDAC inhibitors and relate this information to the emerging clinical picture for the application of HDAC inhibitors in haematological malignancies.


[Accidents and injuries due to consumption of alcohol or drugs in patients treated at an emergency room].
The aims of the study were to describe the differences in alcohol consumption by sex, education and occupation and to understand the effects of the socio-demographic characteristics on alcohol consumption, in 120 emergency room patients. The results showed significant differences for sex (t=-3.570, p <.01) and education (t=2.636, p <.01) in alcohol consumption. In addition the factors; age, age alcohol consumption started, quantity of alcohol ingested, age marijuana consumption started, and hours lapsed between the consumption of marijuana and the accident (F(7, 116)=15.519, p <.00), were also significant on the consumption of alcohol with an explained variance of 40%.


Diagnostic utility of TP53 and cytokeratin 7 immunohistochemistry in idiopathic inflammatory bowel disease-associated neoplasia.
Long-standing inflammatory bowel disease is associated with increased risk of developing colorectal adenocarcinoma. Significant intra- and inter-observers' variability exists in histologic interpretation of dysplasia in surveillance biopsies. In this study, we evaluated the utility of a panel of immunohistochemical markers in diagnosing inflammatory bowel disease-associated neoplasia. We reviewed 39 colectomy specimens with inflammatory bowel disease-associated neoplasia. In these 39 cases, we identified 172 foci of interest (5 normal, 58 negative for dysplasia, 15 indefinite for dysplasia, 59 low-grade dysplasia, 18 high-grade dysplasia, and 17 invasive adenocarcinoma). They were subjected to immunohistochemistry for TP53 and CK7. Logistic regression was used to evaluate their association with the presence of dysplasia. Receiver operating characteristic curves were used to determine the optimal cutoffs and assess the diagnostic performance of TP53 and CK7. Both TP53 nuclear staining and CK7 immunoreactivity gradually increased in the progression of inflammatory bowel disease-associated neoplasia (P<0.0001). CK7 immunoreactivity increased along with the increase of inflammation severity (P=0.0002) as well as reactive changes (P=0.04) in the colonic mucosa. But TP53 nuclear staining was independent of either feature. When both TP53>8% and CK7>30% as identified from logistic regression and receiver operating characteristic curves were used to diagnose dysplasia, the specificity achieved as high as 95%. When either TP53>8% or CK7>30% was used to diagnose dysplasia, the sensitivity achieved was 82%. Our results suggested that a combination of CK7 and TP53 immunohistochemistry may be helpful in diagnosing inflammatory bowel disease-associated dysplasia in difficult cases.


[Comparison of six radionuclidic and non-radionuclidic methods for the assessment of glomerular filtration rate in patients with chronic renal failure].
The assessment of renal function in patients with chronic renal failure has a significant impact on both prognosis and treatment. We were unable to find a study, comparing six radionuclidic and non-radionuclidic methods as tested in this study on the same patients for the assessment of renal function in order to evaluate the relative significance of each method. In this study 82 patients were enrolled, 31 females with an age range 18-73 y (mean: 46 y) and 51 males with an age range 20-77 y (mean: 48 y). The level of renal function of these subjects ranged between normal, and mild to severe renal failure with serum creatinine levels: 2.7+/-2.2 mg/dl (mean+/-SD). The methods used for the glomerular filtration rate (GFR) were: (a) the clearance of inulin; (b) the technetium 99m labeled-diethyleno triamine pentacetic acid (99m)Tc-DTPA plasma disappearance curve; (c) the UV/P formula, not corrected for the residual urine volume in the bladder [DTPA(-)]; (d) the UV/P formula corrected for the residual urine volume in the bladder [DTPA(+)]; (e) plasma clearance of creatinine by the Cockcroft-Gault formula; and (f) plasma clearance of creatinine by using a 24-hour urine collection. In a subgroup of 13/82 patients, GFR was assessed by the radionuclidic and non-radionuclidic methods and compared against clearance of inulin, which was considered to be the gold standard. Moreover, we evaluated in our results the impact of age, gender, cause and stage of renal failure and the effect of the residual urine volume in the bladder. Fifteen of our patients were re-evaluated after 19-21 weeks. Spearman's correlation was used for statistical analysis; a two-sided P value < 0.05 was considered as statistically significant. Our results have shown that: the DTPA(+) method displayed the best correlation with the clearance of inulin (r=0.996) and was considered as the reference method in this study. The radionuclidic methods (99m)Tc-DTPA) plasma disappearance curve and DTPA(-) gave similar and comparable results with DTPA(+) (r=0.98, r=0.96), while the non-radionuclidic methods(plasma clearance of creatinine by using a 24-hour urine collection and plasma clearance of creatinine by the Cockcroft-Gault formula) tended to overestimate GFR respectively(r=0.91, r=0.79). Patient's age and gender had no impact on the calculated GFR values. With regards to the chronic renal failure cause, the above-mentioned tendencies were confirmed in primary and secondary glomerulonephritis, in diabetic nephropathy, and in hereditary renal diseases. On the contrary, in patients with renal disease of unknown cause, all methods -- isotopic and non-isotopic -- gave comparable results. The DTPA(-) method is simple to use and reliable, however, due to the fact that it does not consider the residual urine volume in the bladder, it seems to overestimate GFR in elderly men with prostate hypertrophy and increased residual urine volume in the bladder. The DTPA(+) method is reliable in a wide range of renal function levels, from mild to significant renal impairment. The radionuclidic methods DTPA(+), DTPA(-) and the (99m)Tc-DTPA plasma disappearance curves showed a very good reproducibility (r =0.97, r =0.96, r = 0.87) when were reperformed after 19-21 weeks, as compared to creatinine clearance with 24-hour urine collection (r=0.83). In conclusion, the radionuclidic methods in patients with chronic renal failure are reliable and reproducible, closely resembling those of inulin clearance. The among all radionuclidic methods, (99m)Tc-DTPA(+) shows the best results.


Synthesis and pharmacological characterization of a series of geometrically constrained 5-HT(2A/2C) receptor ligands.
In studies of the SAR of phenethylamine-type serotonin 5-HT(2A) receptor agonists, substituted conformationally constrained tetrahydronaphthofurans were designed to investigate the optimal conformation of the 2-aminoethyl moiety. These compounds were tested using in vitro assays for affinity at 5-HT(1A), 5-HT(2A), and 5-HT(2C) receptors. The benzofuran-containing analogues, 6a and 6b, had significantly higher affinity for the 5-HT receptors tested than did the benzodihydrofuran-containing compounds, 4a, 4b, 5a, and 5b. The most potent compound (8-bromo-6-methoxy-4,5-dihydro-3H-naphtho[1,8-bc]furan-5-yl)aminomethane, 6b, had K(i) values for displacement of [(125)I]-DOI from 5-HT(2A) and 5-HT(2C) cloned rat receptors of 2.6 and 1.1 nM, respectively. Despite their high affinity, the compounds of this naphthofuran series lacked high intrinsic activity at the 5-HT(2A) receptor as measured using the phosphoinositide hydrolysis assay. The most potent compound in vitro, 6b, was tested in the two-lever drug discrimination assay in rats trained to discriminate LSD from saline, and failed to substitute, a result typical for compounds with low intrinsic activity. Thus, although conformational constraint has led to high-affinity 5-HT(2A) ligands with partial agonist activity, all of the spatial and steric properties of the ligand necessary for full receptor activation have not yet been identified.


