Physiological effects of etorphine, acepromazine and xylazine in the scimitar horned oryx (Oryx dammah).
Scimitar horned oryx (Oryx dammah), kept under confined and unconfined conditions were immobilised with etorphine in combination with acepromazine or xylazine or both, and with xylazine alone. Both groups of animals were successfully sedated with etorphine and xylzine, with or without acepromazine, although hypothermia and mild hypoxaemia and a fall in packed cell volume were frequently noted. Xylazine alone produced a dose dependent degree of sedation in semitame subadult animals kept in confinement, but only slight depression in their wild, unconfined counterparts. If xylazine was not included in the immobilising mixture induction was traumatic and full sedation not achieved. Heart rates and arterial pressures (systemic and pulmonary) were also monitored but no remarkable changes were noted. The only abnormalities in blood biochemistry were raised aspartate transminase and creatine kinase. Ruminal regurgitation could be a major problem if endotracheal intubation was not achieved early in the procedure.


The potential of a salt-tolerant plant (Distichlis spicata cv. NyPa Forage) to treat effluent from inland saline aquaculture and provide livestock feed on salt-affected farmland.
Dryland salinity is a major problem affecting food production from agricultural land in Australia and throughout the world. Although there is much interest in using saline groundwater to grow marine fish on salt-affected farmland, the disposal of nutrient enriched, saline aquaculture effluent is a major environmental problem. We investigated the potential of the salt-tolerant NyPa Forage plant (Distichlis spicata L. Greene var. yensen-4a) to trap nutrients from saline aquaculture effluent and subsequently to provide a fodder crop for livestock. Sub-surface flow wetlands containing NyPa Forage were constructed and their efficacy in removing total nitrogen, ammonia, nitrite/nitrate, total phosphorus and orthophosphate was monitored under different levels of nutrients and salinity. The wetlands removed 60-90% of total nitrogen loads and at least 85% of ammonia, nitrite/nitrate, total phosphorus and orthophosphate loads, with greater efficiency at high nutrient and low salinity levels. The above-ground yield, sodium, crude protein (CP) and in vitro dry matter digestibility (DMD) of NyPa Forage plants were measured after fertilisation with different nutrient levels and cropping at different frequencies. Yield of plants increased with increased nutrient, while nutritive value was greater when nutrients were applied but did not differ among nutrient levels. Yield was not affected by cropping frequency, but nutritive value was greatest when plants were cropped at intervals of 21 or 42 days. At optimum nutrient addition and cropping levels, the plants had a mean CP content of 16.7% and an in vitro DMD of 67.6%, equivalent to an energy value of 9.5 MJ kg(-1). Assuming an equivalent fibre content and voluntary food intake as grass hay, and no accumulation of other toxic minerals, these nutritive values would be sufficient for maintenance or moderate liveweight gains in dry adult sheep or cattle.


Ethyl 1H-indole-2-carboxyl-ate.
Our work in the area of synthesis of tris indole compounds as a potential chelator led to the synthesis and crystallization of ethyl 1H-indole-2-carboxyl-ate, C11H11NO2, an indole that was synthesized by the thionyl chloride reaction of 1H-indole-2-carb-oxy-lic acid, followed by dissolution in ethanol. The mol-ecular packing exhibits a herringbone pattern with the zigzag running along the b-axis direction; the compound crystallizes as a hydrogen-bonded dimer resulting from O⋯H-N hydrogen bonds, between the indole N-H group and the keto oxygen atom, which build centrosymmetric R 2 2(10) ring motifs in the crystal.


Low birthweight and mortality in Australian Aboriginal babies at the Royal Darwin Hospital: a 15 year study.
A retrospective analysis was made of all births at the Royal Darwin Hospital from 1 January 1969 to 31 December 1983. The births were divided into weight categories and racial groups (Aboriginal and non-Aboriginal). The study showed that there was a 23.2% incidence of low birthweight (LBW) babies (less than 2500 g) in Aboriginals compared with an incidence of 6.4% in non-Aboriginals. It was found that Aboriginals had a better chance of surviving the neonatal periods than non-Aboriginals of the same birthweight for all birthweights up to 2500 g. It is suggested that this occurred because most LBW Aboriginals were more mature than their birthweight would have suggested. The perinatal and neonatal mortality, however, remains high in the Aboriginal babies and this can also be attributed to the high incidence of LBW babies in this group, and perhaps to the limited use of antenatal care by the Aboriginal mothers.


Adjuvant treatment of meningioma with stereotactic radiation surgery and hypofractionated stereotactic radiation surgery: Patterns of care and survival in a large, hospital database.
Stereotactic radiation surgery (SRS) and hypofractionated stereotactic radiation surgery (HF-SRS) have become an alternative to external beam radiation therapy (EBRT) in the adjuvant treatment of meningiomas. The purpose of this study was to identify national treatment patterns and survival outcomes for meningiomas on the basis of radiation treatment modality in the adjuvant setting. The National Cancer Database was queried for patients with meningioma diagnosed between 2010 and 2012. World Health Organization grade I disease with subtotal resection and all cases of grade II disease regardless of the extent of the resection were included. Logistic regression was used to determine factors that were associated with receipt of SRS/HF-SRS compared with EBRT. Cox regression was used to determine covariables associated with differences in overall survival (OS). A total of 802 patients met the inclusion criteria of which 173 patients received SRS/HF-SRS (22%) and 629 patients (78%) received EBRT. The 3-year OS rate was 97.3% for the SRS/HF-SRS group and 93.4% for the EBRT group (P = .018). On subgroup analysis by grade, for grade I the 3-year OS rate was 98.3% for the SRS/HF-SRS group versus 96.7% for the EBRT group (P = .117). For grade II disease, the 3-year OS rate was 94.4% in the SRS/HF-SRS group versus 92.4% in the EBRT group (P = .199). On multivariable analysis, World Health Organization grade II histology (odds ratio [OR]: 0.34; 95% confidence interval [CI], 0.21-0.56; P < .001) and gross total resection (OR: 0.29; 95% CI, 0.15-0.57; P < .001) were associated with a decreased likelihood of receiving SRS/HF-SRS but private insurance (OR: 8.89; 95% CI, 1.15-68.47; P = .036) and Medicare (OR: 10.03; 95% CI, 1.28-78.69; P = .028) were associated with an increased likelihood of receiving SRS/HF-SRS. Year of diagnosis was not associated with receipt of SRS/HF-SRS. The multivariable Cox regression demonstrated a trend toward improved OS for treatment with SRS/HF-SRS (hazard ratio: 0.24; 95% CI, 0.06-1.03; P = .055). SRS and HF-SRS are associated with similar survival as EBRT; however, SRS/HF-SRS is used infrequently and usage has not increased over time.


Scintimammography with 99mTc-MIBI and magnetic resonance imaging in the evaluation of breast cancer.
This study was performed to evaluate the sensitivity and specificity of technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) scintimammography (SMM) and contrast-enhanced magnetic resonance imaging (MRI) in patients with breast masses, using the histological findings as the gold standard. Forty-five consecutive patients with a breast lesion, detected by self-examination, physical examination or screening mammography, underwent SMM and MRI. In 38 cases (84.5%), the histopathology was malignant; the breast cancers ranged from 3 to 100 mm in diameter (mean 22 mm). In the overall patient group, MRI showed a slightly higher sensitivity than SMM (92% vs 84%), but SMM showed a better specificity: 71% vs 42%. The accuracy was 82% and 84% for SMM and MRI respectively. To evaluate the influence of lesion size on the results, patients with lesions < or =20 mm and < or =15 mm were examined. In patients with lesions < or =20 mm, the sensitivity of SMM and MRI decreased to 64% and 82% respectively, while SMM again displayed considerably better specificity: 83% vs 50% for MRI. The accuracy of SMM and MRI was 64% and 82% respectively. In patients with lesions < or =15 mm, SMM again showed better specificity (75% vs 50%), while MRI displayed better sensitivity and accuracy (sensitivity, 81% vs 62%; accuracy, 75% vs 65%). In this study the specificity of SMM in patients with breast lesions was thus superior to that of MRI. The combination of SMM and MRI may be used in those patients with equivocal findings at mammography and ultrasound to reduce the number of unnecessary surgical biopsies.


Does a traumatic birth experience have an impact on future reproduction?
To investigate whether women's experiences of their first birth affects future reproduction. Prospective cohort study. South Hospital, Stockholm, Sweden. Six hundred and seventeen women who gave birth to their first child 1989-1992. A global measure of women's experiences of their first birth, assessed two months postpartum, was available from a birth centre trial, together with information on a range of background variables. This information was linked to the Swedish Medical Birth Register, which included information on the number of subsequent births during the following 8-10 years. Number of births (0 or > or =1) following the first birth. Women with a negative experience of their first birth had fewer subsequent children and a longer interval to the second baby (RR 1.7, 95% CI 1.3-2.3). Being 35 years and older (RR 2.6, 95% CI 1.6-3.7), or single (RR 2.6, 95% CI 1.7-3.9) was also associated with subsequent infertility. A negative birth experience was associated with subsequent infertility, and women's experiences should therefore be considered seriously in the provision of maternity care.


