Dispatch of a helicopter emergency medicine service to patients with a sudden, unexplained loss of consciousness of medical origin.
Sudden loss of consciousness (LOC) in the prehospital setting in the absence of cardiac arrest and seizure activity may be a challenge from a dispatcher's perspective: The aetiology is varied, with many causes being transient and mostly self-limiting, whereas other causes are potentially life threatening. In this study we aim to evaluate the dispatch of HEMS to patients with LOC of medical origin, by exploring to which patients with a LOC HEMS is dispatched, which interventions HEMS teams perform in these patients, and whether HEMS interventions can be predicted by patient characteristics. We performed retrospective cohort study of all patients with a reported unexplained LOC (e.g. not attributable to a circulatory arrest or seizures) attended by the Air Ambulance Kent, Surrey & Sussex (AAKSS), over a 4-year period (July 2013-December 2017). Primary outcome was defined as the number of HEMS-specific interventions performed in patients with unexplained LOC. Secondary outcome was the relation of clinical- and dispatch criteria with HEMS interventions being performed. During the study period, 127 patients with unexplained LOC were attended by HEMS. HEMS was dispatched directly to 25.2% of the patients, but mostly (74.8%) on request of the ground ambulance crews. HEMS interventions were performed in 65% of the patients (Prehospital Emergency Anaesthesia 56%, hyperosmolar therapy 21%, antibiotic/antiviral therapy 8%, vasopressor therapy 6%) and HEMS conveyed most patients (77%) to hospital. Acute neurological pathology was a prevalent underlying cause of unexplained LOC: 38% had gross pathology on their CT-scan upon arrival in hospital. Both GCS (r = - 0.60, p < .001) and SBP (r = 0.31, p < .001) were related to HEMS interventions being performed on scene. A GCS < 13 predicted the need for HEMS interventions in our population with a sensitivity of 94.9% and a specificity 75% (AUC 0.85). HEMS dispatchers and ambulance personnel are able to identify a cohort of patients with unexplained LOC of medical origin who suffer from potentially life threatening (mainly neurological) pathology, in whom HEMS specific intervention are frequently required. Presenting GCS can be used to inform the triage process of patients with LOC at an early stage.


An attempt to select pseudonormal revertants of Friend erythroleukaemia cells using cytochalasin B.
Treatment of Friend erythroleukaemia cells with cytochalasin B (CB) resulted in multinucleation and loss of viability characteristic of a virus-transformed cell line. In an attempt to isolate pseudonormal revertants of this cell line mutagenized cultures were exposed to CB and surviving clones isolated. Many of these were found to be mutants resistant to the growth inhibitory effects of CB. The proportion of such mutants was reduced by simultaneous selection in CB and cytosine arabinoside. Of 699 clones examined none consistently exhibited reduced levels of multinucleation in the presence of CB. The inability of CB to select for revertants displaying a phenotype closer to normal cells is discussed.


Utility of respiratory-gated small-animal PET/CT in the chronologic evaluation of an orthotopic lung cancer transplantation mouse model.
Our aim in this study was to clarify the effects of respiratory-gated PET in the evaluation of lung cancer according to the (18)F-FDG uptake in an orthotopic transplantation mouse model. We created such a model, and we performed PET/CT. The mice were divided into two groups according to tumor volume: a small-tumor group (<20 mm(3)) and a large-tumor group (>20 mm(3)). We reconstructed the following conditions based on list-mode data: non-gated (3D) images and gated (4D) images, divided based on the respiratory cycle (expiration phase, stable phase, and inspiration phase). We calculated the maximum standardized uptake values (SUVmax) in each phase. We used the % difference [= (4D SUVmax - 3D SUVmax)/3D PET SUVmax × 100 (%)] to evaluate the differences in the 4D SUVmax and 3D SUVmax. The 4D SUVmax values were significantly higher than the 3D SUVmax, regardless of the tumor size. The % difference for the small tumors was greater than that for the large tumors, and it was highest in the stable phase. We conclude that the SUVmax in the stable phase under respiratory-gated PET are the most reliable. The SUVmax observed under non-gated PET are considered to be more frequently underestimated in cases involving small tumors than in those involving large tumors. In the chronologic study evaluating the time course of tumor development, the size of the tumor is small in early stage, and respiratory-gated PET is effective in reducing the underestimation of such tumors caused by respiratory motion.


Application of mathematical models to metronomic chemotherapy: What can be inferred from minimal parameterized models?
Metronomic chemotherapy refers to the frequent administration of chemotherapy at relatively low, minimally toxic doses without prolonged treatment interruptions. Different from conventional or maximum-tolerated-dose chemotherapy which aims at an eradication of all malignant cells, in a metronomic dosing the goal often lies in the long-term management of the disease when eradication proves elusive. Mathematical modeling and subsequent analysis (theoretical as well as numerical) have become an increasingly more valuable tool (in silico) both for determining conditions under which specific treatment strategies should be preferred and for numerically optimizing treatment regimens. While elaborate, computationally-driven patient specific schemes that would optimize the timing and drug dose levels are still a part of the future, such procedures may become instrumental in making chemotherapy effective in situations where it currently fails. Ideally, mathematical modeling and analysis will develop into an additional decision making tool in the complicated process that is the determination of efficient chemotherapy regimens. In this article, we review some of the results that have been obtained about metronomic chemotherapy from mathematical models and what they infer about the structure of optimal treatment regimens.


InCoB celebrates its tenth anniversary as first joint conference with ISCB-Asia.
In 2009 the International Society for Computational Biology (ISCB) started to roll out regional bioinformatics conferences in Africa, Latin America and Asia. The open and competitive bid for the first meeting in Asia (ISCB-Asia) was awarded to Asia-Pacific Bioinformatics Network (APBioNet) which has been running the International Conference on Bioinformatics (InCoB) in the Asia-Pacific region since 2002. InCoB/ISCB-Asia 2011 is held from November 30 to December 2, 2011 in Kuala Lumpur, Malaysia. Of 104 manuscripts submitted to BMC Genomics and BMC Bioinformatics conference supplements, 49 (47.1%) were accepted. The strong showing of Asia among submissions (82.7%) and acceptances (81.6%) signals the success of this tenth InCoB anniversary meeting, and bodes well for the future of ISCB-Asia.


Improvement of metabolic control does not normalize auditory brainstem latencies in subjects with insulin-dependent diabetes mellitus.
In our previous study (Am J Otolaryngol 14:413-418, 1993), we reported that prolonged auditory brainstem response latencies are associated with microvascular complications and the duration of diabetes in patients with insulin-dependent diabetes mellitus (IDDM). To investigate whether short-term improvement in metabolic control also affects ABR-responses, we compared ABR-latencies in subjects with IDDM before and after intensified insulin and diet therapy. Auditory brainstem latencies were measured in 13 subjects with IDDM (mean age: 25 years) before and after intensified insulin and diet therapy. The acoustic stimulus was a half sine wave with a duration of 0.250 millisecond and a frequency of 2,000 Hz. The stimulus was presented monaurally with fixed polarity through shielded headphones TDH-39 at repetition rate of 10 Hz and at 90 dB hearing level. All subjects had normal hearing ability. Glycated hemoglobin A1C (GHbA1C), blood glucose immediately before ABR-measurements, and mean blood glucose during 24 hours before auditory studies were measured before and after intensified therapy. During intensified insulin therapy, GHbA1C improved significantly (P < .05) in study subjects. However, no changes were observed in ABR-latencies. We also studied those 10 patients whose blood glucose improved during intensified insulin therapy. Although blood glucose was significantly lower (P < .01) after intensified insulin therapy compared with that at baseline, no changes were observed between ABR-latencies at baseline and follow-up. ABR-latencies were not affected by improvement in metabolic control in patients with IDDM. Our finding suggests that delayed ABR-latencies found in patients with IDDM are not caused by poor metabolic control of diabetes but rather by other mechanisms, for example, microvascular complications.


Roles of dry friction in the fluctuating motion of an adiabatic piston.
The motion of an adiabatic piston under dry friction is investigated to clarify the roles of dry friction in nonequilibrium steady states. We clarify that dry friction can reverse the direction of the piston motion and causes a discontinuity or a cusplike singularity for velocity distribution functions of the piston. We also show that the heat fluctuation relation is modified under dry friction.


Preliminary exposure assessment of deoxynivalenol and patulin in South Africa.
Deoxynivalenol (DON) and patulin (PAT) are mycotoxins widely regulated internationally. DON is frequently found in cereals, whereas PAT is commonly found in apple juices. A survey of South African commercial products was conducted on DON levels in maize meal and wheat flours, and on PAT levels in apple juices. DON levels in 23 wheat flour samples (mean of 16 positives, 29 µg/kg) were equal to or below 100 µg/kg and in wheat consumers contributed 6-13% of the provisional maximum tolerable daily intake (PMTDI; 1 µg/kg body weight per day) for DON set by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). Sixteen of 18 maize meal samples were contaminated, with a mean for positive samples of 294 µg/kg, and the probable daily intakes ranged from 3.67 µg/kg body weight per day in rural infants to 1.39 µg/kg body weight per day in urban adults. PAT levels in 20 of 30 apple-juice samples were below the detection level of 10 µg/l. Mean of positive samples was 210 µg/l, with three samples exceeding the South African legal limit of 50 µg/l and the highest level (1,650 µg/l) showing the possibility of a brief but high exposure of 37 µg/kg body weight per day (or 9,250% of the JECFA PMTDI of 0.4 µg/kg body weight per day) in young children.


Magnetic field dependence of the distribution of NMR relaxation times in the living human brain.
This study investigates the field dependence of the distribution of in vivo, whole-brain T1 values, and its usefulness for white matter/grey matter segmentation. Results on T1 values are presented on 12 healthy volunteers. T2 and T2* distributions and their field dependence have been measured on the same cohort of volunteers. In this paper, however, only the T2 and T2* results on a single volunteer are presented. The reported field dependence of T2 and T2* values should, therefore, be given less weight than that of T1 times. Relaxation times were measured in vivo on 12 healthy volunteers, using three nearly identical whole-body scanners, operating at field strengths of 1.5, 3, and 4 T and employing nearly identical software platforms and very similar hardware. T1 mapping was performed using TAPIR, a sequence based on the Look-Locker method. T2* mapping was performed with a multi-slice, multi-echo, gradient echo sequence. A multi-slice, multi-echo T2 mapping sequence based on the Carr-Purcell-Meiboom-Gill (CPMG) method was used to map T2. For each volunteer, the global distribution of T1 relaxation times was described as the superposition of three Gaussian distributions. The field and age-dependence of the centroids and widths of the three Gaussians was investigated. The segmentation of the brain in white and grey matter was performed separately for each field strength. Using the T1 segmentation and the fact that all maps were coregistered, we investigated the distribution of T2 and T*(2) values separately for the white and grey matter and described them with a Gaussian distribution in each case. Multi-slice quantitative maps were produced for the relaxation parameters T1 (near whole-brain coverage with 41 slices), T2* (whole-brain coverage, 55 slices), and T2 (27 slices). A clear age dependence was identified for grey matter T1 values and correlated with similar behaviour observed in a separate study of the brain water content. The increase with field strength of the bulk white and grey matter T1 values was well reproduced by both Bottomley's [1] and Fischer's [2] formulae, with parameters taken from the literature. The separation between the centroids was, however, either overestimated or underestimated by the two formulae. The width of the T1 distributions was found to increase with increasing field. The study of the field dependence of the NMR relaxation times is expected to allow for better differentiation between regions which are structurally different, provide a better insight into the microscopic structure of the brain and the molecular substrate of its function.