Detection of experimental cartilage damage with acoustic emissions technique: An in vitro equine study.
In horses, osteoarthritis (OA) mostly affects metacarpophalangeal and metatarsophalangeal (fetlock) joints. The current modalities used for diagnosis of equine limb disorders lack ability to detect early OA. Here, we propose a new alternative approach to assess experimental cartilage damage in fetlock joint using Acoustic Emissions (AE). To evaluate the potential of AE technique in diagnosing OA and see how AE signals changes with increasing severity of OA. An in vitro experimental study. A total of 16 distal limbs (8 forelimbs and 8 hindlimbs) from six Finn horses were collected from an abattoir and fitted in a custom-made frame allowing fetlock joint bending. Eight fetlock joints were opened, and cartilage surface was progressively damaged mechanically three times using sandpaper to mimic mild, moderate and severe OA. The remaining eight fetlock joints were opened and closed without any mechanical procedure, serving as controls. Before cartilage alteration, synovial fluid was aspirated, mixed with phosphate-buffered saline solution, and then reinjected before suturing for constant joint lubrication. For each simulated condition of OA severity, a force was applied to the frame and then released to mimic joint flexion and extension. AE signals were acquired using air microphones. A strong association was found between the joint condition and the power of AE signals analysed in 1.5-6 kHz range. The signal from both forelimb and hindlimb joints followed a similar pattern for increased cartilage damage. There were statistically significant differences between each joint condition progressively (generalised linear mixed model, P<0.001) in limbs with in vitro cartilage damage of varying severity while the control limbs did not show any changes. Small sample size using in vitro, mechanically induced cartilage damage. The AE technique presented here could differentiate the severity of fetlock joint cartilage damage. The consistent results for each simulated condition suggest there is potential for this method in the diagnosis of OA.


Chemically modified gelatin as biomaterial in the design of new nanomedicines.
The synthesis of new polymers has led to dramatic enhancements in the medical field. In particular, new chemical entities provided new prospects in tissue engineering, cellular therapy and drug delivery. However, significant efforts still need to be taken in consideration in order to achieve diverse clinical applications in these fields, which is challenging because of the lack of suitable materials with desired microstructure, permeability, degradation rates, products, and suitable mechanical properties. For these reasons some chemical strategies are focused in back to the nature approaches or, in other words, in improving the properties of natural polymers by chemical modifications. We report that by using a simple chemical modification technique we can obtain new biomaterials, specifically suitable for biomedical applications. Concretely, we describe the chemical modification of gelatin and the suitable characteristics of the modified protein to develop new nanomedicines. This protein was selected because of its enormous potential in biomedicine, which is currently limited due to the difficulty of its use without toxic chemical crosslinkers. The modification of the protein was based on the transformation of the carboxylic group into amido groups after their reaction with polyamines, leading to a positively charged biopolymer. To cationize the gelatin two polyamines where used: ethylenediamine and spermine, the latter being one of the endogenous polyamines which has a very positive influence over cells. This modification was monitored by physico-chemical techniques such as NMR, spectrophotometry and potentiometry. With the most promising modified gelatins we were able to develop nanoparticles using the ionotropic gelation technique. In order to determine the ability of these new nanosystems to associate bioactive molecules we selected a model plasmid DNA. The developed nanosystems were characterized corroborating their ability to associate the genetic material. In conclusion, we were able to obtain a semi-synthetic biomaterial with tunable physico-chemical properties, which can be used to develop new nanosystems with the ability to associate genetic material. We therefore propose that the gelatin, with its chemical modification, provide a unique biomaterial for the development of new nanomedicines.


[The reorganization of bimanual movements during formation of a lateralized motor food skill in rats].
After 48 h food deprivation adult Wistar rats were trained to obtain food from a narrow tube feeder using the forepaw under conditions of free choice of limb. At the initial stage of training animals use both paws: the grasping and extraction with one paw can be alternated with food grasping and extraction with another paw, and both paws can be alternately involved in movements preceding this grasping. Character of reorganization of bimanual movements was analyzed during training rats with different motor preference (right-handed and left-handed animals). It was shown that in the process of acquisition of both right- and left-hand skills, bimanual reactions in the anticipating attempts disappeared later than in the final successful movements. The disappearance of bimanual movements in the anticipating attempts is considered as an index of the maximum skill lateralization and acquisition of a novel lateralized movement coordination. The results suggest that left-handed rats more rapidly learn a novel movement coordination than right-handed animals.


Elevated serum IgE, oral corticosteroid dependence and IL-17/22 expression in highly neutrophilic asthma.
Information on the clinical traits associated with bronchial neutrophilia in asthma is scant, preventing its recognition and adequate treatment. We aimed to assess the clinical, functional and biological features of neutrophilic asthma and identify possible predictors of bronchial neutrophilia.The inflammatory phenotype of 70 mild-to-severe asthma patients was studied cross-sectionally based on the eosinophilic/neutrophilic counts in their bronchial lamina propria. Patients were classified as neutrophilic or non-neutrophilic. Neutrophilic asthma patients (neutrophil count cut-off: 47.17 neutrophils·mm-2; range: 47.17-198.11 neutrophils·mm-2; median: 94.34 neutrophils·mm-2) were further classified as high (≥94.34 neutrophils·mm-2) or intermediate (47.17- <94.34 neutrophils·mm-2). The effect of smoking ≥10 pack-years was also assessed.Neutrophilic asthma patients (n=38; 36 mixed eosinophilic/neutrophilic) had greater disease severity, functional residual capacity, inhaled corticosteroid (ICS) dose and exacerbations, and lower forced vital capacity (FVC) % pred and forced expiratory volume in 1 s (FEV1) reversibility than non-neutrophilic asthma patients (n=32; 28 eosinophilic and four paucigranulocytic). Neutrophilic asthma patients had similar eosinophil counts, increased bronchial CD8+, interleukin (IL)-17-F+ and IL-22+ cells, and decreased mast cells compared with non-neutrophilic asthma patients. FEV1 and FVC reversibility were independent predictors of bronchial neutrophilia in our cohort. High neutrophilic patients (n=21) had increased serum IgE levels, sensitivity to perennial allergens, exacerbation rate, oral corticosteroid dependence, and CD4+ and IL-17F+ cells in their bronchial mucosa. Excluding smokers revealed increased IL-17A+ and IL-22+ cells in highly neutrophilic patients.We provide new evidence linking the presence of high bronchial neutrophilia in asthma to an adaptive immune response associated with allergy (IgE) and IL-17/22 cytokine expression. High bronchial neutrophilia may discriminate a new endotype of asthma. Further research is warranted on the relationship between bronchoreversibility and bronchial neutrophilia.