Active transport of dimethialium in isolated rat hepatocytes.
The uptake of dimethialium, a thiamine analog having a methyl group in place of the hydroxyethyl group in the thiazole moiety, was studied in freshly isolated rat hepatocytes. In an Na+-medium, dimethialium at 10 microM was accumulated rapidly by the cells and an almost steady intra- to extracellular distribution ratio of 4.2 was attained in 5 min of incubation. The Kt and the Vmax for the saturable component were estimated to be 27 microM and 19 pmol/10(5) cells per min, respectively. In a K+ medium, the uptake of dimethialium was decreased to 58% of that of control. Ouabain and 2,4-dinitrophenol significantly lowered the rate of dimethialium uptake. Both phenylthiazinothiamine and oxythiamine were inhibitory on the uptake of dimethialium, which uptake was also inhibited by choline. These data indicate that dimethialium transport in liver cells proceeds via a carrier-mediated active process dependent on Na+ and biological energy. Furthermore, these results also suggest that thiamine transport in liver is dissociable from thiamine phosphorylation.


Contamination in HPLC quantified benzaldehyde is from polypropylene microtubes.
Semicarbazide-sensitive amine oxidase (SSAO; EC 220.127.116.11) is a copper-containing enzyme predominantly expressed by vascular smooth muscle cells. SSAO deaminates primary amines to produce aldehydes and oxygen peroxides, and may thus play a role in vascular damage. SSAO activity can be quantified by assaying benzaldehyde production using fluorescent derivatisation and separation by HPLC. We performed the derivatisation step in polypropylene or borosilicate glass tubes over 45 min at 95 degrees C. High and obstructing background levels of benzaldehyde were found in one batch of polypropylene vials, as opposed to its alternatives. Treatment and handling of product shipment into the country did not account for introduction of contaminant into packaged vials nor did any reagent used in the assay. We conclude that the source of contamination was most likely due to variation in the commercial production process. Use of borosilicate vials for assays based on aldehyde production and derivatisation is recommended.


Blood collection techniques, heparin and quinidine protein binding.
With the use of glass syringes without heparin and all glass equipment, the percent of unbound quinidine was measured by ultrafiltration and a double-extraction assay method after addition of 2 microgram/ml of quinidine sulfate. Compared to the all-glass method, collection of blood using Vacutainers resulted in an erroneous and variable decrease in quinidine binding related to blood to rubber-stopper contact. With glass, the unbound quinidine fraction was (mean +/- standard error) 10 +/- 1% in 10 normal volunteers, 8.5 +/- 1.5% in 10 patients with congestive heart failure, and 11 +/- 2% in 11 patients with chronic renal failure (although in 8 of the latter 11 patients the percent of unbound quinidine was 4 or more standard errors from the mean of the normal group). During cardiac catheterization, patients had markedly elevated unbound quinidine fractions: 24 +/- 2% (p less than 0.001). This abnormality coincided with the addition of heparin in vivo and was less apparent after the addition of up to 10 U/ml of heparin in vitro (120% and 29% increase in unbound quinidine fractions, respectively). Quinidine binding should be measured with all glass or equivalent equipment.


[Septic arthritis after arthroscopic cruciate ligament reconstruction: in vitro comparison of the behavior of two types of interference screws towards the Staphylococcus aureus adherence].
We report the results of an experimental study designed to investigate the behaviour of two types of interference screws (bioabsorbable versus titanium) in a context of Staphylococcus aureus infection. The main objective was to study one of the possible sources of failure for the treatment of acute arthritis of the knee after arthroscopic reconstruction of the cruciate ligament. We used six interference screws made of titanium and six bioabsorbable screws (PLLA-PDLLA). All screws measured 9mmx25mm, were cannulized and sterilized. These screws were submitted to a protocol elaborated in cooperation with the bacteriologists. After contamination with a strain of S. aureus, the screws were washed four times in saline solution to eliminate germs adsorbed in the aqueous phase. The last step was trypsination to detach germs remaining fixed onto the screws and contained in the biofilms of glycocalix. A germ count was made after each step. For each screw, we determined the difference (Delta) corresponding to the number of germs really adherent to the screw. Mann-Whitney analysis was performed. On average, the germ count in the aqueous phase was 0.0855.10(5)/ml for the titanium screw versus 0.223.10(5)/ml for the bioabsorbable screw. The mean count of germs fixed in the biofilm (mean Delta) was 17.695+/-3.88.10(5) for the titanium screw and 45.86+/-3.61.10(5) for the bioabsorbable screw. The difference was statistically significant (p=0.0039). Our experimental results support the efficacy of abundant arthroscopic lavage in a context of infection, confirming the results of very recent studies. However, irrespective of the type of material used, bioabsorbable screws are more prone to persistent microbial adherence than titanium screws. It is hypothesized that the hydrophilic, more porous microstructure of bioabsorbable screws favors bacterial adherence. In practice, this implies that arthroscopic washout must be as abundant and as complete as possible, yet may not be sufficient to clean the entire surface of potentially contaminated screw positioned deep in a bony tunnel.


Blood pressure and outcome after aneurysmal subarachnoid hemorrhage.
Blood pressure management is crucial in the treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). Possible association between the blood pressure increase and the risk of delayed cerebral ischemia (DCI) and different systemic complications after aSAH is still a matter of debate. This study aims to elucidate the influence of blood pressure levels on the outcome of aSAH. All consecutive aSAH patients (n = 690) treated between 01/2003 and 06/2016 were included. The mean value of the mean arterial pressure (MAP) during 14 days after ictus was calculated for each individual. According to the institutional standards of vasospasm management, the mean 14 days MAP ≥ 95 mmHg was referred as increased (IMAP) and the patients with and without vasospasm were analyzed separately. Study endpoints were the occurrence of DCI on computed tomography scans, development of cardiac and nephrological complications, and poor outcome 6 months after aSAH (mRS > 2). Associations were tested in univariable/multivariable binary logistic regression analysis. IMAP was documented in 474 (68.7%) cases and was more common in individuals with poor neurological conditions at admission (p < 0.001), severe amount of intracranial blood (p = 0.001) and premorbid hypertension (p < 0.001). IMAP was independently associated with the occurrence of DCI (p = 0.014; aOR = 2.97; 95% CI 1.25-7.09) and poor functional outcome (p = 0.020; aOR = 3.14; 95% CI 1.20-8.22) in patients with vasospasm, but not in counterparts without vasospasm (p = 0.113/p = 0.086). IMAP had no influence on cardiac or nephrological complications. In aSAH individuals with cerebral vasospasm, sustained increase of blood pressure exceeding the therapeutic targets is strongly associated with the risk of DCI and poor outcome. Therefore, such an intrinsic increase of blood pressure might reflect the autoregulatory mechanisms against the impending cerebral ischemia in patients with cerebral vasospasm.Trial registration number: German clinical trial registry (DRKS, Unique identifier: DRKS00008749, 06/09/2015).


Unilaterally activated systems in rats self-stimulating at sites in the medial forebrain bundle, medial prefrontal cortex, or locus coeruleus.
Rats with electrodes in either the posterior medial forebrain bundle (MFB), the anterior MFB, the medial prefrontal cortex, or the locus coeruleus self-stimulated during a 45 min period following the injection of [14C]2-deoxyglucose. They were then sacrificed and their brains prepared for autoradiography. The autoradiographs were analyzed for unilaterally activated neural systems, using a computerized image analyzing system to compare the darkness of neural structures on the stimulated side with the darkness of the same structures on the unstimulated side. There was extensive overlap in the neural structures unilaterally activated by stimulation in the anterior and posterior MFB; but there was no overlap between the structures activated by MFB stimulation and the structures activated by stimulation at either of the extradiencephalic sites; nor did the forebrain, diencephalic, and midbrain sites have any readily apparent bilateral effects in common. If there is a substrate common to MFB self-stimulation and extradiencephalic self-stimulation, its activation is not revealed by 2-deoxyglucose autoradiography.


Insulin and insulinlike growth factor receptors regulating neurite formation in cultured human neuroblastoma cells.
The functional role of brain insulin and insulinlike growth factor (IGF) receptors is being sought. Recently it has been found that these ligands are members of a newly identified family of neuritogenic polypeptides. We studied the relationship between 125I-insulin and 125I-IGF binding and their capacity to enhance neurite formation in cultured human neuroblastoma SH-SY5Y cells. The binding of 125I-insulin was temperature-dependent and heterogeneous. The Scatchard plot and dissociation rate were both consistent with the presence of two types of sites. There appeared to be about 900 high affinity sites per cell with a Kd of about 3 nM. This compared favorably with the half-maximal concentration of 4 nM for enhancement of neurite formation. The type I IGF sites were also present. Physiologic concentrations of insulin clearly enhanced neurite formation through the insulin sites, whereas physiologic concentrations of IGF-I and IGF-II enhanced through the IGF sites. Cross-occupancy of sites was observed at supraphysiologic concentrations, providing a reasonable explanation for the broad dose-response curves for these ligands. These results support the suggestion that one function of insulin and IGF receptors in neural tissues may be to modulate neurite formation.