Final incision size after cataract surgery with toric intraocular lens implantation using 2 techniques.
To analyze the changes in incision sizes after implantation of a toric intraocular lens (IOL) using 2 methods. Department of Ophthalmology, Clínica Universidad de Navarra, Pamplona, Spain. Prospective case series. Coaxial phacoemulsification and IOL implantation through a 2.2 mm clear corneal incision using a cartridge injector were performed. Wound-assisted or cartridge-insertion techniques were used to implant the IOLs. The results were analyzed according to IOL spherical and cylindrical powers. Corneal hysteresis (CH) and the corneal resistance factor (CRF) were measured and evaluated based on the changes in incision size. Incision size increased in 30 (41.7%) of 72 eyes in the wound-assisted group and 71 (98.6%) of 72 eyes in the cartridge-insertion group. The mean incision size after IOL implantation was 2.27 mm ± 0.06 (SD) and 2.37 ± 0.05 mm, respectively (P<.01). The final incision size and IOL spherical power in the wound-assisted technique group (P=.02) and the cartridge-insertion technique group (P=.03) were correlated significantly; IOL toricity was not (P=.19 and P=.28, respectively). The CH and CRF values were not correlated with the final incision size. The final incision size and the changes in incision size after IOL implantation were greater with the cartridge-insertion technique than with the wound-assisted technique. The increase was related to IOL spherical power in both groups but not to IOL toricity. Corneal biomechanical properties were not correlated with the final incision size.


Improving influenza vaccination rates by targeting individuals not seeking early seasonal vaccination.
Influenza morbidity and mortality remain high in the United States although vaccination clearly improves health outcomes and reduces health expenditures. This study was designed to assess the effectiveness of mail and telephone reminder strategies on improving existing clinic influenza vaccination rates among those not seeking early seasonal vaccination. In mid-November, we randomized 1371 patients at a hypertension clinic into 1 of 2 intervention groups, a mail reminder group (letter plus the Centers for Disease Control [CDC] Influenza Vaccine Information Statement) or a phone reminder group (same information via a personal phone call), or a control group. The following spring, records were reviewed for vaccination documentation. Patients without documentation were contacted by phone to identify whether vaccination for the current season had been obtained. The final analysis included 884 patients (62% women, mean age 57.2 years old): 325 in the mail reminder group, 246 in the phone reminder group, and 313 represented the control group. Overall, 388 of these patients (44%) were vaccinated. Vaccination rates were significantly higher in the intervention groups, 46% for the mail reminder group (age and sex adjusted odds ratio [OR], 1.8, 95% confidence interval [CI], 1.3-2.5; P=.001) and 56% for the phone reminder group (OR, 2.8; 95% CI, 1.9-4.0; P<.0001), compared to 33% in the control group. Both interventions increased vaccination rates in all age/sex groups. In contrast to earlier studies, this intervention occurred later in the influenza vaccination period excluding those who seek early vaccination and allowing interventions to target those less likely to receive vaccination. Compared to previous studies demonstrating only trivial or modest benefits, both mail and phone reminders effectively increased clinic vaccination rates in our group of patients.


Production of patulin and griseofulvin by a strain of Penicillium griseofulvum in three different media.
Production of patulin and griseofulvin by a strain of Penicillium griseofulvum is described. Mycelial dry weight, pH and production of patulin and griseofulvin were assayed in a minimal and a complete medium; patulin or griseofulvin production was assayed in apple juice.


Uterocervical angle measurement for preterm birth prediction in singleton pregnant women with no history of preterm birth and normal cervical length: A prospective cohort study.
To evaluate the ability of second trimester uterocervical angle (UCA) to predict spontaneous preterm birth (sPTB) in low-risk singleton pregnant women. Transvaginal sonographies were performed in the second trimester of 450 singleton pregnant women with no history of sPTB and no history of second trimester miscarriage with normal cervical length (CL) who attended antenatal care at Songklanagarind Hospital, a tertiary teaching hospital in southern Thailand. Gestational ages at delivery were recorded then the UCA values were evaluated according to sPTB occurrence. The differences in mean values of UCA between sPTB and full-term groups were evaluated using t-test. A receiver operating characteristics (ROC) curve was used to assess the ability of UCA to predict sPTB. After excluding women with unknown pregnancy outcomes or missing UCA images, the sPTB rate was 34/421 (8.1 %). In women with anteflexed uterus, the mean UCA value was wider in the sPTB group compared to those with term birth if the measurements were performed at GA 19.5-24 weeks (sPTB group, 123.4°vs controls, 104.3°; P = 0.017). The ROC curve showed an area under the curve (AUC) of 0.7045. The optimal UCA cut-off value was ≥110 degrees, which gave a sensitivity of 83.3 % and a specificity of 61.2 %. The positive predictive value (PPV) was 16.7 %, negative predictive value (NPV) 97.5 %, positive likelihood ratio (LR+) 2.2 and negative likelihood ratio (LR-) 0.3. The UCA in the second trimester is not a good predictor of sPTB in low risk pregnant women.


Prenatal diagnosis of liver and biliary tract disease.
The diagnosis and detection of some forms of liver and bile duct disease have become possible since the adoption of routine fetal ultrasound scanning in the UK, and the remarkable advances in molecular biological techniques. Nevertheless, although antenatal detection may well have improved, it remains difficult to offer a specific diagnosis, much less a prognosis, in most cases. Cystic dilatation of the biliary tree is probably the most common finding. This may be due to cystic choledochal malformations or, occasionally but crucially, biliary atresia. Postnatal investigations (such as ultrasonography, magnetic resonance cholangiography and liver histology) must take the latter possibility into account, as early surgery is the key to a successful outcome following reconstructive biliary surgery. Antenatally diagnosed liver tumours are usually of vascular origin and have an unpredictable natural history. Some may cause fetal cardiac failure and are candidates for in-utero intervention, but in all likelihood, a large proportion will resolve without specific therapy.


Effectiveness of nonocclusive ligature and fenestration used in Baerveldt aqueous shunts for early postoperative intraocular pressure control.
The authors determined the effectiveness of two different methods of modification of Baerveldt aqueous shunts in the control of early postoperative intraocular pressure. The authors retrospectively reviewed charts of 122 eyes of 113 patients who underwent a Baerveldt 350-mm(2) modified with tube fenestration and charts of 129 eyes of 122 patients who underwent a Baerveldt 350-mm(2) modified with a nonocclusive ligature to examine early postoperative intraocular pressure control. In the fenestration group, the tube was modified with a 4-0 intraluminal suture and an occlusive 6-0 external polyglactin ligature before ocular placement. After ocular placement, the tube was further modified with one to three perforating fenestrations. In the nonocclusive-ligature group, the tube was modified with a 4-0 nylon intraluminal suture with a nonocclusive 6-0 external polyglactin ligature before ocular placement. A total of 94 eyes (77%) achieved adequate intraocular pressure control with or without adjunctive medications and. A total of 28 eyes (23%) had postoperative hypertension or hypotony in the fenestration group versus 81 (62.8%) and 48 (37.2%) eyes in the nonocclusive-ligature group (P = 0.014), respectively. The mean change in intraocular pressure preoperatively and 3 months postoperatively was 18.2 mm Hg versus 21.0 mm Hg (P = 0.11) in the fenestration and nonocclusive-ligature groups, respectively. Both the nonocclusive ligature and the fenestration methods provide desirable decreases in intraocular pressure in the immediate postoperative period and 3 months postoperatively; however, the fenestration modification may achieve adequate intraocular pressure control more often in the early postoperative period.


Semiquantitative grading of mitral regurgitation by color-coded Doppler echocardiography.
We evaluated patients with mitral regurgitation by color-coded Doppler echocardiography using a semiquantitative score system, which is useful in the clinical setting, by providing rapid discrimination between mild, moderate and severe regurgitation. The study was performed in 42 patients (19 female, 23 male) mean age 58 years, range 23-75 years with mitral regurgitation of different etiology. Color-coded Doppler measurements were compared to angiographic findings using a three point score system. In addition to such parameters as maximal jet length, area and the ratio jet area/left atrial area, we also considered the duration of regurgitant flow. The best correlation was obtained for the maximal area of the jet multiplied by the duration of regurgitant flow/cycle length (r = 0.88), determined in the apical plane where the jet was best visualized. For the parameter area of jet alone, the correlation coefficient was 0.81, for the length of the jet the value was r = 0.65 and comparison of the areas of jet and left atrium gave a coefficient of 0.77. A clear separation between mild and severe regurgitation was observed only for the parameter calculated by multiplying the area of the jet by the duration of mitral regurgitation. In only 7% of the patients with moderate and severe regurgitation could we observe an overlap. This parameter, therefore, represents a useful method for estimating in a semiquantitative manner the severity of mitral regurgitation by color-coded Doppler echocardiography.


A study of career choice patterns among Canadian medical students.
The number of students pursuing general surgery (GS) has declined in Canada. The reasons for this, and program directors' (PDs) perception of it, are unclear. A survey was distributed to medical students at Queen's University and the University of Manitoba, and to all Canadian GS program directors to explore causes for the trend and identify potential solutions. Students pursuing GS were more likely to feel that GS fit their lifestyle needs (P < 0.05) and to have met positive role models (P < 0.05). Hardship of the training and practice, length of training, need for prestige, income and enjoyment of procedures did not correlate with specialty choice. Half of GS PDs did not perceive a decline in the number of applicants. Attention to student-raised concerns regarding GS programs and increased awareness of the applicants' trends among PDs can be used to address the current decline in applications to GS.