Quantitative humoral profiling of the HIV-1 proteome in elite controllers and patients with very long-term efficient antiretroviral therapy.
A major challenge in evaluating the success of HIV eradication approaches is the need for accurate measurement of persistent HIV during effective antiretroviral therapy (ART). Previous studies have reported that the anti-HIV antibody assay "luciferase immuno-precipitation systems (LIPS)" can distinguish HIV-infected individuals harboring different sizes of the viral reservoirs. We performed antibody profiling of HIV-1 proteomes using LIPS in viremic progressors (n = 38), elite controllers (ECs; n = 19) and patients with fully suppressive long-term antiretroviral therapy (ART) (n = 19) (mean 17 years). IgG was quantified against six HIV-1 fusion proteins: p24, gp41, RT, Tat, integrase and protease. Lower antibody levels to all six-fusion proteins were observed in long-term ART patients compared to viremics (p < 0.05). In contrast ECs had lower antibody levels only against Tat and Integrase (p < 0.05). Principal component analysis and cluster-network analysis identified that 68% (13/19) of the long-term ART patients clustered together with 26% (5/19) ECs. The remaining ECs clustered together with the viremics indicating non-homogeneity among the ECs. The low anti-HIV levels in the long-term treated patients may indicate a restricted remaining viral replication. In contrast, the higher levels in ECs suggest a continuous viral expression with a limited concomitant release of extracellular virus.


A qualitative analysis of the tobacco control climate in the U.S. military.
Rates of tobacco use in the U.S. military have traditionally been higher than in the general U.S. population. While the military has experienced decreases in tobacco use over the past two decades, recent surveys suggest a trend of increased use. Given the negative impact of tobacco on both the readiness and the long-term health of military members, it is important to understand what factors may be related to the increased use rates. It has been suggested that there is a culture that supports tobacco use in the military. We examined perceptions about the climate of tobacco control among military installation Tobacco Control Managers and Service Policy Leaders from all four branches of the military (n = 52) using semistructured interviews. The primary strength of the military's tobacco control program, according to the participants, was mandating the provision of treatment services on every military installation. Any military member can receive both counseling and pharmacotherapy for tobacco. Opinions vary on the most promising new strategies for tobacco control. Many have pushed for a completely tobacco-free Department of Defense, including requiring troops to be tobacco-free and banning tobacco sales on military installations. However, a number of tobacco control experts within the military worry about unintended consequences of a complete ban. While several benefits of the current tobacco control program were identified, opportunities for improvement were identified at both the installation and service level.


Localization of human Cdc25C is regulated both by nuclear export and 14-3-3 protein binding.
Entry into mitosis requires activation of the Cdc2 protein kinase by the Cdc25C protein phosphatase. The interactions between Cdc2 and Cdc25C are negatively regulated throughout interphase and in response to G2 checkpoint activation. This is accomplished in part by maintaining the Cdc25 phosphatase in a phosphorylated form that binds 14-3-3 proteins. Here we report that 14-3-3 binding regulates the intracellular trafficking of Cdc25C. Although primarily cytoplasmic, Cdc25C accumulated in the nuclei of leptomycin B (LMB)-treated cells, indicating that Cdc25C is actively exported out of the nucleus. A mutant of Cdc25C that is unable to bind 14-3-3 was partially nuclear in the absence of LMB and its nuclear accumulation was greatly enhanced by LMB-treatment. A nuclear export signal (NES) was identified within the amino terminus of Cdc25C. Although mutation of the NES did not effect 14-3-3 binding, it did cause nuclear accumulation of Cdc25C. These results demonstrate that 14-3-3 binding is dispensable for the nuclear export of Cdc25C. However, complete nuclear accumulation of Cdc25C required loss of both NES function and 14-3-3 binding and this was accomplished both pharmacologically and by mutation. These findings suggest that the nuclear export of Cdc25C is mediated by an intrinsic NES and that 14-3-3 binding negatively regulates nuclear import.


Direct intracranial sagittal and coronal CT scanning: anatomy and pathology.
The application of whole-body scanners with a wide aperture cone to neuroradiology permits examination of the head in the sagittal plane. This method yields better definition of anatomic structures such as the inner and outer supra- and infratentorial cerebrospinal fluid spaces, the major vessels, and all structures of the posterior fossa close to the midline with negligible artifacts. By mono-, bi-, or triplanar approaches, intracranial pathology can be demonstrated exactly with respect to the major anatomic landmarks, without the disadvantages of multiplanar reconstructed views. In combination with an altered positioning for coronal scanning, optimal biplane evaluation of the sellar region is possible. Additional cisternal enhancement studies in variants of empty sella and brainstem tumors may not always be necessary. The sagittal section, like the coronal, can be placed lateral to metallic clips for early detection of tumor recurrence. Limitations are discomfort in positioning and a degradation of image quality caused by metal amalgam fillings.


GEJ cancers: gastric or esophageal tumors? searching for the answer according to molecular identity.
The 7th edition of Union for International Cancer Control (UICC) staging system moved gastroesophageal junction (GEJ) cancers from gastric to esophageal group. Since clinical management is strongly influenced by this staging system, we looked at molecular fingerprints of GEJ tumors and compared to gastric and esophageal profiles. We aimed at elucidating whether GEJ cancers cluster with gastric or esophageal groups according to mRNA and microRNA expression pattern, since this might represent tumor identity. The clinical and expression data were downloaded from The Cancer Genome Atlas (TCGA) with 395 stomach, 184 esophagus and 521 colon samples for mRNA analyses and 392 stomach, 175 esophagus and 459 colon samples for microRNA comparisons. Both Principal Component Analysis (PCA) and Heat Map plots were performed in R platform, using Log2 transformation of RPKM normalized data. Differential Expression Analysis was also performed in R, using RAW data and the DESeq2 package. The mRNAs and microRNAs were tagged as differentially expressed if they met the following criteria: i) FDR adjusted p-value < 0.05; and ii) |Log2 (fold-change)| > 2. Esophagus squamous cell carcinoma (ESCC) clustered apart of the others tumors, while adenocarcinomas (AC) clustered all together according to both mRNAs and microRNAs expression patterns. The HMs of the differentially expressed mRNAs and microRNAs also demonstrated that ESCC belongs to a different group, while AC molecular signature of esophagus looks like AC of the cardia and non cardia regions. Even distal gastric cancers are quite similar to AC of the lower esophagus, demonstrating that esophagus AC relies much closer to gastric cancers than to esophagus cancers. By using robust molecular fingerprints, it was strongly demonstrated that GEJ tumors looks more like gastric cancers than esophageal cancers, despite of tumor heterogeneity.