Detecting and assessing severity of coronary artery disease in humans.
Quantitation of stenosis severity has become an essential part of cardiac diagnosis and therapy, not only in research but also in clinical practice. Since our introduction of the concept 15 years ago, arterial coronary flow reserve for assessing effects of coronary narrowing has evolved into two independent but complementary measurements: coronary flow reserve and stenosis flow reserve. Coronary artery flow reserve and/or myocardial perfusion reserve takes into account not only stenosis geometry but also collateral function and physiologic conditions of perfusion pressure, vasomotor tone, coronary venous pressure, and myocardial vascular bed size. Coronary artery flow reserve is measured invasively by flowmeter or by Doppler catheter. Its noninvasive equivalent is myocardial perfusion reserve, assessed by myocardial perfusion imaging with positron emission tomography before and after intravenous dipyridamole with hand grip stress. Both have been experimentally and clinically validated for identifying and/or quantifying severity of coronary artery disease. By either invasive or noninvasive methods, coronary artery or myocardial perfusion reserve may be subcategorized as either absolute flow or perfusion reserve (max flow/resting flow) and/or relative flow or perfusion reserve (max flow through stenotic artery/max flow through normal artery). Absolute flow reserve depends not only on stenosis severity but also on unrelated physiologic parameters such as aortic pressure and the vasodilatory state of the distal coronary vascular bed; in contrast, relative flow reserve is independent of these physiologic variables and reflects stenosis severity alone. Stenosis flow reserve is invasively determined by automated, quantitative coronary arteriography accounting for all stenosis dimensions and is independent of ambient physiologic conditions such as pressure, vasomotor tone, or other variables affecting the distal coronary vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)


Cerebral processing of emotional prosody--influence of acoustic parameters and arousal.
The human brain has a preference for processing of emotionally salient stimuli. In the auditory modality, emotional prosody can induce such involuntary biasing of processing resources. To investigate the neural correlates underlying automatic processing of emotional information in the voice, words spoken in neutral, happy, erotic, angry, and fearful prosody were presented in a passive-listening functional magnetic resonance imaging (fMRI) experiment. Hemodynamic responses in right mid superior temporal gyrus (STG) were significantly stronger for all emotional than for neutral intonations. To disentangle the contribution of basic acoustic features and emotional arousal to this activation, the relation between event-related responses and these parameters was evaluated by means of regression analyses. A significant linear dependency between hemodynamic responses of right mid STG and mean intensity, mean fundamental frequency, variability of fundamental frequency, duration, and arousal of the stimuli was observed. While none of the acoustic parameters alone explained the stronger responses of right mid STG to emotional relative to neutral prosody, this stronger responsiveness was abolished both by correcting for arousal or the conjoint effect of the acoustic parameters. In conclusion, our results demonstrate that right mid STG is sensitive to various emotions conveyed by prosody, an effect which is driven by a combination of acoustic features that express the emotional arousal in the speaker's voice.


A novel method to produce hydroxyapatite objects with interconnecting porosity that avoids sintering.
Porous objects of carbonated apatite were prepared by mixing polyvinyl alcohol fibres (PVA) and sodium chloride as porogens with nanocrystalline carbonated apatite powder. After cold isostatic pressing (CIP) and dissolving the porogens, the bioceramic showed an interconnecting porosity with pore diameters in the range of 250-400 microm. The method can be transposed to any material that is insoluble in water (like many polymers). Such objects are promising for bone regeneration because the interconnecting porosity in carbonated apatite provides a good environment for bone attachment and ingrowth.


A deficit profile of executive, memory, and motor functions in schizophrenia.
This study examined the neuropsychological deficits associated with schizophrenia and the interrelationships among multiple dissociable cognitive and motor functions. The tests were selected for their previously demonstrated sensitivity to circumscribed brain pathology and included four functional domains: executive functions, short-term memory and production, motor ability, and declarative memory. Each test composite was divided according to verbal versus nonverbal material or left- versus right-hand performance; this distinction permitted functions principally subserved by the left or right cerebral hemispheres to be tested separately. Data reduction was theoretically driven by the test selection and was achieved first by standardizing the scores of each test for age-related differences observed in the normal control group, and then by calculating test composite scores as an average of the age-corrected Z-scores of the tests comprising a functional composite. The schizophrenic group was impaired equivalently on all composites for both cerebral hemispheres; on average, the Z-scores of the patients were 1 standard deviation below those of the control group. The cognitive test composite scores were highly intercorrelated but showed only weak associations with motor ability. Multiple regression analyses suggested that symptom severity was a significant predictor of the Declarative Memory and Short-Term Memory/Production composite scores after accounting for disease duration, whereas disease duration uniquely contributed to the Executive Functions composite scores after controlling for symptom severity. Even though the schizophrenics as a group showed an equivalent level of deficit across all test composites, 1) the deficits were associated with different aspects of psychiatric symptomatology, 2) the motor deficit was independent of the cognitive deficits, and 3) each neuropsychological domain contributed independently to the deficit pattern. Thus, what appears to be a generalized functional deficit in schizophrenia may actually be, at least in part, combinations of multiple specific deficits.


Influence of abnormal screens on delays and prognostic indicators of screen-detected breast carcinoma.
Delay to diagnosis following an abnormal screening result is associated with morbidity such as anxiety, but its effect on prognosis is unknown. Using data from the Somme area breast cancer screening programme (France), we identified 29,511 women aged 50-69 years who underwent screening between 1996 and 2000. We prospectively followed women with an abnormal screening result until completion of the assessment process and evaluated the effect of delay to notification, diagnosis and treatment on prognostic indicators. Women with high-suspicion screens (n=976) compared with those with intermediate-suspicion screens (n=1008) were investigated more promptly, presented larger tumours (62% vs 42%, p=0.03), and were more likely to be lymph node positive (36% vs 17%, p=0.02). Compared with a delay to diagnosis </=1 month, the odds ratio for tumour size greater than 10 mm was 1.4 (95% confidence interval[CI], 0.90-1.90) for a delay of 1 to </=6 months, and 1.8 (95% CI, 1.02-2.85) for a delay >6 months. Similarly, a 1.4-fold and 2-fold increased risk of lymph node involvement was observed for delays of >3 to </=6 months and >6 months, respectively, compared with the reference interval. The authors' findings suggest that women with high-suspicion mammograms were investigated more promptly, and that delays to diagnosis of asymptomatic breast carcinoma >6 months were associated with progression of the cancer measured by tumour size >10 mm and lymph node metastasis.


The ventral lateral thalamic nucleus in the dog: cytoarchitecture, acetylthiocholinesterase histochemistry, and cerebellar afferents.
The canine ventral lateral nucleus was defined on the basis of Nissl cytoarchitecture, acetylthiocholinesterase (AChE) chemoarchitecture, and the distribution of cerebellar afferents. It consists of at least two subdivisions: a dorsal and rostral division (VLd) that stains intensely for AChE and contains densely packed cells, and a larger principal division (VL), located ventrocaudally, that stains moderately for AChE and contains a mixture of cells with moderate packing density. Results from autoradiographic, silver degeneration, and AChE material indicate that both divisions receive input from the deep cerebellar nuclei.


Flow cytometry-assisted quantification of γH2AX expression has potential as a rapid high-throughput biodosimetry tool.
Large-scale radiological events require immediate and accurate estimates of doses received by victims, and possibly the first responders, to assist in treatment decisions. Although there are numerous efforts worldwide to develop biodosimetric tools to adequately handle triage needs during radiological incidents, such endeavours do not seem to actively involve sub-Saharan Africa which currently has a significant level of nuclear-related activity. To initiate a similar interest in Africa, ex vivo radiation-induced γH2AX expression in peripheral blood lymphocytes from fourteen healthy donors was assessed using flow cytometry. While the technique shows potential for use as a rapid high-throughput biodosimetric tool for radiation absorbed doses up to 5 Gy, significant inter-individual differences in γH2AX expression emerged. Also, female donors exhibited higher levels of γH2AX expression than their male counterparts. To address these shortcomings, gender-based in-house dose-response curves for γH2AX induction in lymphocytes 2, 4, and 6 h after X-ray irradiation are proposed for the South African population. The obtained results show that γH2AX is a good candidate biomarker for biodosimetry, but might need some refinement and validation through further studies involving a larger cohort of donors.


Shooting through windscreens: ballistic injury assessment using a surrogate head model-two case reports.
A synthetic head model developed to reproduce military injuries was assessed in two different scenarios involving shooting through intermediate targets (a laminated vehicle windscreen in scenario 1 and a military helicopter windscreen in scenario 2) with 7.62 × 39-mm mild steel core (MSC) ammunition. The injury patterns resulting from the two scenarios were assessed by a military radiologist and a forensic pathologist with combat injury experience and found to be clinically realistic.


Self-diffusion and structural properties of confined fluids in dynamic coexistence.
Self-diffusion and radial distribution functions are studied in a strongly confined Lennard-Jones fluid. Surprisingly, in the solid-liquid phase transition region, where the system exhibits dynamic coexistence, the self-diffusion constants are shown to present up to three-fold variations from solid to liquid phases at fixed temperature, while the radial distribution function corresponding to both the liquid and the solid phases are essentially indistinguishable.


A 'Swinging Cradle' model for in vitro classification of different types of response elements of a nuclear receptor.
Nuclear receptors are hormone-activated transcription factors that bind to specific target sequences termed hormone-response element (HRE). A HRE usually consists of two half-sites (5'-AGGTCA-3' consensus sequence) arranged as a direct, everted or inverted repeat with variable spacer region. Assignment of a HRE as a direct, everted or inverted repeat is based on its homology to the consensus half-site, but minor variations can make such an assignment confusing. We hypothesize a 'Swinging Cradle' model for HRE classification, whereby the core HRE functions as the "sitting platform" for the NR, and the extra nucleotides at either end act as the "sling" of the Cradle. We show that in vitro binding of the thyroid hormone receptor and 9-cis retinoic acid receptor heterodimer to an everted repeat TRE follows the 'Swinging Cradle' model, whereas the other TREs do not. We also show that among these TREs, the everted repeat mediates the highest biological activity.