The effect of bezafibrate on the fibrinolytic enzyme system and the drug interaction with racemic phenprocoumon.
The influence of a new hypolipidaemic agent, bezafibrate, on anticoagulant requirements and fibrinolysis was studied in 15 patients with hyperlipidaemia on long-term treatment with racemic phenprocoumon. Our results suggest a dose-dependent augmentation of the anticoagulant response to the coumarin drug. Treatment with bezafibrate at 450 and 600 mg daily required a reduction of the phenprocoumon dose by 18.5 and 33.5%, respectively. Correspondingly, the serum level of phenprocoumon decreased by 11.6 and 35.3%. No evidence for an altered drug elimination of racemic phenprocoumon could be found during treatment with bezafibrate. The results support the hypothesis that bezafibrate and analogous hypolipidaemic drugs enhance the response to oral anticoagulant drugs by increasing the affinity of the receptor site for coumarins or the rate of degradation of the vitamin-K-dependent clotting factors. The investigation of the fibrinolytic enzyme system demonstrated an increase of the fibrinolytic activity by enhancing the activity of the plasminogen activator. The lysis time for euglobulin clot was reduced significantly, plasma fibrinogen only moderately. The antiplasmin activity could not be altered substantially by a decrease of alpha1-antitrypsin and a slight increase of alpha2-macroglobulin. In contrast with the inhibition of platelet function the effect of bezafibrate on the fibrinolytic enzyme system showed no dose dependence.


Endocardial pacemakers in children: lead length and allowance for growth.
Permanent endocardial pacing in small children is feasible but is limited by two problems: sufficient extra lead has to be left within the heart to allow for growth and the excess has to be coiled behind the pacemaker, limiting the benefit from smaller generators. The required intravascular lead length in 120 children and adults was measured on posteroanterior chest X ray and was correlated with standing height. Measurements were made from the mid-point of the left clavicle to the apex of the right ventricle in a curve simulating the usual endocardial lead position. In 60 children, aged 2.0-15.9 years, intravascular lead length (range 15.5-29.0 cm) correlated well with height (0.83-1.70 m), r = 0.91. In 60 adults, mean age 54.9 years, intravascular lead length (25.5-35.6 cm) also correlated well with height (1.45-1.85 m), r = 0.71. In 20 adults the excess extravascular lead length, measured during pacemaker implantation via the subclavian route, was 15.1-33.7 cm and was inversely correlated with height. A child's eventual adult height can be predicted and, using our data, the extra length of lead necessary to allow for growth can be computed. Available endocardial pacing leads are usually 58- to 64-cm long. The excess extravascular lead is a major practical difficulty in children. Shorter leads would avoid the problem of excess lead and facilitate long-term pacing in small children.


Prenatal stress potentiates stress-induced behavior and reduces the propensity to play in juvenile rats.
We examined the hypothesis that prenatal stress potentiates defensive responsiveness which may interfere with the expression of appetitive behavioral activities. Sibling pairs of prenatally stressed and control juvenile rats were placed in an unfamiliar environment. The latency and frequency of social play, a sought-after activity of juvenile rats, were measured on 4 successive days beginning at 25 days of age. However, on Day 27, electric foot shock was administered in order to assess directly whether exposure to threat facilitates the occurrence of defensive behavior in prenatally stressed rats. In addition, to determine whether previous exposure to threat produces long-term suppressive effects on play, rats were retested on Day 28 in the absence of shock. Throughout the testing period, the latency to play, as indicated by one rat pouncing on the opponent, was significantly higher in prenatally stressed than control rats. The frequency of play, however, did not differ reliably between groups. These data suggest that prenatally stressed rats take longer to adapt to the test situation before initiating play than control rats. In both groups, exposure to shock on Day 27 significantly increased the latency to play. More importantly, prenatally stressed rats exhibited significantly higher durations of defensive freezing than control animals. When retested on Day 28, however, the duration of freezing declined significantly and no longer differed between groups. Data appear to support the hypothesis that prenatally stressed juvenile rats are responsive to stress which may modulate the inclination to exhibit social behavior.


Resistance to noise-induced gap detection impairment in FVB mice is correlated with reduced neuroinflammatory response and parvalbumin-positive neuron loss.
Exposure to loud noises results in neuroinflammatory responses in the central auditory pathway. Noise-induced neuroinflammation is implicated in auditory processing deficits such as impairment in gap detection. In this study, we examined whether strain differences between the FVB and C57BL/6 mice in noise-induced impairment in gap detection are correlated with strain differences in neuroinflammatory responses. We found that noise induced more robust TNF-α expression in C57BL/6 than in FVB mice. Noise-induced microglial deramification was observed in C57BL/6 mice, but not in FVB mice. Furthermore, noise exposure resulted in a reduction in parvalbumin-positive (PV+) neuron density in the C57BL/6 mice, but not in FVB mice. These results suggest that neuroinflammatory responses and loss of PV+ neurons may contribute to strain differences in noise-induced impairment in gap detection.


Transketolase inhibition and uremic peripheral sensory neuropathy.
The relationships between predialysis and postdialysis erythrocyte transketolase activities and symptoms of uremic peripheral neuropathy were studied prospectively for 21 months in 19 chronic hemodialysis patients. In all patients the predialysis activity was observed to be sometimes greater and sometimes less than the postdialysis activity. These observations were interpreted as indicating the coexistence in uremic blood of stimulatory and inhibitory substances which influence the enzyme independently. After enzyme stimulation was assumed to be a constant feature of uremia, the expected stimulated activity in erythrocytes of predialysis blood was found to be variably inhibited up to about 55% in these patients. The occurrence of paresthesiae was closely correlated with prolonged erythrocytes transketolase inhibition which in most cases reached a level of about 40%. Our conclusion is that the magnitude of erythroycte transketolase inhibition above a certain minimum level, together with its duration, is associated with symptoms of sensory peripheral neuropathy in the uremic patient. It is therefore predicted that such measurements may be usefully applied in ascertaining the extent of hemodialysis needed to prevent the development of this pathological state.


A new method to predict hospital mortality in severe community acquired pneumonia.
The aim of this study is to develop a new method that is able to accurately predict the 28day hospital mortality in patients with severe community acquired pneumonia (SCAP) at an early stage. We selected 37,348 SCAP patients in ICU from 173 hospitals during 2011.1-2013.12. The predictive factors for 28day hospital mortality were evaluated retrospectively. All cases underwent intensive care, blood routine, blood biochemical tests and arterial blood gas analysis. Under the Classification and Regression Tree (CART) analysis, a new clinical scoring system was developed for early prediction in SCAP patients. The receiver-operating characteristic (ROC) curve was plotted to calculate the area under the receiver operating characteristic curve (AUC). A novel clinical model named CLCGH scoring system, including Serum creatinine (Cr) >259.5μmol/L, leukocyte (WBC)>17.35×109/L, C-reactive protein (CRP)>189.4μg/mL, GCS≤9 and serum HCO3-≤17.65mmol/L, was carried out and each index was an independent factor for hospital mortality in SCAP. In validation cohort, the AUC of the new scoring system was 0.889 for prediction of hospital mortality, which was similar to SOFA score 0.877, APACHEII score 0.864, and was better than the PSI score 0.761 and CURB-65 score 0.767. The new scoring system CLCGH is an efficient, accurate and objective method to predicate the early hospital mortality among SCAP patients.


Frontotemporal dementia as underlying cause of newly altered mental status in a 59-year-old female: a case presentation and literature review.
59 y.o. female is evaluated for chronic behavioral abnormalities. We describe the diagnostic approach to cases of altered mental status. Before considering the different possible etiologies including, for example, metabolic, infectious, toxic, hypoxemic, endocrine, or iatrogenic ones, we underline the importance of assessing patient's baseline functional status. Often, in particular in older patients' population, dementia is the underlying culprit of mentation abnormalities. Through extensive history and with the help of neuroimaging studies, our patient was diagnosed with frontotemporal dementia.


A newly found angiotensin II receptor subtype mediates cyclic GMP formation in differentiated Neuro-2A cells.
In search of the functional role of the newly found angiotensin II (Ang II) binding site which is expressed in differentiated Neuro-2A cells, we found that Ang II causes a marked stimulation of cGMP formation dose-dependently. The stimulation was blocked by the nonselective Ang II receptor antagonist [Sar1,Ile8]Ang II but not by the AT1 antagonist DuP 753 or the AT2 antagonist PD 123319. These results suggest that Ang II increased cGMP level via a new Ang II receptor subtype in differentiated Neuro-2A cells.


Practices and intravascular catheter infection during on- and off-hours in critically ill patients.
The potential relationship between intravascular catheter infections with their insertion during weekend or night-time (i.e., off-hours or not regular business hours) remains an open issue. Our primary aim was to describe differences between patients and catheters inserted during on- versus off-hours. Our secondary aim was to investigate whether insertions during off-hours influenced the intravascular catheter infectious risks. We performed a post hoc analysis using the databases from four large randomized-controlled trials. Adult patients were recruited in French ICUs as soon as they required central venous catheters or peripheral arterial (AC) catheter insertion. Off-hours started at 6 P.M. until 8:30 A.M. during the week; at weekend, we defined off-hours from 1 P.M. on Saturday to 8.30 A.M. on Monday. We performed multivariable marginal Cox models to estimate the effect of off-hours (versus on-hours) on major catheter-related infections (MCRI) and catheter-related bloodstream infections (CRBSIs). We included 7241 patients in 25 different ICUs, and 15,208 catheters, including 7226 and 7982 catheters inserted during off- and on-hours, respectively. Catheters inserted during off-hours were removed after 4 days (IQR 2, 9) in median, whereas catheters inserted during on-hours remained in place for 6 days (IQR 3,10; p < 0.01) in median. Femoral insertion was more frequent during off-hours. Among central venous catheters and after adjusting for well-known risk factors for intravascular catheter infection, we found a similar risk between off- and on-hours for MCRI (HR 0.91, 95% CI 0.61-1.37, p = 0.65) and CRBSI (HR 1.05, 95% CI 0.65-1.68, p = 0.85). Among central venous catheters with a dwell-time > 4 or > 6 days, we found a similar risk for MCRI and CRBSI between off- and on-hours. Similar results were observed for ACs. Off-hours did not increase the risk of intravascular catheter infections compared to on-hours. Off-hours insertion is not a sufficient reason for early catheter removal, even if femoral route has been selected.


The influence of biotic and abiotic factors on banded common loon (Gavia immer) reproductive success in a remote, mountainous region of the northeastern United States.
Habitat degradation resulting from anthropogenic activities can threaten wildlife populations. Even wildlife existing in seemingly pristine areas are at risk of airborne pollutants and urban development. The common loon (Gavia immer), a top-trophic level predator in freshwater aquatic ecosystems, has previously experienced detrimental changes in reproductive success as a result of anthropogenic activities. However, long-term studies and large sample sizes are necessary to ascertain the impacts of various anthropogenic activities on this long-lived species. Using a multi-year dataset, we investigated the effects of multiple biotic and abiotic factors on the probability of adult male and female common loon hatching and fledging success. From 1998-2017, we banded individual loons, collected blood samples to assess mercury (Hg) exposure of the birds, and monitored their reproductive success. Adult female loon hatching success was negatively associated with the amount of rainfall received in a given year while fledging success was positively associated with the amount of shoreline development. Adult male loon hatching success was positively associated with the amount of shoreline development and fledging success was negatively associated with the number of other loon pairs on a lake.