Comparison between constant and decreasing rest intervals: influence on maximal strength and hypertrophy.
Most resistance training programs use constant rest period lengths between sets and exercises, but some programs use decreasing rest period lengths as training progresses. The aim of this study was to compare the effect on strength and hypertrophy of 8 weeks of resistance training using constant rest intervals (CIs) and decreasing rest intervals (DIs) between sets and exercises. Twenty young men recreationally trained in strength training were randomly assigned to either a CI or DI training group. During the first 2 weeks of training, 3 sets of 10-12 repetition maximum (RM) with 2-minute rest intervals between sets and exercises were performed by both groups. During the next 6 weeks of training, the CI group trained using 2 minutes between sets and exercises (4 sets of 8-10RM), and the DI group trained with DIs (2 minutes decreasing to 30 seconds) as the 6 weeks of training progressed (4 sets of 8-10RM). Total training volume of the bench press and squat were significantly lower for the DI compared to the CI group (bench press 9.4%, squat 13.9%) and weekly training volume of these same exercises was lower in the DI group from weeks 6 to 8 of training. Strength (1RM) in the bench press and squat, knee extensor and flexor isokinetic measures of peak torque, and muscle cross-sectional area (CSA) using magnetic resonance imaging were assessed pretraining and posttraining. No significant differences (p < or = 0.05) were shown between the CI and DI training protocols for CSA (arm 13.8 vs. 14.5%, thigh 16.6 vs. 16.3%), 1RM (bench press 28 vs. 37%, squat 34 vs. 34%), and isokinetic peak torque. In conclusion, the results indicate that a training protocol with DI is just as effective as a CI protocol over short training periods (6 weeks) for increasing maximal strength and muscle CSA; thus, either type of program can be used over a short training period to cause strength and hypertrophy.


Mutations That Alter the Bacterial Cell Envelope Increase Lipid Production.
Lipids from microbes offer a promising source of renewable alternatives to petroleum-derived compounds. In particular, oleaginous microbes are of interest because they accumulate a large fraction of their biomass as lipids. In this study, we analyzed genetic changes that alter lipid accumulation in Rhodobacter sphaeroides By screening an R. sphaeroides Tn5 mutant library for insertions that increased fatty acid content, we identified 10 high-lipid (HL) mutants for further characterization. These HL mutants exhibited increased sensitivity to drugs that target the bacterial cell envelope and changes in shape, and some had the ability to secrete lipids, with two HL mutants accumulating ~60% of their total lipids extracellularly. When one of the highest-lipid-secreting strains was grown in a fed-batch bioreactor, its lipid content was comparable to that of oleaginous microbes, with the majority of the lipids secreted into the medium. Based on the properties of these HL mutants, we conclude that alterations of the cell envelope are a previously unreported approach to increase microbial lipid production. We also propose that this approach may be combined with knowledge about biosynthetic pathways, in this or other microbes, to increase production of lipids and other chemicals.IMPORTANCE This paper reports on experiments to understand how to increase microbial lipid production. Microbial lipids are often cited as one renewable replacement for petroleum-based fuels and chemicals, but strategies to increase the yield of these compounds are needed to achieve this goal. While lipid biosynthesis is often well understood, increasing yields of these compounds to industrially relevant levels is a challenge, especially since genetic, synthetic biology, or engineering approaches are not feasible in many microbes. We show that altering the bacterial cell envelope can be used to increase microbial lipid production. We also find that the utility of some of these alterations can be enhanced by growing cells in bioreactor configurations that can be used industrially. We propose that our findings can inform current and future efforts to increase production of microbial lipids, other fuels, or chemicals that are currently derived from petroleum.


Proof of physical exchange of genes on the chromosomes.
Seventy-five years ago, a convincing demonstration that the genes were physically aligned along the chromosome was lacking. Harriet Creighton (1909-2004) and Barbara McClintock (1902-1992) [Creighton, H. B. & McClintock, B. (1931) Proc. Natl. Acad. Sci. USA 17, 492-497] showed by an elegantly simple experiment in 1931 that exchange between genes was accompanied by exchange of cytological, i.e., physical, parts of chromosomes. The work has been acclaimed as one of the great experiments in biology. Creighton's doctoral dissertation under McClintock's mentorship provided the basis for the landmark paper, which was unique in merging cytological with genetic data. A companion paper by McClintock, printed and bound back-to-back with the joint paper, set the essential stage with data on the cytological and genetic features that Creighton applied. Following directly from this work, and leading to today's recognition that the genome is a graspable entity, was the knowledge that the genes could be studied as components of a linear structure, the chromosome. Here, we review the data surrounding the Creighton and McClintock paper and provide a perspective on the significance of their findings.


Plasmon-induced magneto-optical activity in nanosized gold disks.
In this Letter we show that nanostructures made out of pure noble metals can exhibit measurable magneto-optic activity at low magnetic fields. This phenomenon occurs when the localized surface plasmon resonance of the nanostructure is excited in the presence of a static magnetic field parallel to the propagation of incident light. The large magneto-optical response observed comes from an increase of the magnetic Lorentz force induced by the large collective movement of the conduction electrons in the nanostructures when the resonance is excited.


Moderator Effect of Transplant Waiting Time on the Relationship Between Hopelessness and Death Anxiety in Patients Waiting for Organ Transplant.
The study aimed to examine the moderator effect of organ transplant waiting time on hopelessness and death anxiety. The study was conducted in a descriptive and correlational design with 378 patients on the transplant waiting list (Agust 2021- March 2022). Multiple linear regression and PROCESS macro-Model 1 were used in the analyses. In this study, the STROBE checklist was followed. According to the results of the regression analysis, waiting for a transplant for 6-10 years reduced death anxiety by 9.38 times and waiting for a transplant for 16-20 years increased death anxiety by 31.3 times. The predictors in the regression analysis explained 33% of the model. The moderator effect constituted 6.4% of the explained part of the model, which was 25.4%; the R2 change was 3.4% and significant. We found that the longer the waiting period for organ transplant recipients, the higher the hopelessness and death anxiety.