Hierarchical patterns of three-dimensional block-copolymer films formed by electrohydrodynamic jet printing and self-assembly.
Self-assembly of block-copolymers provides a route to the fabrication of small (size, <50 nm) and dense (pitch, <100 nm) features with an accuracy that approaches even the demanding specifications for nanomanufacturing set by the semiconductor industry. A key requirement for practical applications, however, is a rapid, high-resolution method for patterning block-copolymers with different molecular weights and compositions across a wafer surface, with complex geometries and diverse feature sizes. Here we demonstrate that an ultrahigh-resolution jet printing technique that exploits electrohydrodynamic effects can pattern large areas with block-copolymers based on poly(styrene-block-methyl methacrylate) with various molecular weights and compositions. The printed geometries have diameters and linewidths in the sub-500 nm range, line edge roughness as small as ∼45 nm, and thickness uniformity and repeatability that can approach molecular length scales (∼2 nm). Upon thermal annealing on bare, or chemically or topographically structured substrates, such printed patterns yield nanodomains of block-copolymers with well-defined sizes, periodicities and morphologies, in overall layouts that span dimensions from the scale of nanometres (with sizes continuously tunable between 13 nm and 20 nm) to centimetres. As well as its engineering relevance, this methodology enables systematic studies of unusual behaviours of block-copolymers in geometrically confined films.


Physical activity, sugar-sweetened beverages, whole grain bread and insomnia among adolescents and psychological distress in adulthood: prospective data from the population-based HUNT study.
In this study, we examined the relationship between low levels of physical activity, high consumption of sugar-sweetened beverages and low consumption of whole grain bread and experiencing insomnia in adolescence and psychological distress in young adults. This prospective study was based on information retrieved from the Trøndelag Health Study (HUNT) in Norway and included adolescents (age 13-19) participating in Young-HUNT3 (2006-2008) and in HUNT4 (2017-2019) 11 years later (age 23-31). The study sample consisted of 2,230 participants (1,287 females and 943 males). The exposure variables collected in adolescence included self-reported physical activity, consumption of sugar-sweetened beverages and whole grain bread and insomnia, and psychological distress in young adulthood was used as an outcome variable. The relationship between lifestyle behaviours in adolescence and psychological distress in young adulthood was examined using multivariable logistic regression, adjusted for gender, age and psychological distress in adolescence and educational level in young adulthood. An increased odds of psychological distress was shown among young adults who reported low levels of physical activity (OR: 1.44, 95 % CI: 1.10-2.89), high consumption of sugar-sweetened beverages (OR: 1.49, 95 % CI: 1.12-1.98), low consumption of whole grain bread (OR: 1.35, 95 % CI: 1.04-1.77) and insomnia (OR: 1.69, 95 % CI: 1.23-2.33) in adolescence. In terms of absolute differences, unhealthy lifestyle behaviours increased the risk of psychological distress in young adulthood between 3.18 (95 % CI: 0.29-6.07) (low whole grain bread consumption) and 6.01 (95 % CI: 1.95-10.07) (insomnia) percentage points. Low levels of physical activity, high consumption of sugar-sweetened beverages and low consumption of whole grain bread and insomnia during adolescence were associated with psychological distress in young adulthood.


Differences in the basilar artery bifurcation angle among patients who present with a ruptured aneurysm at the top of the basilar artery and patients with perimesencephalic subarachnoid hemorrhage: a retrospective cross-sectional study.
The angle of the basilar artery bifurcation of (BAB angle) is thought to influence the risk of the development and rupture of aneurysms at this site. It is, however, unknown whether the BAB angle also influences the incidence of angiographically negative perimesencephalic subarachnoid hemorrhage (PMSAH). We performed a retrospective cross-sectional study comparing the BAB angle in a series of patients who presented with subarachnoid hemorrhage from a ruptured aneurysm at the top of the basilar artery (BSAH) with the BAB angle in a series of patients who presented with PMSAH. Consecutive patients who presented to our institution with PMSAH or BSAH between January 1, 2005 and December 31, 2010 were studied. Patients with PMSAH were further subdivided into patients with classic PMSAH (CPMSAH) and those with nonclassic PMSAH (NCPMSAH) based on initial head computed tomography examinations. In each patient, the BAB angle was measured on the standard cranial anteroposterior projections after vertebral artery injections. A total of 21 patients with CPMSAH, 30 patients with NCPMSAH, and 31 patients with BSAH were studied. The BAB angle was significantly smaller in patients with CPMSAH (87.7 ± 17.1 degrees) and NCPMSAH (98.4 ± 21.1 degrees) compared with patients with BSAH (135.0 ± 30.8 degrees) (P < .001). The significantly lower BAB angle in PMSAH patients compared with BSAH patients suggests that bleeding in PMSAH is either nonarterial in nature or is secondary to variations in hemodynamic arterial stress at the top of the basilar artery that need to be studied further with computational models.


Interaction of woodchuck hepatitis virus surface antigen with hepatocyte plasma membrane in woodchuck chronic hepatitis.
The extent of association between woodchuck hepatitis virus surface antigen and host hepatocyte plasma membrane in chronic hepatitis was studied. Purified membranes containing the antigen were treated with various agents which perturb plasma membrane constituents to elute woodchuck hepatitis virus surface antigen. The products from disrupted membranes were analyzed by sedimentation in sucrose gradients and tested to identify the antigen reactivity. The results indicated that membrane-bound woodchuck hepatitis virus surface antigen was partially released by 4 M potassium chloride, potassium thiocyanate and guanidine, 6 M urea or 0.1 N sodium hydroxide (pH 13.5), but not in the presence of low concentrations of these reagents or by 10% 2-mercaptoethanol and 1% sodium dodecyl sulfate. No more than 15% of the total membrane-associated woodchuck hepatitis virus surface antigen was eluted by 0.1 N NaOH, which was found to be the most effective eluent among tested agents at the antigen removal. The remaining woodchuck hepatitis virus surface antigen was resistant to further extraction with sodium hydroxide, as expected for an integral membrane protein. Treatment of the infected membranes with 1% Triton X-100 or 50 mM deoxycholic acid, that solubilize the membrane lipid bilayer releasing most of the integral membrane proteins, resulted in the sedimentation of almost all detectable woodchuck hepatitis virus surface antigen reactivity with the detergent-insoluble membrane residues, suggesting a firm interaction of the antigen with the plasma membrane matrix.(ABSTRACT TRUNCATED AT 250 WORDS)


Germ cell tumors of the testis.
Testicular cancer is the most common malignancy in men aged 20 to 35 years and accounts for approximately 1% of all male malignancies. Through the appropriate utilization of clinical trials, effective treatment paradigms have been developed for the management of all stages of testicular cancer. The multidisciplinary approach to the management of germ cell tumors of the testis has resulted in survival rates of > 90% overall. This review summarizes the principal management of germ cell tumors of the testis, highlighting the indications for surgery, controversies surrounding the integration of surgery, and alternative management strategies.


[Management of postoperative intestinal fistulas with elemental diet (author's transl)].
From 1973-1976 sixteen patients with clinically manifest post-operative fistulas (7 small intestinal and 9 colonic) were studied. These patients received an elemental diet (ED) as their only nutritional support for 9-44 days. On ED spontaneous closure was observed in 4 out of 7 small intestinal fistulas and in 7 out of 9 colonic fistulas. Hemoglobin and serum albumin increased significantly on ED and nitrogen balance performed on 7 patients was in equilibrium or positive. Advantages of ED over intravenous nutrition in the treatment of intestinal fistulas are discussed.


Selective inhibition of divergent seryl-tRNA synthetases by serine analogues.
Seryl-tRNA synthetases (SerRSs) fall into two distinct evolutionary groups of enzymes, bacterial and methanogenic. These two types of SerRSs display only minimal sequence similarity, primarily within the class II conserved motifs, and possess distinct modes of tRNA(Ser) recognition. In order to determine whether the two types of SerRSs also differ in their recognition of the serine substrate, we compared the sensitivity of the representative methanogenic and bacterial-type SerRSs to serine hydroxamate and two previously unidentified inhibitors, serinamide and serine methyl ester. Our kinetic data showed selective inhibition of the methanogenic SerRS by serinamide, suggesting a lack of mechanistic uniformity in serine recognition between the evolutionarily distinct SerRSs.