N6-methyladenosine regulated FGFR4 attenuates ferroptotic cell death in recalcitrant HER2-positive breast cancer.
Intrinsic and acquired anti-HER2 resistance remains a major hurdle for treating HER2-positive breast cancer. Using genome-wide CRISPR/Cas9 screening in vitro and in vivo, we identify FGFR4 as an essential gene following anti-HER2 treatment. FGFR4 inhibition enhances susceptibility to anti-HER2 therapy in resistant breast cancer. Mechanistically, m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3β and activates β-catenin/TCF4 signaling to drive anti-HER2 resistance. Notably, suppression of FGFR4 dramatically diminishes glutathione synthesis and Fe2+ efflux efficiency via the β-catenin/TCF4-SLC7A11/FPN1 axis, resulting in excessive ROS production and labile iron pool accumulation. Ferroptosis, a unique iron-dependent form of oxidative cell death, is triggered after FGFR4 inhibition. Experiments involving patient-derived xenografts and organoids reveals a synergistic effect of anti-FGFR4 with anti-HER2 therapy in breast cancer with either intrinsic or acquired resistance. Together, these results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.


Study of crystallization mechanism of Al-based amorphous alloys by in-situ high temperature X-ray diffraction method.
The role of transition metals (TMs) addition on the formation and crystallization of amorphous Al85TMs10Y5 alloys was described using in-situ high-temperature X-ray diffraction. The structural results were compared with differential scanning calorimetry and dynamical mechanical analysis to obtain detailed information about the nucleation and growth of crystalline phases. The performed analysis confirmed that Fe and Cu addition drastically changes the crystallization temperature and the phase composition of the fully crystallized alloys. While for Al85Ni10Y5 alloy, the second crystallization step is related to the formation of Al19Ni5Y3 phase, for Al85(Ni, Fe)10Y5 and Al85(Ni, Fe, Cu)10Y5 alloys crystallization of Al15Fe9Y2 phase was observed. Interestingly, the performed analysis showed that forming a homogenous amorphous phase is not necessary to obtain the best corrosion resistance. It was noted that the precipitation of the YCr2Al20 phase in the Cu-rich amorphous matrix should be a much more interesting approach.


The Expression of c-Myb Correlates with the Levels of Rhabdomyosarcoma-specific Marker Myogenin.
The transcription factor c-Myb is required for modulation of progenitor cells in several tissues, including skeletal muscle and its upregulation is observed in many human malignancies. Rhabdomyosarcomas (RMS) are a heterogeneous group of mesodermal tumors with features of developing skeletal muscle. Several miRNAs are downregulated in RMS, including miR-150, a negative regulator of c-Myb expression. Using the C2C12 myoblast cell line, a cellular model of skeletal muscle differentiation, we showed that miR-150 controls c-Myb expression mainly at the level of translation. We hypothesized that a similar mechanism of c-Myb regulation operates in RMS tumors. We examined expression of c-Myb by immunohistochemistry and revealed c-Myb positivity in alveolar and embryonal tumors, the two most common subgroups of RMS. Furthermore, we showed direct correlation between c-Myb production and myogenin expression. Interestingly, high myogenin levels indicate poor prognosis in RMS patients. c-Myb could, therefore, contribute to the tumor phenotype by executing its inhibitory role in skeletal muscle differentiation. We also showed that c-Myb protein is abundant in migratory C2C12 myoblasts and its ectopic expression potentiates cell motility. In summary, our results implicate that metastatic properties of some RMS subtypes might be linked to c-Myb function.


Nucleoid-mediated positioning and transport in bacteria.
Precise management of the spatiotemporal position of subcellular components is critical to a number of essential processes in the bacterial cell. The bacterial nucleoid is a highly structured yet dynamic object that undergoes significant reorganization during the relatively short cell cycle, e.g. during gene expression, chromosome replication, and segregation. Although the nucleoid takes up a large fraction of the volume of the cell, the mobility of macromolecules within these dense regions is relatively high and recent results suggest that the nucleoid plays an integral role of dynamic localization in a host of seemingly disparate cellular processes. Here, we review a number of recent reports of nucleoid-mediated positioning and transport in the model bacteria Escherichia coli. These results viewed as a whole suggest that the dynamic, cellular-scale structure of the nucleoid may be a key driver of positioning and transport within the cell. This model of a global, default positioning and transport system may help resolve many unanswered questions about the mechanisms of partitioning and segregation in bacteria.


Diagnostic performance of multifocal photopic negative response, pattern electroretinogram and optical coherence tomography in glaucoma.
The photopic negative response of the electroretinogram reflects retinal ganglion cell function and consequently aids diagnosis of optic nerve diseases including glaucoma. In this study, we assessed the efficacy of stimulation parameters for electroretinographic recordings of the multifocal photopic negative response (mfPhNR) for the detection of glaucoma and compared the diagnostic accuracy of electrophysiological, structural and functional measures of glaucoma. We compared the diagnostic performance of the mfPhNR for 6 different stimulation rates in a cohort of 24 controls, 10 glaucoma suspects (GLAS ) and 16 glaucoma participants (GLAG). A cross-modal comparison of the mfPhNR/b wave ratio was performed with the pattern electroretinogram (PERG), and the peripapillary retinal nerve fiber layer (pRNFL) thickness. These analyses were based on area under curves (AUC) obtained from receiver-operating-characteristics (ROC) and step-wise regression analyses. We found that compared to the other mfPhNR-conditions, the PhNR/b-wave ratio for the fastest stimulation condition had the highest AUC for GLAS (0.84, P = 0.008, 95%CI: 0.71- 0.98), while the other modalities, i.e., PERG-amplitude and pRNFL had AUCs of 0.78 (P= 0.039), and 0.74 (P < 0.05), respectively. For GLAG , the respective AUCs were 0.78 (P= 0.004), 0.85 (P< 0.001) and 0.87 (P< 0.001). pRNFL was the significant predictor for both mfPhNR/b-wave ratio [t (48) = 4, P = 0.0002] and for PERG amplitude [t (48) = 3.4, P = 0.001]. In conclusion, fast mfPhNR protocols outperform other multifocal PhNR protocols in the identification of glaucomatous damage especially for GLAS and thus aid the early detection of glaucoma, indicating its value as a surrogate marker of early stage ganglion cell dysfunction.


An anterior longitudinal aortotomy with a distal aortic transection for the arterial switch operation.
An additional longitudinal aortotomy on the anterior aspect of the old ascending aorta after distal aortic transection is very effective for removal of the coronary buttons, prevention of deformation of the neopulmonary arterial ring, and reconstruction of the neopulmonary arterial trunk after the Lecompte maneuver, especially for the neonatal arterial switch operation.


Granulocyte antibodies in leukaemic chronic lymphoproliferative disorders.
The anti-granulocyte activity of serum from patients with B-cell chronic lymphocytic leukaemia (CLL) and other lymphoproliferative disorders was investigated. Granulocyte-binding IgG was measured in 34 patients with CLL, 13 patients with hairy cell leukaemia, one patient with prolymphocytic leukaemia, two patients with Sézary cell leukaemia, and seven patients with chronic T-cell lymphocytosis who had a predominance of circulating large granular lymphocytes. Anti-granulocyte activity was absent in CLL and its variants, but present in the majority of granulocytopenic patients with chronic T-cell lymphocytosis. In one of these patients, granulocytopenia was associated with complement-activating IgG granulocyte antibody. Thus, antibody-mediated granulocyte injury appears to be an unusual occurrence in chronic lymphocytic leukaemia, but is a frequent complication of chronic T-cell lymphocytosis.


Artificial Hsp104-mediated systems for re-localizing protein aggregates.
Spatial Protein Quality Control (sPQC) sequesters misfolded proteins into specific, organelle-associated inclusions within the cell to control their toxicity. To approach the role of sPQC in cellular fitness, neurodegenerative diseases and aging, we report on the construction of Hsp100-based systems in budding yeast cells, which can artificially target protein aggregates to non-canonical locations. We demonstrate that aggregates of mutant huntingtin (mHtt), the disease-causing agent of Huntington's disease can be artificially targeted to daughter cells as well as to eisosomes and endosomes with this approach. We find that the artificial removal of mHtt inclusions from mother cells protects them from cell death suggesting that even large mHtt inclusions may be cytotoxic, a trait that has been widely debated. In contrast, removing inclusions of endogenous age-associated misfolded proteins does not significantly affect the lifespan of mother cells. We demonstrate also that this approach is able to manipulate mHtt inclusion formation in human cells and has the potential to be useful as an alternative, complementary approach to study the role of sPQC, for example in aging and neurodegenerative disease.


Prediction of early and delayed postoperative deaths after coronary artery bypass surgery alone in Italy. Multivariate predictions based on Cox and logistic models and a chart based on the accelerated failure time model.
The aim of the multicenter OP-RISK (OPerative RISK) study was to investigate the early (28 days) and delayed (365 days) death rates following coronary artery bypass grafting (CABG) among patients representing a nationwide distribution [Centers in Northern (2), Central (1) and Southern (1) Italy] and further to define the multivariate risk factors for the early and delayed mortality after CABG. Data were collected from 1126 patients undergoing CABG alone. Data were analyzed using Cox and logistic regression models, to accurately assess the major factors influencing survival over time after CABG. Having defined the significant factors, we constructed a chart of the absolute early risk of mortality using the accelerated failure time model. Using the Cox proportional hazards model and logistic regression we have demonstrated that age, preoperative ejection fraction and heart rate, and the duration of aortic cross-clamping are multivariate risk factors in the short and long term. The role of one arterial conduit was also assessed. The OP-RISK study produced relevant information for risk assessment and control in CABG and the results may form the basis for the objective quality assurance and accreditation of cardiac surgical institutions in Italy. Incidentally, Cox model appeared more adequate than logistic model for the assessment of the major factors influencing survival over time after CABG. The risk factors so assessed were used to construct a chart for practical predictive purposes.