Update on methodologies available for ciguatoxin determination: perspectives to confront the onset of ciguatera fish poisoning in Europe.
Ciguatera fish poisoning (CFP) occurs mainly when humans ingest finfish contaminated with ciguatoxins (CTXs). The complexity and variability of such toxins have made it difficult to develop reliable methods to routinely monitor CFP with specificity and sensitivity. This review aims to describe the methodologies available for CTX detection, including those based on the toxicological, biochemical, chemical, and pharmaceutical properties of CTXs. Selecting any of these methodological approaches for routine monitoring of ciguatera may be dependent upon the applicability of the method. However, identifying a reference validation method for CTXs is a critical and urgent issue, and is dependent upon the availability of certified CTX standards and the coordinated action of laboratories. Reports of CFP cases in European hospitals have been described in several countries, and are mostly due to travel to CFP endemic areas. Additionally, the recent detection of the CTX-producing tropical genus Gambierdiscus in the eastern Atlantic Ocean of the northern hemisphere and in the Mediterranean Sea, as well as the confirmation of CFP in the Canary Islands and possibly in Madeira, constitute other reasons to study the onset of CFP in Europe [1]. The question of the possible contribution of climate change to the distribution of toxin-producing microalgae and ciguateric fish is raised. The impact of ciguatera onset on European Union (EU) policies will be discussed with respect to EU regulations on marine toxins in seafood. Critical analysis and availability of methodologies for CTX determination is required for a rapid response to suspected CFP cases and to conduct sound CFP risk analysis.


Liver transplant patients have a risk of progression similar to that of sporadic patients with branch duct intraductal papillary mucinous neoplasms.
Intraductal papillary mucinous neoplasms (IPMNs) have malignant potential and can progress from low- to high-grade dysplasia to invasive adenocarcinoma. The management of patients with IPMNs is dependent on their risk of malignant progression, with surgical resection recommended for patients with branch-duct IPMN (BD-IPMN) who develop high-risk features. There is increasing evidence that liver transplant (LT) patients are at increased risk of extrahepatic malignancy. However, there are few data regarding the risk of progression of BD-IPMNs in LT recipients. The aim of this study was to determine whether LT recipients with BD-IPMNs are at higher risk of developing high-risk features than patients with BD-IPMNs who did not receive a transplant. Consecutive patients who underwent an LT with BD-IPMNs were included. Patients with BD-IPMNs with no history of immunosuppression were used as controls. Progression of the BD-IPMNs was defined as development of a high-risk feature (jaundice, dilated main pancreatic duct, mural nodule, cytology suspicious or diagnostic for malignancy, cyst diameter ≥3 cm). Twenty-three LT patients with BD-IPMN were compared with 274 control patients. The median length of follow-up was 53.7 and 24.0 months in LT and control groups, respectively. Four (17.4%) LT patients and 45 (16.4%) controls developed high-risk features (P = 0.99). In multivariate analysis, progression of BD-IPMNs was associated with age at diagnosis but not with LT. There was no statistically significant difference in the risk of developing high-risk features between the LT and the control groups.


Hyaluronic Acid-Based Injective Medical Devices: In Vitro Characterization of Novel Formulations Containing Biofermentative Unsulfated Chondroitin or Extractive Sulfated One with Cyclodextrins.
Currently, chondroitin sulfate (CS) and hyaluronic acid (HA) pharma-grade forms are used for osteoarthritis (OA) management, CS as an oral formulations component, and HA as intra-articular injective medical devices. Recently, unsulfated chondroitin, obtained through biofermentative (BC) manufacturing, has been proposed for thermally stabilized injective preparation with HA. This study aimed to highlight the specific properties of two commercial injective medical devices, one based on HA/BC complexes and the other containing HA, extractive CS, and cyclodextrins, in order to provide valuable information for joint disease treatments. Their biophysical and biomechanical features were assayed; in addition, biological tests were performed on human pathological chondrocytes. Rheological measurements displayed similar behavior, with a slightly higher G' for HA/BC, which also proved superior stability to the hyaluronidase attack. Both samples reduced the expression of specific OA-related biomarkers such as NF-kB, interleukin 6 (IL-6), and metalloprotease-13 (MMP-13). Moreover, HA/BC better ensured chondrocyte phenotype maintenance by up-regulating collagen type 2A1 (COLII) and aggrecan (AGN). Notwithstanding, the similarity of biomolecule components, the manufacturing process, raw materials characteristics, and specific concentration resulted in affecting the biomechanical and, more interestingly, the biochemical properties, suggesting potential better performances of HA/BC in joint disease treatment.


Food Environments Within and Outside of Schools Play a Critical Role in Curtailing the Rise in Obesity among School-Aged Children over Time.
Sound evidence for effective community-based strategies is needed to curtail upward trends in childhood obesity in the United States (US). The aim of the study was to assess the association between school and community food environments and the prevalence of obesity over time. Data were collected from K-12 schools in 4 low-income New Jersey cities in the US. School-level obesity prevalence, calculated from nurse-measured heights and weights at 4 time points, was used as the outcome variable. Data on the school food environment (SFE) measured the healthfulness of school lunch and competitive food offerings annually. The community food environment (CFE), i.e., the number of different types of food outlets within 400 m of schools, was also captured annually. The count and presence of food outlets likely to be frequented by students were calculated. Exposure to composite environment profiles both within schools and in communities around schools was assessed using latent class analysis. Data from 106 schools were analyzed using multilevel linear regression. The prevalence of obesity increased from 25% to 29% over the course of the study. Obesity rates were higher in schools that had nearby access to a greater number of limited-service restaurants and lower in schools with access to small grocery stores and upgraded convenience stores participating in initiatives to improve healthful offerings. Interaction analysis showed that schools that offered unhealthier, competitive foods experienced a faster increase in obesity rates over time. Examining composite food environment exposures, schools with unhealthy SFEs and high-density CFEs experienced a steeper time trend (β = 0.018, P < 0.001) in obesity prevalence compared to schools exposed to healthy SFE and low-density CFEs. Food environments within and outside of schools are associated with differential obesity trajectories over time and can play an important role in curtailing the rising trends in childhood obesity.


Coherent broadband light generation with a double-path configuration.
We generate broadband light by focusing two femtosecond pulses into a Raman-active crystal. By reflecting Raman sideband beams together with the two driving beams back to the same crystal (with a slight spatial offset), we generate sidebands covering a broader spectral range, compared to a single pass. In this novel double-path configuration, multiple Raman sideband beams interact with each other since the phase-matching condition is automatically fulfilled. This scheme enables an enhanced cascaded coherent anti-Stokes scattering process and also doubles the interaction length, thus it allows one to use relatively weak energy pump pulses and thereby avoid optical damage.