Ventricular contraction and relaxation rates during muscle metaboreflex activation in heart failure: are they coupled?
What is the central question of this study? Does the muscle metaboreflex affect the ratio of left ventricular contraction/relaxation rates and does heart failure impact this relationship. What is the main finding and its importance? The effect of muscle metaboreflex activation on the ventricular relaxation rate was significantly attenuated in heart failure. Heart failure attenuates the exercise and muscle metaboreflex-induced changes in the contraction/relaxation ratio. In heart failure, the reduced ability to raise cardiac output during muscle metaboreflex activation may not solely be due to attenuation of ventricular contraction but also alterations in ventricular relaxation and diastolic function. The relationship between contraction and relaxation rates of the left ventricle varies with exercise. In in vitro models, this ratio was shown to be relatively unaltered by changes in sarcomere length, frequency of stimulation, and β-adrenergic stimulation. We investigated whether the ratio of contraction to relaxation rate is maintained in the whole heart during exercise and muscle metaboreflex activation and whether heart failure alters these relationships. We observed that in healthy subjects the ratio of contraction to relaxation increases from rest to exercise as a result of a higher increase in contraction relative to relaxation. During muscle metaboreflex activation the ratio of contraction to relaxation is significantly reduced towards 1.0 due to a large increase in relaxation rate matching contraction rate. In heart failure, contraction and relaxation rates are significantly reduced, and increases during exercise are attenuated. A significant increase in the ratio was observed from rest to exercise although baseline ratio values were significantly reduced close to 1.0 when compared to healthy subjects. There was no significant change observed between exercise and muscle metaboreflex activation nor was the ratio during muscle metaboreflex activation significantly different between heart failure and control. We conclude that heart failure reduces the muscle metaboreflex gain and contraction and relaxation rates. Furthermore, we observed that the ratio of the contraction and relaxation rates during muscle metaboreflex activation is not significantly different between control and heart failure, but significant changes in the ratio in healthy subjects due to increased relaxation rate were abolished in heart failure.


O-acetylserine (thiol) lyase activity in Phragmites and Typha plants under cadmium and NaCl stress conditions and the involvement of ABA in the stress response.
The roles of O-acetylserine (thiol) lyase (OASTL, EC 184.108.40.206) and abscisic (ABA) acid in stress responses to NaCl and cadmium treatments were investigated in Typha latifolia L. and Phragmites australis (Cav.) Trin. ex Steudel plants. OASTL activity increased under stress (25-300 microM Cd, 100mM NaCl, 1 microM ABA) in both Typha and Phragmites mainly in roots, contributing substantially to satisfy the higher demand of cysteine for adaptation and protection. The earliest significant responses in intact roots were recorded after 12-24 h of Cd treatments, but different levels of stimulation were also observed after 3 and 7 days of exposure. The OASTL activity responses of Phragmites to salinity (100mM NaCl) were higher than those of Typha. Cysteine synthesis in Typha is much higher than in Phragmites, which supports the efficiency of the thiol-metabolism-based protection shown in Typha. Exogenous ABA increased OASTL activity in both species. Cd treatments led to increased ABA levels in roots. Phragmites showed higher ABA levels compared to Typha. The increase of ABA content indicates the involvement of this phytohormone in early stress responses, while the stimulation of OASTL following the ABA application suggests that ABA has a role in an OASTL activation pathway.


Case Report: Recurrent Pyometra in an Adolescent.
Pyometra is an uncommon but serious condition that is generally diagnosed in postmenopausal women. It rarely occurs in premenopausal patients, particularly adolescents. A 16-year-old girl with multiple comorbidities including severe intellectual disability, neurogenic bladder, and recurrent urinary tract infection presented with fever, abdominal pain, and vaginal discharge after prolonged treatment with depot medroxyprogesterone acetate. Ultrasound imaging showed an intrauterine fluid collection consistent with hematometra; however, hysteroscopic evaluation confirmed pyometra, which was evacuated using a suction curette. Despite postoperative antibiotic therapy, she re-presented with similar findings requiring additional hysteroscopic evaluation and evacuation. After a third evacuation, an intrauterine catheter was placed to aid in drainage. This was not tolerated by the patient, and she ultimately required total laparoscopic hysterectomy for definitive management, which was performed without incident. Pyometra is a rare occurrence that typically presents after menopause; however, it should be considered in patients with poor genitourinary hygiene and medically induced endometrial atrophy. In severe cases, hysterectomy might be required for definitive management.


Appraisal of surgical treatment for pulmonary metastasis from hepatocellular carcinoma.
The outcome of pulmonary metastasectomy of hepatocellular carcinoma (HCC) was appraised in this study. Twenty patients with pulmonary metastasis from HCCs undergoing pulmonary resection between 1990 and 2003 were included in this study. They had undergone curative treatment for the primary lesion and were candidates for a pulmonary metastasectomy for complete resection. Among the 20 patients, 13 died: 5 from hepatic failure, 5 from respiratory failure, and 2 from brain metastasis due to recurrence of the HCC. One patient died from cardiac failure without HCC recurrence. At the latest observation, three of the seven survivors were doing well without HCC recurrence, and others survived with recurrence. The overall survival rates after the initial lung surgery were 45.3% at 1 year and 23.8% at 3 years, respectively. The survival rates without recurrence were 32.4% at 1 year and 21.6% at 3 years, respectively. A Kaplan-Meier analysis showed that multiple lung surgeries and a negative histologic finding of the liver cut surface were favorable characteristics for survival without recurrence. In conclusion, the selected patients were Candidates for pulmonary metastasectomy after a curative hepatectomy for HCC and could benefit from the complete resection. Also, repeated pulmonary resections through thoracoscopy could result in the long-term survival of patients with pulmonary recurrence of HCC.


Bilateral posterior choanal atresia: a morphologic and histologic study, and computed tomographic correlation.
Bilateral posterior choanal atresia is an uncommon cause of respiratory obstruction in the newborn. Although the clinical syndrome and treatment options are well known, the abnormal histology has not been well described. Computed tomography (CT) is a useful tool in the radiologic diagnosis of choanal atresia, but has not been correlated with the histopathology. Two patients with CHARGE association (congenital heart defects, choanal atresia, retarded growth and development, hypogenitalism, and aural anomalies) and bilateral posterior choanal atresia were studied with CT. The atresia plates were removed at autopsy and sectioned in an axial plane for gross and microscopic study. The histopathology is described and correlated with the CT studies. These studies show that CT accurately defines the histopathologic abnormalities found in bilateral posterior choanal atresia.


1H NMR spectrum of the native human insulin monomer. Evidence for conformational differences between the monomer and aggregated forms.
The effects of high dilution on the 1H Fourier transform NMR spectrum of native human insulin at pH* 8.0 and 9.3 have been examined at 500 MHz resolution. The dependence of the spectrum on concentration and comparison with the spectrum of a biologically highly potent monomeric insulin mutant (SerB9----Asp) establish that at 36 microM (pH* 9.3) or 18 microM (pH* 8) and no added buffer or salts, human insulin is monomeric. Under these conditions of dilution, ionic strength, and pH*, human insulin and the SerB9----Asp mutant exhibit nearly identical 1H NMR spectra. At higher concentrations (i.e. greater than 36 microM to 0.91 mM), native human insulin dimerizes, and this aggregation causes a change in insulin conformation. Although there are many changes in the spectrum, the TyrB26 ring H3,5 proton signals located at 6.63 ppm and the methyl signal located at 0.105 ppm (characteristics of monomeric insulin) are particularly distinct signatures of the conformation change that accompanies dimerization. Magnetization transfer experiments show that the 0.105 ppm methyl signal shifts downfield to a new position at 0.45 ppm. We conclude that the 0.105 ppm methyl signal is due to a conformation in which a Leu methyl group is centered over and in van der Waals contact with the ring of an aromatic side chain. Dimerization causes a conformation change that alters this interaction, thereby causing the downfield shift. Nuclear Overhauser studies indicate that the methyl group involved is located within a cluster of aromatic side chains and that the closest ring-methyl group interaction is with the ring of PheB24.


Neuroimmune intercommunication, central opioids, and the immune response to bacterial endotoxin.
Muramyl dipeptide is the smallest biologically active fragment of the lipopolysaccharide (LPS) moiety of gram-negative bacteria cell walls. The present report demonstrates that this product, associated with the immune response to bacterial infection, can modify CNS activity. Specifically, it is demonstrated that 6-0-stearoyl-muramyl dipeptide (MDP) can attenuate opiate withdrawal severity in a dose-dependent fashion when injected directly into areas of the brain essential for this phenomenon. In addition, MDP alters both baseline and postnarcotic electrophysiologic responses of four brain areas essential for various opioid activities. Similar findings have been reported for interferon-alpha (IFN-alpha), a peptide associated with the immune response to virus. Yet, even though MDP and IFN are shown to exert similar effects on opioid activity, there are also some very distinct differences in the actions of both of these immune response products. These observations suggest that central opioid systems may provide targets for the perception as well as the differentiation of afferent immunologic sensory input to the brain.


"Act in Time to Heart Attack Signs" action plan: a patient-based critical pathway.
"Act in Time to Heart Attack Signs" provides various educational materials for health care providers, heart attack patients, and the public. These include a booklet, an educational video, and new Web pages, which can be reached through the National Heart, Lung, and Blood Institute website: http://www.nhlbi.nih.gov/actintime.


Risk factors for complications following immediate tissue expander based breast reconstruction in Taiwanese population.
Breast cancer patients in Asia show considerable disparities from Caucasian patients, such as younger age of onset and lower rates of smoking, obesity, and diabetes. Findings of prior studies regarding risk factors associated with complications in tissue expander may not hold for Asian populations, since most of these studies involved Caucasian patients. In this study, we surveyed risk factors in the Taiwanese population, providing additional evidence about the important differences and discuss the implications for clinical practice. Patients who underwent immediate, two-stage, tissue expander breast reconstruction from December 2008 to August 2014 in the National Taiwan University Hospital, Taipei, Taiwan were included. Follow-up observations of all patients were conducted until December 2014. Complications occurring during the tissue expander stage were evaluated. Multivariate regression modeling was used to identify risk factors for complications. A total of 246 consecutive, immediate, smooth round tissue expander placements were performed for breast reconstruction. The most common complication was skin necrosis (4.9%), followed by wound dehiscence (4.1%). In the multivariate model, body mass index (BMI) ≥ 24 kg/m2 was the only risk factor that reached statistical significance (odds ratio: 2.41, 95% confidence interval: 1.17-4.96). We provided evidence that racial disparities have an impact on the risk factors for complications associated with tissue expander breast reconstruction. BMI≥24 kg/m2 was the only risk factor significantly associated with complications. Clinically, BMI≥24 kg/m2, rather than the standard definition of obesity (BMI > 30 kg/m2), may be a more suitable cutoff point for risk in patients of Asian ethnicity.