Nematicity with a twist: Rotational symmetry breaking in a moiré superlattice.
Motivated by recent reports of nematic order in twisted bilayer graphene (TBG), we investigate the impact of the triangular moiré superlattice degrees of freedom on nematicity. In TBG, the nematic order parameter is not Ising like, as in tetragonal crystals, but has a three-state Potts character related to the threefold rotational symmetry (C 3z ) of the moiré superlattice. We find that, even in the presence of static strain that explicitly breaks the C 3z symmetry, the system can still undergo a nematic-flop phase transition that spontaneously breaks in-plane twofold rotations. Moreover, elastic fluctuations, manifested as acoustic phonons, mediate a nemato-orbital coupling that ties the nematic director orientation to certain soft directions in momentum space, rendering the Potts-nematic transition mean field and first order. In contrast to the case of rigid crystals, the Fermi surface hot spots associated with these soft directions are maximally coupled to low-energy nematic fluctuations in the moiré superlattice case.


Can you remember silence? Epigenetic memory and reversibility as a site of intervention.
Just over 20 years ago, molecular biologists Leonie Ringrose and Renato Paro published an article with a provocative title, "Remembering Silence", in BioEssays. The article focused on how epigenetic elements could return to their silent state, operationally defined as their epigenetic status before their modulation by experimental or environmental factors. Though Ringrose and Paro's article was on fruit flies and factors affecting embryological growth, the article asked a question of considerable importance to rapidly expanding research in neuroepigenetics on the correlation between trauma and neuropsychiatric risk: If you experience a traumatic event and, as a result, acquire an epigenetic trait that is considered pathological, can you free yourself of that trait? Ultimately, we are interested in how a return to silence is envisioned in neuroepigenetics research, how interventions purported to bring about that silence might function, and what this might mean for people who live in the aftermath of trauma.


Ten-year air sample analysis of Aspergillus prevalence in a university hospital.
Airborne fungal samples were collected on a monthly basis for 10 years, from 1995 to 2005, at a tertiary university hospital. Paired samples were cultured at 25 and 37 degrees C. Data were interpreted according to the air filtration systems serving each location. Samples cultured at 37 degrees C from the patient care areas had a mean recovery of 18% of the mean recovery from outdoor air (22 versus 122cfu/m(3)). Recovery of Aspergillus spp. at 37 degrees C in the high-efficiency particulate air (HEPA)-filtered locations was positive for Aspergillus spp. approximately one-third of the time; the rest of the patient care areas were positive half of the time and the outdoor samples were positive 95% of the time. We found 48 sporadic bursts at 37 degrees C which produced counts >3 SD above the mean. Hospital-acquired infection was related to high recovery of Aspergillus fumigatus on at least one occasion. We have found it impossible, without implementing impractical measures, to provide an environment completely devoid of Aspergillus spp. We conclude that routine air sampling is not an effective means of predicting hospital-acquired infections. However, a transient spike, or burst, may be useful in identifying an in-house source of contamination and may be used to consider additional interventional treatments for patients at risk. Emphasis should be placed on maintaining high-efficiency filtration of the outside air and on ensuring that other environmental control methods are used to prevent dissemination of environmental opportunistic fungal spores.


[A new medical therapeutic approach to cholesteatoma. 5-fluorouracil in local treatment].
The use of applied 5-Fluorouracil is effective in the treatment of cholesteatoma. The authors described the limits of this technique.


Microanalysis for MDR1 ATPase by high-performance liquid chromatography with a titanium dioxide column.
MDR1 is clinically important because it is involved in multidrug resistance of cancer cells and affects the pharmacokinetics of various drugs. Because MDR1 harnesses adenosine 5'-triphosphate (ATP) hydrolysis for transporting drugs, examining the effect on ATPase activity is imperative for understanding the interactions between drugs and MDR1. However, conventional assay systems for ATPase activity are not sensitive enough for screening drugs using purified MDR1. Here we report a novel method to measure ATPase activity of MDR1 using high-performance liquid chromatography equipped with a titanium dioxide column. The amount of adenosine 5'-diphosphate (ADP) produced by the ATPase reaction was determined within 2 min with a titanium dioxide column (4.6 mm ID x 100 mm). The relationship between ADP amount and chromatogram peak area was linear from 5 pmol to 10 nmol. This method made it possible to reduce the amount of purified MDR1 required for a reaction to 0.5 ng, about 1/20th of the conventional colorimetric inorganic phosphate detection assay. This method is sensitive enough to detect any subtle changes in ATPase activity of MDR1 induced by drugs and can be applied to measure ATPase activity of any protein.


Metabolic control through the PGC-1 family of transcription coactivators.
Many complex biological programs are controlled at the level of gene transcription by DNA binding transcription factors. Recent studies have revealed a novel mode of regulation by coactivator proteins, best illustrated by the PGC-1 family of coactivators. These factors are highly responsive to a variety of environmental cues, from temperature to nutritional status to physical activity, and they coordinately regulate metabolic pathways and biological processes in a tissue-specific manner. Notably, the PGC-1 coactivators play a critical role in the maintenance of glucose, lipid, and energy homeostasis and are likely involved in the pathogenic conditions such as obesity, diabetes, neurodegeneration, and cardiomyopathy. These actions also raise new opportunities for the development of novel therapeutics.


pYEMF, a pUC18-derived XcmI T-vector for efficient cloning of PCR products.
A 1330-bp DNA sequence with two XcmI cassettes was inserted into pUC18 to construct an efficient XcmI T-vector parent plasmid, pYEMF. The large size of the inserted DNA fragment improved T-vector cleavage efficiency, and guaranteed good separation of the molecular components after restriction digestion. The pYEMF-T-vector generated from parent plasmid pYEMF permits blue/white colony screening; cloning efficiency analysis showed that most white colonies (>75%) were putative transformants which carried the cloning product. The sequence analysis and design approach presented here will facilitate applications in the fields of molecular biology and genetic engineering.


Porcine acellular dermis-based breast reconstruction: complications and outcomes following adjuvant radiotherapy.
Acellular dermal matrices (ADM) such as StratticeTM are increasingly used in UK during implant-based reconstruction. However, there are mixed opinions regarding the compatibility of radiotherapy treatment in pre- and post-reconstructed breasts. The aims of this study are to audit the rates of radiation induced complications in patients who underwent breast reconstruction using StratticeTM and establish whether there is an association between timing of radiotherapy and complication rates. Retrospective data collection was performed for all patients who underwent skin-sparing mastectomy and immediate or delayed StratticeTM-based reconstruction, and received pre- or post-reconstruction radiotherapy from July 2010 to November 2014. The age ranged from 33 to 78 years (mean age 51 ± 10.6) with a mean follow-up time of 21 months. There were 25 StratticeTM-based reconstructions performed. Sixteen had delayed reconstruction, and 9 had skin-sparing mastectomy and immediate reconstruction. There were 4 (16 %) abandoned procedures due to inability to stretch the mastectomy flap secondary to poor skin compliance. Two women (8 %) presented 4 and 9 months later with wound breakdown. One case (4 %) developed severe capsular contracture following radiotherapy post-reconstruction and 1 case (4 %) of implant rupture. There were no episodes of extrusion or implant infection. Overall complication rates were 32 %. The majority (75 %) of complications occurred in breasts reconstructed post-radiotherapy; however, this is not significant when analysed using chi-square (p = 0.43). Our evidence suggests that there is no difference in complication rates in pre- and post-radiation individuals; this would suggest that implant-based reconstruction using StratticeTM should not be an absolute contraindication in pre- or post-radiotherapy patients. However, when planning these procedures, it is paramount that the increased risks are emphasised to patients in order to better manage patient expectation in cases where complications arise. Level of Evidence: Level III, risk / prognostic study.


Human Acellular Dermal Matrix (Epiflex®) in Immediate Implant-Based Breast Reconstruction after Skin- and Nipple-Sparing Mastectomy and Treatment of Capsular Fibrosis: Results of a Multicenter, Prospective, Observational NOGGO-AWOGyn Study.
Over the last decades, the number of acellular dermal matrix (ADM)-assisted implant-based breast reconstructions (IBBR) has substantially increased. However, there is still a lack of prospective data on complication rates. We performed a non-interventional, multicenter, prospective cohort study to evaluate complication rates of a human ADM in patients undergoing an IBBR after skin- and nipple-sparing mastectomies. Patients with primary reconstruction (cohort A) and patients undergoing a secondary reconstruction after capsular fibrosis (cohort B) using the human ADM Epiflex® (DIZG gGmbH, Berlin, Germany) were enrolled in this study. Patients were followed-up for 12 months after surgery. Eighty-four eligible patients were included in this study of whom 28 women underwent a bilateral breast reconstruction, leading to 112 human ADM-assisted reconstructions in total (cohort A: 73, cohort B: 39). In 33.0% of the reconstructed breasts at least one of the complications of primary interest occurred, including implant loss 7.1%, seroma 15.2%; infection 5.4%, rash 8.0%, and Baker grade III/IV capsular fibrosis 2.7%, with no statistically significant differences between the cohorts. Previous radiation therapy was significantly associated with occurrence of any postoperative complication (OR 20.41; p value 0.027). The rates of most complications were comparable to the rates reported for other ADMs with relatively low rates of capsular fibrosis and infections. The rate of seroma was increased in our study. Prior radiation therapy increased the risk of any postoperative complications. Therefore, the use of ADM in these patients should be considered carefully.


The impact of COVID-19 lockdown on nursing higher education at Chengdu University.
To combat/control the COVID-19 pandemic, a complete lockdown was implemented in China for almost 6 months during 2020. To determine the impact of a long-term lockdown on the academic performance of first-year nursing students via mandatory online learning, and to determine the benefits of online teaching. The recruitment and academic performance of 1st-year nursing students were assessed between 2019 [prior to COVID-19, n = 195, (146 women)] and 2020 [during COVID-19, n = 180 (142 women)]. The independent sample t test or Mann-Whitney test was applied for a comparison between these two groups. There was no significant difference in student recruitment between 2019 and 2020. The overall performance of the first-year students improved in the Biochemistry, Immunopathology, Traditional Chinese Medicine Nursing and Combined Nursing courses via mandatory online teaching in 2020 compared with traditional teaching in 2019. Suspension of in-class learning but continuing education virtually online has occurred without negatively impacting academic performance, thus academic goals are more than achievable in a complete lockdown situation. This study offers firm evidence to forge a path for developments in teaching methods to better incorporate virtual learning and technology in order to adapt to fast-changing environments. However, the psychological/psychiatric and physical impact of the COVID-19 lockdown and the lack of face-to-face interaction on these students remains to be explored.