Comparative study of the quality of life between arthrodesis and total arthroplasty substitution of the ankle.
Our goal was to compare the health status of patients with primary and secondary arthrosis of the ankle before and after arthrodesis or total substitution arthroplasty, and to determine the improvement in quality of life and whether there is any difference between these techniques. A prospective comparative study of clinical-functional evaluation was performed using the American Orthopaedic Foot & Ankle Society (AOFAS) scale and quality of life with the short form (SF)-36 questionnaire in patients who underwent arthrodesis (16 cases) or total substitution arthroplasty of the ankle (14 cases) after 2 years (mean, 25.2 months) of follow-up after surgery, in comparison with the baseline preoperative status. In this series of comparable patients, both techniques showed a statistically significant improvement with regard to the clinical evaluation and quality of life after 2 years of follow-up; the arthrodesis group increased from mean AOFAS values of 37.12 to 45.62 (P = .055) and mean SF-36 values of 32.96 to 46.25 (P = .008), whereas in the arthroplasty group the mean values of AOFAS increased from 33 to 62 (P = .024) and SF-36 from 33.62 to 59.84 (P = .001). Nevertheless, in all cases the improvement was statistically greater in patients who underwent arthroplasty than in those who underwent arthrodesis (P = .048 for AOFAS, and P = .026 for SF-36). In conclusion, arthrodesis and arthroplasty represent good options in the surgical treatment of ankle arthrosis, providing both a significant improvement in function and in the health perception and quality of life of the patient. New-generation total ankle substitution arthroplasty provides an improvement in the quality of life and perception of general health of the patient with arthrosis of this joint, when this technique is compared with surgical fusion.


Prenatal dexamethasone use for the prevention of virilization in pregnancies at risk for classical congenital adrenal hyperplasia because of 21-hydroxylase (CYP21A2) deficiency: a systematic review and meta-analyses.
Prenatal treatment with dexamethasone to prevent virilization in pregnancies at risk for classical congenital adrenal hyperplasia (CAH) remains controversial. To conduct a systematic review and meta-analyses of studies that evaluated the effects of dexamethasone administration during pregnancies at risk for classical CAH because of 21-hydroxylase deficiency (CYP21A2). We searched MEDLINE, EMBASE, and Cochrane CENTRAL from inception through August 2009. Review of reference lists and contact with CAH experts further identified candidate studies. Reviewers working independently and in duplicate determined trial eligibility. Eligible studies reported the effects on either foetal or maternal outcomes of dexamethasone administered during pregnancy compared to a control group that did not receive any treatment. Reviewers working independently and in duplicate determined the methodological quality of studies and collected data on patient characteristics, interventions, and outcomes. We identified only four eligible observational studies (325 pregnancies treated with dexamethasone). The methodological quality of the included studies was overall low. Meta-analysis demonstrates a reduction in foetus virilization measured by Prader score in female foetuses treated with dexamethasone initiated early during pregnancy (weighted mean difference, -2.33, 95% CI, -3.38, -1.27). No deleterious effects of dexamethasone on stillbirths, spontaneous abortions, foetal malformations, neuropsychological or developmental outcomes were found although these data are quite sparse. There was increased oedema and striae in the mothers treated with dexamethasone. There were no data on long-term follow-up of physical and metabolic outcomes in children exposed to dexamethasone. The observational nature of the available evidence and the overall small sample size of the whole body of the literature significantly weaken inferences about the benefits and harms of dexamethasone in this setting. Dexamethasone seems to be associated with reduction in foetus virilization without significant maternal or foetal adverse effects. However, this review underscores the current uncertainty and further investigation is clearly needed. The decision about initiating treatment should be based on patients' values and preferences and requires fully informed and consenting parents.


Selective chemosensor for copper ions based on fluorescence quenching of a Schiff-base fluorophore.
A Schiff base-based fluorescent chemosensor has been studied for divalent copper detection. The formation of 2-hydroxybenzaldehyde benzoylhydrazone-Cu(2+) complex induced a fluorescence quenching of this compound in a medium of water/ethanol (53% v/v) and 0.05 M phosphate buffer (pH 7.0). The continuous variations and mole-ratio plots of absorbance suggested a complex formation with a 1:1 metal-ligand stoichiometry. The conditional stability constant for the complex was evaluated to be 6 x 10(6) M(-1). A modified Stern-Volmer relationship was employed to obtain a linear calibration plot, obtaining a dynamic working range up to 157.4 microM. The detection limit of this system was found to be 5.6 microM and the relative standard deviation for five measurements of 78.7 microM concentration was 5.2%. This fluorescent chemosensor also showed a high selectivity for copper ions over other metal ions, such as Al(3+), Ca(2+), Cd(2+), Fe(2+), K(+), Mg(2+), Na(+), Pb(2+), or Zn(2+). The results of this investigation show a simple, rapid, low-cost, and selective method that can operate in neutral solutions and is useful for biological and environmental applications.


Potential Changes in Greenhouse Gas Emissions from Refrigerated Supply Chain Introduction in a Developing Food System.
Refrigeration transforms developing food systems, changing the dynamics of production and consumption. This study models the introduction of an integrated refrigerated supply chain, or "cold chain," into sub-Saharan Africa and estimates changes in preretail greenhouse gas (GHG) emissions if the cold chain develops similarly to North America or Europe. Refrigeration presents an important and understudied trade-off: the ability to reduce food losses and their associated environmental impacts, but increasing energy use and creating GHG emissions. It is estimated that postharvest emissions added from cold chain operation are larger than food loss emissions avoided, by 10% in the North American scenario and 2% in the European scenario. The cold chain also enables changes in agricultural production and diets. Connected agricultural production changes decrease emissions, while dietary shifts facilitated by refrigeration may increase emissions. These system-wide changes brought about by the cold chain may increase the embodied emissions of food supplied to retail by 10% or decrease them by 15%, depending on the scenario.


NF45 dimerizes with NF90, Zfr and SPNR via a conserved domain that has a nucleotidyltransferase fold.
Nuclear factors NF90 and NF45 form a complex involved in a variety of cellular processes and are thought to affect gene expression both at the transcriptional and translational level. In addition, this complex affects the replication of several viruses through direct interactions with viral RNA. NF90 and NF45 dimerize through their common 'DZF' domain (domain associated with zinc fingers). NF90 has additional double-stranded RNA-binding domains that likely mediate its association with target RNAs. We present the crystal structure of the NF90/NF45 dimerization complex at 1.9-Å resolution. The DZF domain shows structural similarity to the template-free nucleotidyltransferase family of RNA modifying enzymes. However, both NF90 and NF45 have lost critical catalytic residues during evolution and are therefore not functional enzymes. Residues on NF90 that make up its interface with NF45 are conserved in two related proteins, spermatid perinuclear RNA-binding protein (SPNR) and zinc-finger RNA-binding protein (Zfr). Using a co-immunoprecipitation assay and site-specific mutants, we demonstrate that NF45 is also able to recognize SPNR and Zfr through the same binding interface, revealing that NF45 is able to form a variety of cellular complexes with other DZF-domain proteins.