Solution nuclear magnetic resonance spectroscopy techniques for probing intermolecular interactions.
Nuclear magnetic resonance (NMR) spectroscopy in solution has evolved into a powerful technique for structure determination of proteins and nucleic acids. More recently, a number of NMR-based approaches have been developed to monitor and characterize intermolecular interactions. These approaches offer unique advantages over other techniques and find their utility in both structural biology and drug discovery. We will report on basic principles and recent examples of the application of such NMR methodologies to characterize protein-protein interactions and for ligand binding studies and drug discovery.


Subchronic MK-801 treatment during adolescence induces long-term, not permanent, excitatory-inhibitory imbalance in the rat hippocampus.
Adolescence is a critical neurodevelopmental period for both excitatory and inhibitory (E/I) neurotransmission and often witnesses the typical onsets of schizophrenia. One possibility is that disruptions in adolescent neurodevelopmental processes may produce schizophrenia-like behavioral and neurobiological abnormalities. We previously reported that subchronic treatment of adolescent animals with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 induced cognitive deficits and reduced interneuron densities in rat medial prefrontal cortex, and these changes persisted one week after MK-801 exposure. However, it remains unclear how this treatment may affect E/I balance in hippocampus, which has long been associated with the pathophysiology of schizophrenia. Here, we examined hippocampal E/I biomarkers in adolescent rats treated with MK-801 (0.2 mg/kg, i.p., 14 days) and found increases in the ratio of the expression levels of vesicular glutamate transporter-1 (VGluT1) and vesicular gamma-aminobutyric acid (GABA) transporter (VGAT) 24 h and 7 days after MK-801 exposure. Interestingly, the increased VGluT1/VGAT ratio at the two time points was driven by upregulated VGluT1 expression and downregulated VGAT expression, respectively. The decrease in VGAT expression persisted 14 days after MK-801 exposure and recovered two weeks later. No alterations in hippocampal interneuron densities were observed. Behaviorally, the treatment decreased prepulse inhibition at 24 h but not 14 days, after MK-801 exposure. Taken together, these results demonstrate that subchronic NMDA receptor blockade during adolescence induces long-term, but not permanent, E/I imbalance in the rat hippocampus, which could be attributed to the dysregulation of glutamatergic transmission in the short term and of GABAergic transmission in the long term.


Prenatal screening for preeclampsia: the roles of placental growth factor and pregnancy-associated plasma protein A in the first trimester and placental growth factor and soluble fms-like tyrosine kinase 1-placental growth factor ratio in the early second trimester.
Professional societies have recommended universal first trimester screening for preeclampsia and a second or third trimester soluble fms-like tyrosine kinase-1-placental growth factor ratio test to assess for preeclampsia and its severity. However, it may not be feasible to implement the most optimal screening protocol for preeclampsia in the first trimester which uses a combination of maternal characteristics, maternal biophysical and biochemical markers due to limitations in the access to uterine artery doppler ultrasound. There are inconsistent findings on how early in the second trimester the fms-like tyrosine kinase-1-placental growth factor ratio begins to provide useful information in preeclampsia prediction. This study aimed to assess the accuracy of (1) a combination of maternal characteristics, maternal serum pregnancy-associated plasma protein A, and placental growth factor in the screening for preeclampsia in the first trimester; and (2) placental growth factor or soluble fms-like tyrosine kinase-1-placental growth factor ratio in the prediction of preeclampsia in the early second trimester. This retrospective case-control study used frozen residual blood samples from women who had aneuploidy screening and delivered at a tertiary center. The case group included pregnancies with gestational hypertension or preeclampsia (further classified as early-onset [birth at <34 weeks' gestation] and preterm preeclampsia [birth at <37 weeks' gestation]). Each case was matched with 3 control pregnancies by date of blood sample draw, gestational age at first blood sample draw, maternal age, maternal ethnicity, type of multiple-marker screening, and amount of residual sample. Mann-Whitney U tests were used to assess the associations between serum markers and the risk of preeclampsia. Logistic regressions were used to assess if the risk of preeclampsia can be predicted using a combination of maternal characteristics and serum markers. The case group included 146 preeclampsia and 295 gestational hypertension cases. Compared with the controls, preeclampsia cases had significantly lower first-trimester pregnancy-associated plasma protein A and placental growth factor. At a 20% false-positive rate, 71% of early-onset and 58% of preterm preeclampsia cases can be predicted using maternal characteristics, pregnancy-associated plasma protein A, and placental growth factor. Preeclampsia cases had lower second-trimester placental growth factor and a higher soluble fms-like tyrosine kinase-1-placental growth factor ratio. At a 10% false-positive rate, 80% and 53% of early-onset preeclampsia can be predicted using maternal characteristics and placental growth factor or soluble fms-like tyrosine kinase-1-placental growth factor ratio, respectively. The current first-trimester aneuploidy screening programs may be expanded to identify women at increased risk of developing preeclampsia. Early in the second trimester, placental growth factor alone provided better prediction for preeclampsia compared with the soluble fms-like tyrosine kinase-1-placental growth factor ratio.


Physiology and pathophysiology of androgen action.
Knowledge of the physiology of male sexual differentiation and the clinical presentation of androgen insensitivity syndromes (AIS) has led to an increasing understanding of the mechanisms of androgen action. Androgens induce their specific response via the androgen receptor (AR), which in turn regulates the transcription of androgen-responsive target genes. The androgen-dependent development of male genital structures and the induction of the normal male phenotype depends on the presence of an intact AR. Structural alterations leading to malfunction of the AR are associated with variable inhibition of virilization despite normal or even supranormal serum levels of androgens. The mapping, cloning and sequencing of the AR gene have facilitated new insights into the study of androgen action. Functional investigation of the normal and the mutant AR in vivo as well as in vitro has led to the characterization of the distinct molecular steps involved in the normal androgen action pathways that are inhibited in the androgen insensitivity syndrome.


Effect of exogenous prostaglandin E2 and actinomycin D on plasma leakage induced by neutrophil-activating peptide-1/interleukin-8.
Neutrophil accumulation and plasma leakage were measured in rabbit skin at sites stimulated with recombinant human neutrophil activating peptide-1/interleukin-8 (NAP-1/IL-8). Neutrophil accumulation occurred at doses equal to or greater than 10(-11) moles NAP-1/IL-8 per site. Co-injection of prostaglandin E2 (PGE2) extended the threshold of inflammatory activity of NAP-1/IL-8 to less than 10(-13) moles/site and caused approximately three-fold increases in neutrophil accumulation and ten-fold increases in plasma leakage at the higher doses of NAP-1/IL-8 examined. Plasma leakage declined more rapidly than did neutrophil accumulation as lesions aged. It was postulated that an endothelial response may be initiated to limit plasma leakage during ongoing neutrophil emigration at sites stimulated with NAP-1/IL-8. The induction of vasodilatation by injection of PGE2 masked the decline of plasma leakage with time in lesions up to 120 min old. Co-injection of the RNA synthesis inhibitor, actinomycin D, failed to abrogate the decline of plasma leakage with time, suggesting that de novo protein synthetic events such as production of the vasoconstrictor peptide, endothelin, are unlikely to contribute to the mechanism that restricts plasma leakage in older lesions. Although plasma leakage induced by NAP-1/IL-8 is dependent on the emigration of neutrophils, the results indicate that a mechanism, independent of de novo protein synthesis, restricts the rate of plasma leakage per neutrophil as lesions age.


A simple behavioral paradigm for the study of type I hippocampal rhythmical slow activity (RSA) frequency shifts.
A simple behavioral paradigm is described in which hippocampal electroencephalographic (EEG) rhythmical slow activity (RSA) frequency shifts can be correlated with other central or behavioral events. Rabbits placed in various postures right spontaneously in a relatively stereotyped way. The movements are associated with RSA frequency shifts and the highest RSA frequencies occur when rabbits right from an inverted posture. The peak RSA frequency is correlated with rapid heat rotation. Not only does this paradigm provide a simple way of studying RSA frequency correlates, the results obtained in its description suggest that there is a close relation between the speed with which a movement is initiated rather than with the distance that an animal is carried by the movement.


Oxylipin metabolism in response to stress.
Oxylipins comprise a group of biologically active compounds whose structural diversity is generated by the coordinate action of lipases, lipoxygenases, and a group of cytochromes P450 that are specialized for the metabolism of hydroperoxy fatty acids. Research on oxylipins has focused mainly on the biosynthesis of the plant signaling molecule jasmonic acid, and its role in the regulation of developmental and defense-related processes. Recent genetic studies indicate that metabolic precursors of jasmonate are active as signals in their own right, and that the synthesis and perception of jasmonates is critical for wound-induced systemic defense responses. Increasing evidence indicates that the collective biological importance of oxylipins in plants is comparable to that of the eicosanoid family of lipid mediators in animals.