[Intraoperative radiotherapy (IORT) in the treatment of rectal cancer].
Local recurrence remains one of the most complex problem in the management of rectal carcinoma. Often, surgery alone is not able to prevent local recurrence development, particularly in locally advanced cancer. A better local control is obtained using the association with radiotherapy and chemotherapy. Intraoperative Radiation Therapy (IORT) represents an innovative therapeutic modality. 141 patients, 97 with "high risk" cancer (T2N1-2 or T3N0-2) and 44 with "locally advanced" tumor (T3N3, T4N0-3 or local recurrence). 64 patients with extraperitoneal "high risk" rectal cancer have been treated with preoperative radiotherapy (38 Gy), surgical excision and IORT (10 Gy). In other 33 "high risk" cases, preoperative radio- (50.4 Gy) chemotherapy (Tomudex 2-3 mg), surgery and IORT (10 Gy) have been given. Fourty four patients with "locally advanced" rectal tumor have had external radiotherapy (48 Gy) + chemotherapy (5FU + Mitomicin C) preoperatively, surgery, IORT (10-15 Gy) and chemotherapy (5FU + Levamisolo) postoperatively. Among "high risk" patients, 52-83% of cases have had a sphincter-saving surgical procedure, 5-year local control is 93%, 5-year overall survival 80%, and 5-year disease free survival 77%. In 50-60% of "high risk" tumors treated with preoperative chemo-radiotherapy the pathologic staging have found a T0-1 tumor. Among "locally advanced" primary tumors, 5-year local control is 90.9%, 5-year disease free survival 47.1%, 5-year overall survival 60.7%. Among patients treated for local recurrence, in 60% a complete tumor resection has been performed; 5-year local control is 79.5%, 5-year disease free survival 19.4%, 5-year overall survival 41.4%. Integrated treatment with radiotherapy, chemotherapy, surgery and IORT has allowed a good local control and seems prolong survival also.


Compassionate care: empowering students through nurse education.
Compassionate care is widely discussed in the media, at policy level, in practice and in academic institutions. In order to provide care of this quality, students must be equipped with the skills necessary to build effective relationships with patients and others and to successfully manage the challenges they can encounter in this process. This article describes an evaluation of a teaching approach designed to enhance students' ability to deliver compassionate care. The student voice is used to illuminate their experiences.


Multiple palisaded encapsulated neuromas in siblings: A case report and review of the published work.
Palisaded encapsulated neuroma (PEN) is an uncommon, typically solitary, cutaneous neural neoplasm. Multiple mucocutaneous neuromas are usually seen in multiple endocrine neoplasia (MEN) 2b syndrome. Multiple cutaneous PEN in adult patients with or without features of MEN 2b are extremely rare, with only a few cases described. We report a case of multiple PEN in siblings of the same family with no apparent systemic abnormalities, and review the relevant published work to explore its clinical and pathogenic features and the relationship between multiple PEN and MEN 2b type neuroma (multiple mucocutaneous neuromas seen in MEN 2b syndrome).


A novel in situ method for the detection of deficient transglutaminase activity in the skin.
Autosomal recessive congenital ichthyoses are disorders of epidermal cornification, but are clinically and etiologically heterogeneous. Some cases, known as lamellar ichthyosis, are caused by mutations in the TGM1 gene encoding transglutaminase 1, which result in markedly diminished or lost enzyme activity and/or protein. In some cases, this enzyme is present but there is little detectable activity, and in other clinically similar cases, transglutaminase 1 levels appear to be normal. Since conventional enzyme assays and mutational analyses are tedious, we developed a novel assay for the rapid screening of transglutaminase 1 activity using covalent incorporation of biotinylated substrate peptides into skin cryostat sections. Coupled with immunohistochemical assays using transglutaminase 1 antibodies, our method allows rapid identification of those cases caused by alterations in this enzyme.


Determinants of unemployment in multiple sclerosis (MS): The role of disease, person-specific factors, and engagement in positive health-related behaviors.
Rates of unemployment among individuals with multiple sclerosis (MS) are as high as 80%. This study examines disease, person-specific factors (e.g., personality, self-efficacy), and health-related behaviors, which may account for individuals leaving the workforce. 252 individuals with MS were enrolled in a prospective study examining the factors related to unemployment in MS. Sixty-seven were "at risk" for leaving the workforce. These individuals were compared to those "not at risk" on measures of disease, person-specific factors, and health-related behaviors. Certain disease factors differentiated those "at risk" and those "not at risk." In particular, those "at risk" were more likely to have a progressive course and reported greater fatigue, sleep problems, pain, depression, and anxiety. They also reported lower levels of locus of control and MS self-efficacy and engaging in maladaptive coping. On a measure of personality, they endorsed higher levels of neuroticism and lower levels of conscientiousness, extraversion, and agreeableness. Finally, those "not at risk" reported engaging in more positive health-related behaviors. Taken together, disease course, fatigue, MS self-efficacy, and diet/exercise were the most significant factors, accounting for 16% of the variance. Findings suggest that greater consideration and interventions tailored to these factors is warranted, which may assist individuals with MS staying employed and/or making appropriate accommodations.


Interleukin-1 in multiple myeloma: producer cells and their role in the control of IL-6 production.
We studied the role of interleukin (IL)-1beta in patients with multiple myeloma. By in situ hybridization and immunochemistry, myeloid and megakaryocytic cells expressed high levels of the IL-1beta gene and produced IL-1beta. Myeloma cells less potently expressed the IL-1beta gene and IL-1beta protein. IL-1beta gene expression was not constitutive since it was detected in the bone marrow myeloma cells of two patients, unlike circulating tumoural cells. In addition, nine myeloma cell lines failed to express the IL-1beta gene and this expression could not be induced by 12 different cytokines. We demonstrated that IL-1 was mainly responsible for IL-6 production in the tumoural environment through a PGE2 loop. In fact, an IL-1 receptor antagonist (IL-1RA) blocked PGE2 synthesis and IL-6 production by 80%; this blockage could be reversed by adding synthetic PGE2. Similar findings were found with indomethacin, an inhibitor of cyclooxygenase that blocks PGE2 synthesis. Taken together, these data emphasize the possibility of blocking IL-1 by using IL-1RA or other antagonists in order to block IL-6 production, which is a major tumoural survival and proliferation factor.


Combining radiotherapy and immunotherapy: a revived partnership.
Ionizing radiation therapy (RT) is an important local modality for the treatment of cancer. The current rationale for its use is based largely on the ability of RT to kill the cancer cells by a direct cytotoxic effect. Nevertheless, considerable evidence indicates that RT effects extend beyond the mere elimination of the more radiosensitive fraction of cancer cells present within a tumor at the time of radiation exposure. For instance, a large body of evidence is accumulating on the ability of RT to modify the tumor microenvironment and generate inflammation. This might have far-reaching consequences regarding the response of a patient to treatment, especially if radiation-induced tumor cell kill were to translate into the generation of effective antitumor immunity. Although much remains to be learned about how radiation can impact tumor immunogenicity, data from preclinical studies provide the proof of principle that different immunotherapeutic strategies can be combined with RT to enhance antitumor effects. Conversely, RT could be a useful tool to combine with immunotherapy. This article will briefly summarize what is known about the impact of RT on tumor immunity, including tumor-associated antigens, antigen-presenting cells, and effector mechanisms. In addition, the experimental evidence supporting the contention that RT can be used as a tool to induce antitumor immunity is discussed, and a new approach to radioimmunotherapy of cancer is proposed.


A serial-section study of perforated synapses in rat neocortex.
The morphology of perforated synapses in the molecular layer of rat parietal cortex has been studied in 28-day-old animals. Of the perforated synapses analyzed, 92% were axospinous and of these all had asymmetrical contacts. A spinule was present in 20% of them, and 63% had a negative curvature (concave with respect to the presynaptic terminal) overall. Up to 95% of perforated synapses had one or more negatively-curved segments. The perforated synapses studied were characterized by postsynaptic densities (PSD) with a mean length of 581 nm, compared with 233 nm for non-perforated synapses. A study of over 100 serially sectioned synapses demonstrated that, in perforated synapses, the PSD and perforations often had a highly irregular shape and arrangement, the site of the perforation frequently projected into the presynaptic terminal, and coated evaginations of membrane, or coated vesicles, were sometimes found at the site of a perforation or towards the periphery of perforated PSDs. Preliminary reconstructions of perforated synapses suggest that, for descriptive purposes, three types can be recognized. Criteria are formulated for determining, on the basis of a study of single sections, which non-perforated profiles belong to perforated synapses.


[Estimation of the fetal head-trunk proportion by ultrasound (author's transl)].
Using ultrasonic A- and B-scan equipment, cross-sections of the fetal head and abdomen were recorded in 219 pregnancies of the last trimester. Normal values of the body composition were established by several diameters, the circumferences and the areas. The diagnostic reliability of the different methods is demonstrated in a case report.


Electrocardiographic characteristics of repetitive monomorphic right ventricular tachycardia originating near the His-bundle.
Most idiopathic nonreentrant ventricular tachycardia (VT) and ventricular premature contractions (VPCs) arise from the right or left ventricular outflow tract (OT). However, some right ventricular (RV) VT/VPCs originate near the His-bundle region. The aim of this study was to investigate ECG characteristics of VT/VPCs originating near the His-bundle in comparison with right ventricular outflow tract (RVOT)-VT/VPCs. Ninety RV-VT/VPC patients underwent catheter mapping and radiofrequency ablation. ECG variables were compared between VT/VPCs originating from the RVOT and near the His-bundle. Ten patients had foci near the His-bundle (HIS group), with the His-bundle local ventricular electrogram preceding the QRS onset by 15-35 msec (mean: 22 msec) and His-bundle pacing produced a nearly identical ECG to clinical VT/VPCs. The HIS group R wave amplitude in the inferior leads (lead III: 1.0 +/- 0.6 mV) was significantly lower than that of the RVOT group (1.7 +/- 0.4 mV, P < 0.05). An R wave in aVL was present in 6 of 10 HIS group patients, while almost all RVOT group patients had a QS pattern in aVL. Lead I in HIS group exhibited significantly taller R wave amplitudes than RVOT group. HIS group QRS duration in the inferior leads was shorter than that of the RVOT group. Eight of 10 HIS group patients exhibited a QS pattern in lead V1 compared to 14 of 81 RVOT group patients. HIS group had larger R wave amplitudes in leads V5 and V6 than RVOT group. VT/VPCs originating near the His-bundle have distinctive ECG characteristics. Knowledge of the characteristic QRS morphology may facilitate catheter mapping and successful ablation.