Intravenous immunoglobulin and mitoxantrone stop the progression of secondary progressive multiple sclerosis in a patient with interferon intolerance.
A 36 year-old female patient with secondary progressive multiple sclerosis accompanied by neuropsychiatric depression and history of intolerance to beta-interferon was treated with mitoxantrone (MX) and intravenous immunoglobulin (IVIG) for 2 years. Both clinical response and magnetic resonance imaging were performed at the end. With a combination of MX and IVIG long-term treatment, her disabilities improved as measured by the Expanded Disability Status Scale (EDSS). The combination therapy was well-tolerated. It represents an alternative to treat patients who do not respond well to cytostatics alone, or in those in whom intolerance to interferons may also occur. Immunomodulation with intravenous immunoglobulin stopped the progression of the disease and avoided subsequent exacerbations during 24 months. The role of high doses of immunoglobulins in the treatment of patients with secondary progressive MS deserves clinical trials to evaluate the stopping of progression of the disease in comparison to remissions induced by cytostatics, interferons and steroids.


The Pattern Glare Test: a review and determination of normative values.
Pattern glare is characterised by symptoms of visual perceptual distortions and visual stress on viewing striped patterns. People with migraine or Meares-Irlen syndrome (visual stress) are especially prone to pattern glare. The literature on pattern glare is reviewed, and the goal of this study was to develop clinical norms for the Wilkins and Evans Pattern Glare Test. This comprises three test plates of square wave patterns of spatial frequency 0.5, 3 and 12 cycles per degree (cpd). Patients are shown the 0.5 cpd grating and the number of distortions that are reported in response to a list of questions is recorded. This is repeated for the other patterns. People who are prone to pattern glare experience visual perceptual distortions on viewing the 3 cpd grating, and pattern glare can be quantified as either the sum of distortions reported with the 3 cpd pattern or as the difference between the number of distortions with the 3 and 12 cpd gratings, the '3-12 cpd difference'. In study 1, 100 patients consulting an optometrist performed the Pattern Glare Test and the 95th percentile of responses was calculated as the limit of the normal range. The normal range for the number of distortions was found to be <4 on the 3 cpd grating and <2 for the 3-12 cpd difference. Pattern glare was similar in both genders but decreased with age. In study 2, 30 additional participants were given the test in the reverse of the usual testing order and were compared with a sub-group from study 1, matched for age and gender. Participants experienced more distortions with the 12 cpd grating if it was presented after the 3 cpd grating. However, the order did not influence the two key measures of pattern glare. In study 3, 30 further participants who reported a medical diagnosis of migraine were compared with a sub-group of the participants in study 1 who did not report migraine or frequent headaches, matched for age and gender. The migraine group reported more symptoms on viewing all gratings, particularly the 3 cpd grating. The only variable to be significantly different between the groups was the 3-12 cpd difference. In conclusion, people have an abnormal degree of pattern glare if they have a Pattern Glare Test score of >3 on the 3 cpd grating or a score of >1 on the 3-12 cpd difference. The literature suggests that these people are likely to have visual stress in everyday life and may therefore benefit from interventions designed to alleviate visual stress, such as precision tinted lenses.


Reflective multilayer coatings for the far uv region.
Progress in the field of reflective multilayer coatings for the wavelength region between 50 A and 2000 A is reviewed. All the coatings contain absorbing materials, absorption losses are minimized by positioning strongly absorbing materials into the nodes of the standing wave inside the coating. Above lambda = 1200 A, ideal coatings with a reflectivity approaching 100% are theoretically possible; the theoretical predictions have been confirmed for coatings up to six layers at wavelengths around 2000 A. Below lambda = 1000 A, no absorption-free material is available that can be used as a spacer layer to cover the antinodes of the standing wave field. This limits the theoretically obtainable reflectivity. However, even at the shortest wavelength a reflectivity of 30% is still possible. Experimental results have been obtained for wavelengths between 100 A and 200 A for coatings up to nine layers. Discrepancies between experiment and theory can be explained as due to insufficient knowledge of the optical constants of the films used. Extensive future work on the optical constants of materials and their dependence on film thickness and deposition conditions is required for further improvement.


Smart adaptive optic systems using spatial light modulators.
Many factors contribute to the aberrations induced in an optical system. Atmospheric turbulence between the object and the imaging system, physical or thermal perturbations in optical elements degrade the system's point spread function, and misaligned optics are the primary sources of aberrations that affect image quality. The design of a nonconventional real-time adaptive optic system using a micro-mirror device for wavefront correction is presented. The unconventional compensated imaging system presented offers advantages in speed, cost, power consumption, and weight. A pulsed-coupled neural network is used to as a preprocessor to enhance the performance of the wavefront sensor for low-light applications. Modeling results that characterize the system performance are presented.


Fisher: a program for the detection of H/ACA snoRNAs using MFE secondary structure prediction and comparative genomics - assessment and update.
The H/ACA family of small nucleolar RNAs (snoRNAs) plays a central role in guiding the pseudouridylation of ribosomal RNA (rRNA). In an effort to systematically identify the complete set of rRNA-modifying H/ACA snoRNAs from the genome sequence of the budding yeast, Saccharomyces cerevisiae, we developed a program - Fisher - and previously presented several candidate snoRNAs based on our analysis 1. In this report, we provide a brief update of this work, which was aborted after the publication of experimentally-identified snoRNAs 2 identical to candidates we had identified bioinformatically using Fisher. Our motivation for revisiting this work is to report on the status of the candidate snoRNAs described in 1, and secondly, to report that a modified version of Fisher together with the available multiple yeast genome sequences was able to correctly identify several H/ACA snoRNAs for modification sites not identified by the snoGPS program 3. While we are no longer developing Fisher, we briefly consider the merits of the Fisher algorithm relative to snoGPS, which may be of use for workers considering pursuing a similar search strategy for the identification of small RNAs. The modified source code for Fisher is made available as supplementary material. Our results confirm the validity of using minimum free energy (MFE) secondary structure prediction to guide comparative genomic screening for RNA families with few sequence constraints.


The Effects of Lavender Essential Oil on Wound Healing: A Review of the Current Evidence.
Background: The commercialization of essential oils has expanded their presence in the United States, and emerging studies demonstrate that they may have a place in Western medicine. One oil with a significant body of evidence is lavender essential oil, which may have benefits in wound healing. Objectives: This review aims to present the scientific literature on therapeutic lavender essential oil with the goal of expanding the current repertoire of cost-effective wound healing options available to physicians and patients. Methods: A review was conducted according to PRISMA guidelines in PubMed, Cochrane Library, and Embase from June 2018 through March 2019 to identify articles related to lavender essential oil in the context of wound healing. Results: This search yielded 36 unique studies, 20 of which remained after screening. This review utilizes human clinical trials (n = 7), animal trials (n = 5), in vitro studies (n = 2), and previously conducted reviews (n = 6). Overall, these studies demonstrated a faster rate of wound healing, increased expression of collagen, and enhanced activity of proteins involved in the tissue remodeling process in wounds treated with lavender essential oil. Conclusions: The current body of literature suggests a potential therapeutic benefit of lavender essential oil in wound healing. However, standardization of the chemical composition and additional high-quality human clinical trials are needed to further evaluate the safety and efficacy of lavender essential oil in clinical practice.