Gold-catalyzed hydration of haloalkynes to α-halomethyl ketones.
A general atom-economical approach for the synthesis of α-halomethyl ketones is demonstrated through hydration of a wide range of haloalkynes. Other outstanding features include excellent yields from both alkyl- and aryl-substituted haloalkynes and wide functional group tolerance. This protocol is an alternative to conventional α-halogenation of ketones.


Improvement of core-fucosylated glycoproteome coverage via alternating HCD and ETD fragmentation.
Core-fucosylation (CF) plays important roles in regulating biological processes in eukaryotes. Alterations of CF-glycosites or CF-glycans in bodily fluids correlate with cancer development. Therefore, global research of protein core-fucosylation with an emphasis on proteomics can explain pathogenic and metastasis mechanisms and aid in the discovery of new potential biomarkers for early clinical diagnosis. In this study, a precise and high throughput method was established to identify CF-glycosites from human plasma. We found that alternating HCD and ETD fragmentation (AHEF) can provide a complementary method to discover CF-glycosites. A total of 407 CF-glycosites among 267 CF-glycoproteins were identified in a mixed sample made from six normal human plasma samples. Among the 407 CF-glycosites, 10 are without the N-X-S/T/C consensus motif, representing 2.5% of the total number identified. All identified CF-glycopeptide results from HCD and ETD fragmentation were filtered with neutral loss peaks and characteristic ions of GlcNAc from HCD spectra, which assured the credibility of the results. This study provides an effective method for CF-glycosites identification and a valuable biomarker reference for clinical research. CF-glycosytion plays an important role in regulating biological processes in eukaryotes. Alterations of the glycosites and attached CF-glycans are frequently observed in various types of cancers. Thus, it is crucial to develop a strategy for mapping human CF-glycosylation. Here, we developed a complementary method via alternating HCD and ETD fragmentation (AHEF) to analyze CF-glycoproteins. This strategy reveals an excellent complementarity of HCD and ETD in the analysis of CF-glycoproteins, and provides a valuable biomarker reference for clinical research.


Synthesis, structure and biological evaluation of ruthenium(III) complexes of triazolopyrimidines with anticancer properties.
Six novel ruthenium(III) complexes of general formula [RuCl3(L)3] (1,3,5) and [RuCl3(H2O)(L)2] (2,4,6), where L stands for three different triazolopyrimidine-derived ligands, are reported. The compounds have been structurally characterized (IR, EPR, SCXRD), and their magnetic moments have been determined. The single-crystal X-ray diffraction study revealed a slightly distorted octahedral geometry of the Ru(III) complexes with mer configuration in 1 and 5, and fac configuration in 3. In 2 and 4, three chloride ions are in mer configuration and the two triazolopyrimidines are oriented trans mutually with the water molecule playing the role of the sixth ligand. All complexes have been thoroughly screened for their in vitro cytotoxicity against human breast cancer cell line MCF-7, human cervical cancer cell line HeLa, and L929 murine fibroblast cells, uncovering among others that the most lipophilic complexes 5 and 6, containing the bulky ligand dptp (5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine), display high cytotoxic activity against MCF-7, and HeLa cells. Moreover, it was also revealed that during the interaction of the complexes 1-6 with the cancer MCF-7 cell line, reactive oxygen species are released intracellularly, which could indicate that they are involved in cell apoptosis. Furthermore, extensive studies have been carried out to reveal the mechanism by which complexes 1-6 interact with DNA, albumin, and apotransferrin. The biological studies were complemented by detailed kinetic studies of the hydrolysis of the complexes in the pH range 5-8, to determine the stability of the complexes in solution. Six novel ruthenium(III) complexes with triazolopyrimidine derivatives demonstrated the potential for use as anticancer agents by maintaining the toxic effect on MCF-7 and HeLa cells.


Crystal structure of di-ammonium bis-[tris-(oxamide dioxime-κ2 N,N')nickel(II)] bis-[tris-(oxalato-κ2 O,O')chromate(III)] 6.76-hydrate.
The asymmetric unit of the title compound, (NH4)2[Ni(C2H6N4O2)3]2[Cr(C2O4)3]2·6.76H2O, comprises two NH4 + cations, two [Ni(C2H6N4O2)3]2+ cations and two [Cr(C2O4)3]3- anions, as well as eight water mol-ecules of crystallization of which only one is fully occupied. In the cationic and anionic complexes, the central atoms (NiII and CrIII) are each surrounded by three bidentate ligands (N-chelating oxamide dioxime and O-chelating oxalate, respectively), resulting in distorted octa-hedral coordination spheres. In the crystal, O-H⋯O hydrogen bonds between the oxamide dioxime ligands as donor groups and the oxalate ligands as acceptor groups alternately connect the cationic and anionic complexes into infinite pillars extending parallel to [100]. Moreover, N-H⋯O hydrogen bonds between the same ligands connect neighboring pillars, thus delineating channels that accommodate the charge-balancing NH4 + cations as well as the water mol-ecules of crystallization. Although the H atoms could not be localized for these two species, the corresponding N⋯O and O⋯O distances indicate hydrogen bonds of medium strength.


Efficacy and Safety of a Surgeon-Performed Laparoscopic-Guided, 4-point Transversus Abdominis Plane Block: A retrospective review.
We performed a retrospective chart review from October 2017 to March 2019 to demonstrate the safety and efficacy of a surgeon-performed, laparoscopically guided, transversus abdominis plane (TAP) blocks for robot-assisted gynecologic procedures. A total of 116 patients who underwent robot-assisted gynecologic surgery, at 1 academic hospital, with administration of a 4-point TAP block were included. A 4-point TAP block was performed under laparoscopic visualization, by the same surgeon, after induction of anesthesia and immediately after placement of the laparoscope. Liposomal bupivacaine (20 mL) and 0.5% bupivacaine (20 mL) mixed with saline were used as the injectant. All information from the surgical admission and the postoperative follow-up were reviewed. Data were presented in our descriptive study. A total of 116 patients were included with a mean age of 40.6 years (19-80 years) and a mean body mass index of 30.6 kg/m2 (17.2-53.3 kg/m2). Of the patients, 70.7% were discharged to home on the day of surgery. Of the 29.3% of patients who were admitted, 20.6% were admitted because of pain control. Those who were admitted for pain control comprised 6.0% of the total of all study participants. There were no adverse events in our cohort and no readmissions because of pain control. A surgeon-performed TAP block, under laparoscopic visualization, is a safe and efficacious intervention to reduce postoperative pain and may add to a multimodal approach for enhanced recovery protocols.


[Clinical evaluation of two kinds homogenous assays for determination of high-density lipoprotein cholesterol].
To evaluate the clinical efficacy of two kinds homogenous assays for direct determination of high-density lipoprotein cholesterol (HDL-C) based on the principle of polyanion polymer/detergent (PPD method) and polyethylene glycol-modified enzyme (PEGME) method. The two homogenous methods were compared with the precipitation method (PTA-Mg2+ method), their precision, accuracy, specificity and interference were also analyzed. Both homogenous HDL-C assays were precise, having a within-run CV < 3%, day-to-day CV < 3% and total CV < 4%. The HDL-C values measured by the two homogenous methods correlated well with those by PTA-Mg2+ method (X): Y = 0.9316 X + 0.1063, r = 0.9762 for PPD method (Y); and Y = 0.9106 X + 0.1368, r = 0.9894 for PEGME method (Y). The linearity studies showed the two homogenous methods to be linear up to 4.14 mmol/L. The lowest detectable concentration of the two methods was apparently 0.08 mmol/L. Recoveries of the two methods were 94.1%-106.2%. Hemoglobin did not interfere with the HDL-C results in the two homogenous methods, whereas icteric samples with total bilirubin > 200 mg/L showed discrepancies. Lipemia up to triglyceride concentration of 17.0 mmol/L did not interfere with the two homogenous HDL-C assays. The two new homogenous HDL-C assays meet the requirements for accuracy, precision, ease of handling with massive sample, allow full automation, and are clinically useful.


Poor adherence to clinical practice guidelines: A call to action for increased albuminuria testing in patients with type 2 diabetes.
We describe the substantial shortfall in adherence to guideline-recommended albumin-to-creatinine ratio (uACR) testing for people in the United States with type 2 diabetes. Poor compliance with current guidelines leads to delays in diagnosis-and treatment- of chronic kidney disease, which adversely affects clinical outcomes and contributes to incremental economic burden.


Effect of chronic somatic diseases on the course of late-life depression.
To examine the influence of specific chronic somatic diseases and overall somatic diseases burden on the course of depression in older persons. This was a prospective cohort study with a 2-year follow-up. Participants were depressed persons (n = 285) from the Netherlands Study of Depression in Older Persons. The presence of chronic somatic diseases was based on self-report. Diagnosis of depression was assessed with the Composite International Diagnostic Interview, and severity of depression was measured with the Inventory of Depressive Symptomatology Self-report. Cardiovascular diseases (odds ratio [OR] = 1.67, 95% confidence interval [CI] = 1.02-2.72, p = 0.041), musculoskeletal diseases (OR = 1.71, 95% CI = 1.04-2.80, p = 0.034), and the number of chronic somatic diseases (OR = 1.37, 95% CI = 1.16-1.63, p < 0.001) were associated with having a depressive disorder at 2-year follow-up. Furthermore, chronic non-specific lung diseases, cardiovascular diseases, musculoskeletal diseases, cancer, or cumulative somatic disease burden were associated with a chronic course of depression. Somatic disease burden is associated with a poor course of late-life depression. The course of late-life depression is particularly unfavorable in the presence of chronic non-specific lung diseases, cardiovascular diseases, musculoskeletal diseases, and cancer. Copyright © 2016 John Wiley & Sons, Ltd.