Poly-L-histidine coated microfluidic devices for bacterial DNA purification without chaotropic solutions.
We present a disposable polymeric microfluidic device capable of reversibly binding and purifying Salmonella DNA through solid phase extraction (SPE). The microfluidic channels are first oxygen plasma treated and simultaneously micro-nanotextured, and then functionalized with amine groups via modification with L-histidine or poly-L-histidine. L-Histidine and poly-L-histidine bind on the plasma treated chip surface, and are not detached when rinsing with DNA purification protocol buffers. A pH-dependent protocol is applied on-chip to purify Salmonella DNA, which is first bound on the protonated amines at a pH (5.0) lower than their pKa of surface amine-groups which is 6.0 and then released at a pH higher than the pKa value (10.5). It was found that modification with poly-L-histidine resulted in higher surface density of amine groups onto microfluidic channel. Using the chip modified with poly-L-histidine, high recovery efficiency of at least 550 ng of isolated Salmonella DNA as well as DNA purification from Salmonella cell lysates corresponding to less than 5000 cells or 0.026 ng of Salmonella DNA was achieved. The protocol developed does not require ethanol or chaotropic solutions typically used in DNA purification, which are known inhibitors for downstream operations such as polymerase chain reactions (PCR) and which can also attack some polymeric microfluidic materials. Therefore, the microfluidic device and the related protocol hold promise for facile incorporation in microfluidics and Lab-on-a-chip (LOC) platforms for pathogen detection or in general for DNA purification.


Possible Roles of IL-33 in the Innate-Adaptive Immune Crosstalk of Psoriasis Pathogenesis.
IL-33 belongs to the IL-1 family, playing a role in several biologic processes as well as in the pathogenesis of different diseases, including skin pathologies. It acts as an alarmin, released by damaged cells. Binding to a ST2 receptor, it stimulates many immune cells such as ILC2 and Th2 cells. IL-33/ST2 axis seems to be involved in Th17 response. According to this, a review was performed to analyze if IL-33 even interplay in the onset of psoriasis, a Th1/Th17 inflammatory disease. Data obtained from the included articles are study author name, publication date, group studied, clinical and biological variables, laboratory tests, and outcome of interest of the study. Data are obtained from the 19 studies identified, which assessed the association between IL-33 and psoriasis. It seems to promote the innate-adaptive immune crosstalk: it could induce mast cells and neutrophil response after being released by injured keratinocytes and after stimulation by some cytokines, in particular TNFα, INFγ, and IL-17A. In addition, it seems to be involved from the onset of disease to the development of comorbidities, as psoriatic arthritis. The core of the future research on psoriasis could be to fully understand the role of this complex cytokine, in order also to find a new therapeutic approach.


Characterization of human alcohol dehydrogenase isoenzymes by capillary isoelectric focusing-mass spectrometry.
The human liver alcohol dehydrogenase (ADH) isoenzymes are currently believed to play a major role in ethanol metabolism, accounting for most of the ethanol oxidized in the liver. They have similar molecular masses and similar isoelectric point (pI) values (the 13 possible isoenzymes having pIs in the range of 8.26-8.87), making their characterization a significant analytical challenge. Capillary isoelectric focusing (CIEF) coupled on-line with electrospray ionization - Fourier transform ion cyclotron resonance (ESI-FTICR) mass spectrometry was applied to separate and characterize mixtures of alphaalpha, beta1beta1 and beta3beta3 ADH isoenzymes. Seven different species were resolved by the separation in the pI 8.26-8.67 range. ESI-FTICR analysis of native ADHs revealed that each noncovalent ADH complex contains two monomeric protein units and four zinc atoms. The combination of CIEF separations with mass spectrometry appears well-suited for detailed characterization of ADH isozymes, and the attomole level sensitivity of FTICR should allow very small samples to be addressed.


Mean arterial pressure and vasopressor load after out-of-hospital cardiac arrest: Associations with one-year neurologic outcome.
There are limited data on blood pressure targets and vasopressor use following cardiac arrest. We hypothesized that hypotension and high vasopressor load are associated with poor neurological outcome following out-of-hospital cardiac arrest (OHCA). We included 412 patients with OHCA included in FINNRESUSCI study conducted between 2010 and 2011. Hemodynamic data and vasopressor doses were collected electronically in one, two or five minute intervals. We evaluated thresholds for time-weighted (TW) mean arterial pressure (MAP) and outcome by receiver operating characteristic (ROC) curve analysis, and used multivariable analysis adjusting for co-morbidities, factors at resuscitation, an illness severity score, TW MAP and total vasopressor load (VL) to test associations with one-year neurologic outcome, dichotomized into either good (1-2) or poor (3-5) according to the cerebral performance category scale. Of 412 patients, 169 patients had good and 243 patients had poor one-year outcomes. The lowest MAP during the first six hours was 58 (inter-quartile range [IQR] 56-61) mmHg in those with a poor outcome and 61 (59-63) mmHg in those with a good outcome (p<0.01), and lowest MAP was independently associated with poor outcome (OR 1.02 per mmHg, 95% CI 1.00-1.04, p=0.03). During the first 48h the median (IQR) of the TW mean MAP was 80 (78-82) mmHg in patients with poor, and 82 (81-83) mmHg in those with good outcomes (p=0.03) but in multivariable analysis TWA MAP was not associated with outcome. Vasopressor load did not predict one-year neurologic outcome. Hypotension occurring during the first six hours after cardiac arrest is an independent predictor of poor one-year neurologic outcome. High vasopressor load was not associated with poor outcome and further randomized trials are needed to define optimal MAP targets in OHCA patients.


Photography of medical specimens: experiences from teaching cardiovascular pathology.
Preparation of high-quality 35-mm slides for the teaching of cardiovascular pathology involves little more time and expense than the preparation of poor-quality slides. Attention to proper focusing and exposure times, the use of diffusion screens to eliminate reflections, and the use of nonobtrusive black backgrounds are recommended. Specimens should be fixed before being photographed, and perfusion-fixation is recommended for cases in which tomographic dissections are performed. Hearts dissected by the inflow-outflow method may require pinning so that specific abnormalities may be demonstrated optimally. Lesions may be highlighted with probes and arrows or by comparison with a normal specimen. Use of composite slides is particularly recommended for visual conceptualization of mechanisms and pathogenesis of disease. These techniques are also applicable for the preparation of teaching slides in areas of pathology other than cardiovascular.


Subconjunctival haemorrhage in 147 dogs.
To identify differential diagnoses for subconjunctival haemorrhage in dogs. Retrospective case series. Of 147 dogs with subconjunctival haemorrhage, 119 had a history of trauma. The most common types of injury were vehicular trauma (47/119) and dog attacks (32/119). Confirmed or suspected non-accidental injury was reported for 5/119. Of the 28 dogs without a history of trauma, 13 had a bleeding disorder and of these, immune-mediated thrombocytopenia was the most common diagnosis (9/13). Other causes included seizure disorders (4/28), vasculitis (3/28) and ocular or periocular disease (3/28). Subconjunctival haemorrhage in dogs can be secondary to a wide range of injuries and systemic diseases, bleeding diathesis or ocular disease.


Nedd4 augments the adaptive immune response by promoting ubiquitin-mediated degradation of Cbl-b in activated T cells.
Nedd4 and Itch are E3 ubiquitin ligases that ubiquitinate similar targets in vitro and thus are thought to function similarly. T cells lacking Itch show spontaneous activation and T helper type 2 polarization. To test whether loss of Nedd4 affects T cells in the same way, we generated Nedd4(+/+) and Nedd4(-/-) fetal liver chimeras. Nedd4(-/-) T cells developed normally but proliferated less, produced less interleukin 2 and provided inadequate help to B cells. Nedd4(-/-) T cells contained more of the E3 ubiquitin ligase Cbl-b, and Nedd4 was required for polyubiquitination of Cbl-b induced by CD28 costimulation. Our data demonstrate that Nedd4 promotes the conversion of naive T cells into activated T cells. We propose that Nedd4 and Itch ubiquitinate distinct target proteins in vivo.


The impact of tumor expression of erythropoietin receptors and erythropoietin on clinical outcome of esophageal cancer patients treated with chemoradiation.
To investigate the impact of tumor erythropoietin receptors (Epo-R) and erythropoietin (Epo) expression in 64 patients with Stage III esophageal cancer receiving or not receiving erythropoietin during chemoradiation. The impact of tumor Epo-R expression, Epo expression, and 10 additional factors (age, Karnofsky-Performance-Score [KPS], tumor length, T and N stage, histology and grading, hemoglobin during radiotherapy, erythropoietin administration, surgery) on overall survival (OS) and locoregional control (LC) was evaluated. Improved OS was associated with low (< or =20%) Epo expression (p = 0.049), KPS >80 (p = 0.008), T3 stage (p = 0.010), hemoglobin > or =12 g/dL (p < 0.001), and surgery (p = 0.010). Erythropoietin receptor expression showed a trend (p = 0.09). Locoregional control was associated with T stage (p = 0.005) and hemoglobin (p < 0.001), almost with erythropoietin administration (p = 0.06). On multivariate analyses, OS was associated with KPS (p = 0.045) and hemoglobin (p = 0.032), LC with hemoglobin (p < 0.001). Patients having low expression of both Epo-R and Epo had better OS (p = 0.003) and LC (p = 0.043) than others. Two-year OS was nonsignificantly better (p = 0.25) in patients with low Epo-R expression receiving erythropoietin (50%) than in those with higher Epo-R expression receiving erythropoietin (21%), low Epo-R expression/no erythropoietin administration (29%), or higher Epo-R expression/no erythropoietin administration (18%). Two-year LC rates were, respectively, 65%, 31%, 26%, and 29% (p = 0.20). Results for Epo expression were similar. Higher Epo-R expression or Epo expression seemed to be associated with poorer outcomes. Patients with low expression levels receiving erythropoietin seemed to do better than patients with higher expression levels or not receiving erythropoietin. The data need to be confirmed in a larger series of patients.


An alternative method for the fabrication of a root-supported overdenture: a clinical report.
The preservation of teeth to support an attachment-retained overdenture is an appropriate and stable alternative to extractions and complete dentures. A key to success is the strategic selection of teeth for retention. This clinical report discusses a method for fabricating an overdenture based on a combination of direct and indirect impression techniques. This technique is a simple and time-efficient alternative to traditional methods that aids in overcoming difficulties in fabricating overdentures.


Effect of putative melatonin receptor antagonists on melatonin-induced pigment aggregation in isolated Xenopus laevis melanophores.
The ability of putative melatonin receptor antagonists to antagonise melatonin-induced aggregation of pigment granules in cultured neural crest Xenopus laevis melanophores was examined. Neither ML 23 (N-(2,4-dinitrophenyl)-5-methoxytryptamine) nor 6-methoxy-2-benzoxazolinone showed agonist or antagonist activity. N-Acetyltryptamine and N-butanoyltryptamine were partial agonists; both compounds aggregated pigment granules in some cells, but also reversed melatonin-induced pigment agreggation in a fraction of the cells tested. In contrast, 2-benzyl N-acetyltryptamine (luzindole) did not show agonist activity (upto 10 microM) but did reverse the aggregating action of melatonin at 1 and 10 microM. Pretreatment of melanophores with luzindole shifted the melatonin concentration-response curve to the right.