Quality of early care and childhood trauma: a prospective study of developmental pathways to dissociation.
Kihlstrom (2005) has recently called attention to the need for prospective longitudinal studies of dissociation. The present study assesses quality of early care and childhood trauma as predictors of dissociation in a sample of 56 low-income young adults followed from infancy to age 19. Dissociation was assessed with the Dissociative Experiences Scale; quality of early care was assessed by observer ratings of mother-infant interaction at home and in the laboratory; and childhood trauma was indexed by state-documented maltreatment, self-report, and interviewer ratings of participants' narratives. Regression analysis indicated that dissociation in young adulthood was significantly predicted by observed lack of parental responsiveness in infancy, while childhood verbal abuse was the only type of trauma that added to the prediction of dissociation. Implications are discussed in the context of previous prospective work also pointing to the important contribution of parental emotional unresponsiveness in the development of dissociation.


A community-based trial of a psychosocial eHealth intervention for parents of children with cancer.
The Electronic Surviving Cancer Competently Intervention Program (eSCCIP), a psychosocial eHealth intervention for parents and caregivers of children with cancer (parents), was delivered in a community-based psychosocial oncology center. Primary endpoints were intervention acceptability, feasibility, and accessibility, with a secondary exploratory focus on psychosocial outcomes. Oncology therapists in a psychosocial oncology center were trained in eSCCIP delivery. Participants were eligible for participation if they were the primary caregiver of a child with cancer between the ages 0 and 17, could read and write in English, and had reliable internet access to complete eSCCIP. Surveys were administered electronically at baseline and post intervention to evaluate study endpoints. Effect sizes (Cohen's d) were computed for exploratory psychosocial outcomes. Nineteen parents completed the intervention. Parents rated eSCCIP as highly acceptable, feasible, and accessible. A large clinical effect was detected for acute distress (d = 0.79). Moderate clinical effects were reported for overall posttraumatic stress disorder (PTSD) symptoms (d = 0.37), negative mood/cognitions (d = 0.59), and symptoms of anxiety (d = 0.48). Results indicate that eSCCIP is an acceptable, feasible, and accessible psychosocial intervention for parents. Exploratory analyses suggest that participation in eSCCIP may contribute to decreases in acute distress, symptoms of anxiety, and symptoms of PTSD.


Transcriptional activation of human LIM-HOX gene, hLH-2, in chronic myelogenous leukemia is due to a cis-acting effect of Bcr-Abl.
DNA methylation plays an important role in gene regulation. A human LIM-HOX gene, namely hLH-2, was highly expressed in chronic myelogenous leukemia (CML) and located on chromosome 9q33-34.1, in the same region as the reciprocal translocation that creates the Bcr-Abl chimera of Philadelphia chromosome (H.-K. Wu et al., 1996, Oncogene 12, 1205-1212). To elucidate the mechanism of hLH-2 transcriptional activation, we studied the methylation status of hLH-2 in normal bone marrow and CML cells. When blots containing genomic DNA digested with Hpa II or Msp I were hybridized with full-length cDNA probe, it was discovered that hLH-2 was methylated in normal bone marrow cells in which hLH-2 was not expressed; in contrast, both alleles of the hLH-2 locus in CML cells were heavily hypomethylated. Furthermore, using a sensitive RT-PCR technique, we examined the expression of LH-2 in mouse x human hybrids and a wide array of mouse cell lines containing Abl or Bcr-Abl, and we failed to identify a consistent expression pattern in the cell lines tested. These results suggest that the transcriptional activation of hLH-2 in CML is likely due to a cis-acting effect, but not a trans-acting effect, of the Bcr-Abl fusion protein. Because hypomethylated genes generally are transcribed more efficiently than hypermethylated genes, the high level of hLH-2 mRNA in CML cells probably is a consequence of the low level of methylation of the gene in the leukemic cells.


A polymorphism in the glucokinase gene that raises plasma fasting glucose, rs1799884, is associated with diabetes mellitus and prostate cancer: findings from a population-based, case-control study (the ProtecT study).
Epidemiological studies have identified a positive association between prostate cancer and recent onset type 2 diabetes mellitus but an increasingly inverse association with greater duration of type 2 diabetes. The mecha- nisms underlying these paradoxical associations are not clear. A single nucleotide polymorphism in the glucokinase gene, rs1799884, is associated with higher circulating plasma fasting glucose and with an increased risk of type 2 diabetes. We report a case-control study nested within the population-based Prostate testing for cancer and Treatment (ProtecT) study ISRCTN20141297. Men aged 50-69 years based around 9 UK cities were invited for a prostate specific antigen (PSA) test between June 2002 and November 2006. 1,551 cases and 2,993 controls were geno-typed. We observed suggestive evidence for a positive association between the AA variant rs1799884 and PSA-detected prostate cancer (OR(AA V GG)= 1.40, 95% CI= 0.95 to 2.07). There was little evidence that this effect was greater for more advanced stage/ grade cancers (OR(AA V GG)= 1.78, 95% CI= 0.99 to 3.21) versus less advanced cancers (OR(AA V GG)= 1.23, 95% CI= 0.77 to 1.94) (p for interaction = 0.33). The rs1799884 genotype was not associated with PSA concentration, suggesting that any effect on prostate cancer risk is not attributable to PSA detection bias. Our results provide suggestive evidence for a link between a genotype associated with type 2 diabetes mellitus and PSA-detected prostate cancer. We hypothesize that hyperglycaemia may be important in mediating this relationship.


Mixed-Phase 2D-MoS2 as an Effective Photocatalyst for Selective Aerobic Oxidative Coupling of Amines under Visible-Light Irradiation.
Metal-semiconductor heterojunctions play a vital role in photocatalysis, yet their preparation can be exceedingly difficult. The heterojunction helps not only to separate the charges and inhibit recombination processes but also to transfer the photogenerated electron/hole to the reacting molecule. Here, we demonstrate 1T (metallic)-2H (semiconducting) phase boundaries intrinsic to individual sheets of chemically exfoliated 2D-MoS2 can serve as heterojunctions for enhanced photocatalysis in comparison to only semiconducting phase. Due to the abundance of heterojunctions in these multiphasic materials, chemically exfoliated 2D-MoS2 provides improved stability and transfer of photogenerated charges to the reactants, giving better yield. We demonstrate that this easy to synthesize material is an effective photocatalyst for the aerobic oxidative coupling of amines to imines under visible light irradiation. Given its broad applications, we believe mixed phase 2D-MoS2 can be of interest to several industrial synthetic applications related to semiconductor-based photocatalysis. As an added advantage, this heterogeneous photocatalyst can be recycled for several times up to five cycles without any significant loss in the activity.