Comparison of the mode of action of a dinuclear platinum complex containing a pyridine derivative with its monomeric analog.
The DNA binding and interstrand cross-linking properties of the dinuclear platinum complex [¿cis-Pt(NH3)2Cl¿2bpsu](NO3)2 (bpsu is 4,4'-dipyridyl sulfide) (II) and the mononuclear complex [cis-Pt(NH3)2Cl(4-methylpyridine)]NO3 (I) were compared with those of [¿cis-Pt(NH3)2Cl¿2H2N(CH2)4NH2](NO3)2 (III) in order to understand the mode of action of complexes I and II. Both compound I and compound II caused significantly different changes of conformation in poly(dG-dC) x poly(dG-dC) than compound III did. Studies of DNA binding, interstrand cross-linking and fluorescence assay suggest that compound I monofunctionally binds to DNA and compound II bifunctionally binds to DNA, that the dinuclear platinum complex II more efficiently interacts with DNA compared to its monomeric analog, and that platinum I and II complexes both interact with DNA in a non-intercalative mode. All the results indicate that the mode of action of the dinuclear complex II is different from that of the mononuclear complex I.


Human health risk assessment for consumption of microplastics and plasticizing substances through marine species.
A special characteristic of MP (microplastics) in the ocean is they may act as carriers of additives specific to the plastic materials used in their manufacture, such as plasticizers, among which Bisphenol-A (BPA), bis (2-ethylhexyl) phthalate (DEHP), dybuthyl phthalate (DBP). Both MP as the plasticizers were searched in composite samples of mangrove cockle (Anadara tuberculosa), Stolzmann's weakfish (Cynoscion stolzmanni) and arched swimming crab (Callinectes arcuatus). Extraction of MP was done through physical-chemical techniques and identification was carried out employing the techniques of light microscopy, energy dispersive spectrometer (EDS), scanning electron microscope (SEM) and Raman spectroscopy; the sizes of MP obtained were between 0.5 μm and 106 μm, the following average results being obtained: for Arched swimming crab 4.0 ± 1.0 MP/g; mangrove cockle 3.3 ± 2.9 MP/g; and for Stolzmann's weakfish, the average was 2.4 ± 1.3 MP/g; the most observed shapes were fibers and irregular segments; the most identified MP was polyethylene terephthalate (PET). Regarding extraction and quantification of plasticizers, the extraction stage was carried out using QuEChERS tubes; and the identification and quantification with gas chromatography coupled to a mass spectrometer (GC-MS). Regarding the plasticizing substances, DEHP was found in detectable levels in all the samples; BPA was found in 84% of the composite samples analyzed; DBP was found in 50% of them, of the analyzed samples 34% were positive for the 3 analytes. The dietary exposure of people to plasticizers was calculated and for BPA the exposure obtained was compared with respect to the TDI (tolerable intake dose) for pregnant women and the new TDI proposed by EFSA in 2021 according to the estrogenic effect of this substance in the fetus. The objective of the work was to determine if a relationship could be established between both PM and plasticizers, which gave a positive relationship.


Usefulness of pulsed wave tissue doppler imaging in assessment of left ventricular functions in children with beta-thalassemia major.
To evaluate the changes in the LV systolic and diastolic function in children with beta-thalassemia major (β-TM) using pulsed wave tissue doppler (TD) echocardiography. Clinical, conventional echo doppler and pulsed wave tissue doppler imaging parameters were compared in 40 beta-thalassemia major patients (mean age, 6.52 ± 3.5 y) and 25 age and sex matched normal subjects (mean age, 6.5 ± 2.7 y). There were no significant statistical differences between mean fractional shortening (FS) and ejection fraction (EF) of left ventricle (LV) of the patients and control group. Children with beta-thalassemia had significantly lower E' wave velocities measured at the left ventricular septal annulus (8.1 ± 3.3 vs. 13 ± 2.5, P < 0.001), lateral margin of the mitral annulus (9.1 ± 5.4 vs. 13.3 ± 2.5, P < 0.001) and lateral margin of the tricuspid annulus (9.3 ± 3.9 vs. 13.3 ± 2.5, P < 0.001) when compared to the control group. Furthermore children with beta-thalassemia had significantly lower E'/A' wave ratio at the left ventricular septal annulus (0.76 ± 0.34 vs. 1.36 ± 0.23), lateral margin of the mitral annulus (0.83 ± 0.17 vs. 1.28 ± 0.22), and lateral margin of the tricuspid annulus ((0.90 ± 0.27 vs. 1.26 ± 0.23, (P < 0.05) when compared to the control group. This study showed that patients with beta-thalassemia major and normal conventional echo doppler parameters had statistically significant changes detected by pulsed wave tissue doppler imaging.


Patterns of brain activity associated with nostalgia: a social-cognitive neuroscience perspective.
Nostalgia arises from tender and yearnful reflection on meaningful life events or important persons from one's past. In the last two decades, the literature has documented a variety of ways in which nostalgia benefits psychological well-being. Only a handful of studies, however, have addressed the neural basis of the emotion. In this prospective review, we postulate a neural model of nostalgia. Self-reflection, autobiographical memory, regulatory capacity and reward are core components of the emotion. Thus, nostalgia involves brain activities implicated in self-reflection processing (medial prefrontal cortex, posterior cingulate cortex and precuneus), autobiographical memory processing (hippocampus, medial prefrontal cortex, posterior cingulate cortex and precuneus), emotion regulation processing (anterior cingulate cortex and medial prefrontal cortex) and reward processing (striatum, substantia nigra, ventral tegmental area and ventromedial prefrontal cortex). Nostalgia's potential to modulate activity in these core neural substrates has both theoretical and applied implications.


Enhanced immunoprotective potential of Mycobacterium tuberculosis Ag85 complex protein based vaccine against airway Mycobacterium tuberculosis challenge following intranasal administration.
This study examined the role of intranasal vaccination with Mycobacterium tuberculosis antigen85 complex proteins formulated in dimethyldioctadecylammonium bromide against airway Mycobacterium tuberculosis challenge in mice. Intranasal vaccination with antigen85A and antigen85B induced a significantly higher level of interferon-gamma, interleukin-12 and interleukin-4 in cervical lymph nodes together with IgA and IgG, predominantly IgG2a isotype in nasal secretion over subcutaneous vaccination. Further, intranasal vaccination with antigen85A and antigen85B imparted protection comparable with that obtained from intranasal or subcutaneous Mycobacterium bovis bacillus Calmette-Guerin immunization. These results suggest that mucosal vaccination via the intranasal route is of importance in the development of vaccine for tuberculosis.


A Study on the Effects of Release Area on the Quality Factor of Contour-Mode Resonators by Laser Doppler Vibrometry.
Through the use of a laser Doppler vibrometer, it is shown that a 31% variation in quality factor can occur due to the effect of undercutting of the device layers outside of the anchors of a 220-MHz aluminum nitride contour-mode resonator. This undercutting is a result of the isotropic etch process used to release the device from the substrate. This paper shows that the variation in Q is a function of the release distance, L , between the active region of the resonator and the edge of this released region. This paper also determined a design modification that eliminated this issue and achieved a Q of 3048, which is independent of L .


Chlamydia trachomatis among patients infected with and treated for Neisseria gonorrhoeae in sexually transmitted disease clinics in the United States.
For two decades, treatment guidelines for sexually transmitted diseases (STDs) have recommended empirical co-treatment for chlamydia when patients are treated for gonorrhea. Because the epidemiology of and diagnostic testing for STDs have changed over time, co-treatment may no longer be needed as a clinical or public health strategy. To assess the prevalence of chlamydia among patients at STD clinics who are infected with and treated for Neisseria gonorrhoeae and to determine whether co-treatment recommendations are still justified. Cross-sectional analysis of data from a multisite study. Five public STD clinics (Baltimore, Maryland; Denver, Colorado; Long Beach, California; Newark, New Jersey; and San Francisco, California), July 1993 through October 1995. 3885 heterosexual patients (2184 men and 1701 women) who agreed to participate in a trial of counseling interventions and had conclusive results from diagnostic tests for gonorrhea and chlamydia performed routinely as part of the trial. Infection with Chlamydia trachomatis as determined by polymerase chain reaction. Chlamydia trachomatis was detected in 20% (95% CI, 16% to 24%) of 411 men and 42% (CI, 35% to 50%) of 151 women with laboratory-confirmed N. gonorrhoeae. Chlamydia trachomatis was detected in 19% (CI, 15% to 22%) of 410 men and 35% (CI, 28% to 43%) of 154 women with treatment indications for gonorrhea who would not otherwise have been treated for chlamydia: chlamydia prevalence among these patients was significantly higher than among patients without treatment indications for either gonorrhea or chlamydia: 7% in men and 9% in women (relative risk, 2.58 [CI, 1.92 to 3.47] and 4.12 [CI, 3.05 to 5.57], respectively). The frequent presence of chlamydia among patients at STD clinics who received treatment for gonorrhea, including sex partners of gonorrhea-infected patients, supports continuing current recommendations for co-treatment.


CAG Repeat Expansion in THAP11 Is Associated with a Novel Spinocerebellar Ataxia.
More than 50 loci are associated with spinocerebellar ataxia (SCA), and the most frequent subtypes share nucleotide repeats expansion, especially CAG expansion. The objective of this study was to confirm a novel SCA subtype caused by CAG expansion. We performed long-read whole-genome sequencing combined with linkage analysis in a five-generation Chinese family, and the finding was validated in another pedigree. The three-dimensional structure and function of THAP11 mutant protein were predicted. Polyglutamine (polyQ) toxicity of THAP11 gene with CAG expansion was assessed in skin fibroblasts of patients, human embryonic kidney 293 and Neuro-2a cells. We identified THAP11 as the novel causative SCA gene with CAG repeats ranging from 45 to 100 in patients with ataxia and from 20 to 38 in healthy control subjects. Among the patients, the number of CAA interruptions within CAG repeats was decreased to 3 (up to 5-6 in controls), whereas the number of 3' pure CAG repeats was up to 32 to 87 (4-16 in controls), suggesting that the toxicity of polyQ protein was length dependent on the pure CAG repeats. Intracellular aggregates were observed in cultured skin fibroblasts from patients. THAP11 polyQ protein was more intensely distributed in the cytoplasm of cultured skin fibroblasts from patients, which was replicated with in vitro cultured neuro-2a transfected with 54 or 100 CAG repeats. This study identified a novel SCA subtype caused by intragenic CAG repeat expansion in THAP11 with intracellular aggregation of THAP11 polyQ protein. Our findings extended the spectrum of polyQ diseases and offered a new perspective in understanding polyQ-mediated toxic aggregation. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.