Failure of cefepime therapy in treatment of Klebsiella pneumoniae bacteremia.
A case of failure of cefepime treatment of a bloodstream infection with AmpC-producing Klebsiella pneumoniae is reported. The failure was attributed to extended-spectrum beta-lactamase (ESBL) acquisition by the isolate, possibly during therapy. Problems encountered with ESBL detection in AmpC-producing isolates are discussed.


The influence of fentanyl on an alfathesin infusion technique.
The effects of fentanyl (1 microgram/kg) supplementing an alfathesin infusion technique were assessed in a double blind study in 53 healthy unpremedicated female patients undergoing therapeutic abortion as outpatients. The addition of fentanyl reduced the tachycardia, tachypnoea and hyperventilation seen in those patients receiving alfathesin alone, without unduly prolonging recovery time. Two patients receiving alfathesin alone developed marked coughing or laryngospasm. Fentanyl would seem to be a desirable addition to an alfathesin infusion technique in unpremedicated patients presenting for outpatient anaesthesia.


A summary of important documents in the field of research ethics.
Today's researchers are obligated to conduct their studies ethically. However, it often seems a daunting task to become familiar with the important ethical codes required to do so. The purpose of this article is to examine the content of those ethical documents most relevant to the biomedical researcher. Documents examined include the Nuremberg Code, the Declaration of Helsinki, Henry Beecher's landmark paper, the Belmont Report, the U.S. Common Rule, the Guideline for Good Clinical Practice, and the National Bioethics Advisory Commission's report on research protections for the mentally ill.


Aversion-associated drug and alcohol seeking in females.
Compulsive drug intake is characterized by the continuation of use regardless of negative consequences. This is modeled preclinically using procedures where a negative stimulus is delivered contingently with consumption of the reinforcer. In humans, women and men exhibit different drug taking behavior as it pertains to overall use, withdrawal symptoms, and rate of dependence. In substance use research, females have often been excluded from many studies due to concerns that circulating sex hormones may affect drug seeking behavior. However, the more recent inclusion of females in preclinical studies has identified interesting sex differences in aversion-resistant intake of drugs and alcohol. This review will serve to summarize key findings in aversion-related intake of alcohol, psychostimulants, and opioids in females by examining studies that have included female subjects. Further discussion will examine the effect of intake model, neuroanatomical pathways, and sex hormones in the expression of aversion-resistant drug and alcohol consumption.


Bioaccumulation, oxidative stress and HSP70 expression in Cyprinus carpio L. exposed to microcystin-LR under laboratory conditions.
Microcystin-LR (MC-LR) produced by cyanobacteria are potent specific hepatotoxins. So far the pathogenesis of environmental MC-LR toxicity to aquatic organisms has not been fully elucidated. In the present study the accumulation of MC-LR was investigated in various organs/tissues of Cyprinus carpio L. (C. carpio) following exposure to MC-LR for 14 d at environmentally relevant concentrations (0.1 to 10 μg L(-1)). Results showed that the presence of MC-LR enhanced toxin accumulation in all investigated organs and the highest accumulation was found in the liver of fish exposed to 5.0 μg L(-1) of MC-LR. An EPR analysis indicated ·OH intensity in liver was significantly induced at 0.1 μg L(-1) of MC-LR and then restored when the MC-LR concentration was greater than 0.1 μg L(-1). After 14-day exposure, MC-LR (1.0-10.0 μg L(-1) of MC-LR) caused a pronounced promotion of glutathione S-transferase (GST) activity and a depletion of reduced glutathione (GSH) content in fish liver, which indicated that GSH was involved in detoxification of MC-LR and the conjugation reaction of MC-LR and GSH occurred. A mild oxidative damage was evidenced by the accumulation of malondialdehyde (MDA) level at 5.0 μg L(-1) of MC-LR exposure, but which was restored when the MC-LR concentration was increased to 10.0 μg L(-1). The responses of antioxidant enzymes and the induction of HSP70 expression might contribute to MC-LR tolerance of C. carpio. However, the protein phosphatase (PP) activities were strikingly inhibited in all treated groups. Thus, the overall toxicity of environmental MC-LR on C. carpio seems to be initiated in the liver via both the ROS pathway and the PP inhibition pathway, and the latter might be more important when ambient MC-LR concentration is greater than 0.1 μg L(-1). More importantly, these results can help to support the evaluation on the potential effects of MC-LR under common environmental concentrations.


Diagnosis and management of urinary tract infections in children aged 2 months to 3 years in the Italian emergency units: the ItaUTI study.
Urinary tract infections (UTIs) are among the most frequent bacterial diseases in infants and children. Physician adherence to recommendations is notoriously often poor, but no data are available on UTIs management in the emergency setting. In this multicenter national study, we investigated the policies regarding UTIs management in children aged 2 months to 3 years in Italian emergency units. Between April and June 2021, directors of the emergency units were invited to answer an online survey on the following items: diagnostic approach to children with fever without an apparent source, therapeutic approach to UTIs, the use of kidney and urinary tract ultrasound, and the criteria for hospitalization. A total of 121 (89%) out of 139 of invited units participated in the study. Overall, units manage children with a suspected or confirmed UTI according to available recommendations for most of the items. However, in almost 80% (n = 94) of units, a sterile perineal bag is used to collect urine for culture. When urine is collected by cathether, heterogeneity exists on the threshold of bacterial load considered for UTI diagnosis. Conclusions: Available recommendations on UTIs in children are followed by Italian emergency units for most of the items. However, the methods to collect urine specimens for culture, one of the crucial steps of the diagnostic work-up, often do not align with current recommendations and CFU thresholds considered for diagnosis largely vary among centers. Efforts should be addressed to validate and implement new child and family friendly urine collection techniques. What is Known: • Several guidelines are published on the management of children with suspected or confirmed urinary tract infection. • No data are available on the management of pediatric urinary tract infections in the emergency setting. What is New: • Almost 80% of the Italian emergency units employ a sterile perineal bag to collect urine for culture. • Diagnostic CFU thresholds largely vary among centers.


Protective effects of 7-nitroindazole on ketamine-induced neurotoxicity in rat forebrain culture.
Ketamine, a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, is used as a pediatric anesthetic for surgical procedures. Recent data suggest that anesthetic drugs may cause neurodegeneration during development. The purpose of this study was to determine the dose and temporal response of ketamine using newborn rat forebrain cultures and also to determine if co-administration of 7-nitroindazole, a nitric oxide synthase (NOS) inhibitor, could protect or reverse ketamine-induced cell death. Neural cells collected from the rat forebrain were incubated for 24h with 1, 10 or 20 microM ketamine alone or with ketamine plus 1, 5, 10 or 20 microM 7-nitroindazole. Ketamine (10 microM) caused an increase in DNA fragmentation and elevated immunoreactivity to nitrotyrosine, a marked reduction in the expression of the neuronal marker polysialic acid neural cell adhesion molecule (PSA-NCAM) and in mitochondrial metabolism, as well as an increased Bax/BCL-XL ratio. No significant effect was observed in the release of lactate dehydrogenase (LDH). Ketamine-induced neurotoxic effects were effectively blocked by 7-nitroindazole (10 microM). These data indicate a role for nitric oxide in the enhanced degeneration induced by ketamine in vitro and also suggest that blocking neuronal nitric oxide synthase (nNOS) may help reduce the risk of ketamine in pediatrics.


First report of deutonymph Myianoetus, Willmann, 1937 (Acari: Astigmata) from Iran.
Myianoetus is a Histiostomatidae mites that are phoretic on flies. The relation between flies and phoretic mites is considered to be of potential value in forensic studies, as the development of flies associated with decomposing human remains. So, they may useful in determining the time of death of an individual. This study represents the first records of Myianoetus muscarum deutonymph phoretic on adult Musca domestica in Iran. Further studies are needed to find any relation between phoretic mites and flies.


Mast cells and transforming growth factor-beta expression: a possible relationship in the development of porphyria cutanea tarda skin lesions.
Porphyria cutanea tarda (PCT) is a metabolic disease characterized by vesicles and blisters in sun-exposed areas and scleroderma-like lesions in sun-exposed and non-sun-exposed areas. Mast cells participate in the pathogenesis of bullous diseases and diseases that show sclerosis, including PCT. Moreover, transforming growth factor-beta (TGF-beta) is the main cytokine in the development of tissue sclerosis. The correlation of mast cells and TGF-beta with the lesions of PCT has not been examined, however. The possible role of mast cells and TGF-beta (and the relationship between them) in the development of PCT lesions is discussed. To quantify mast cells and cells expressing TGF-beta in skin samples from patients with PCT and controls, immunohistochemical studies were performed in tissue sections allied to morphometric analyses. The numbers of mast cells and cells expressing TGF-beta per square millimeter were increased in the PCT group relative to controls, and there was a direct and significant correlation between the mast cell number and cells expressing TGF-beta in PCT. The results suggest that the increased number of mast cells and of cells expressing TGF-beta, as well as their direct correlation, may contribute to the pathogenesis of the skin lesions in PCT.


Systemic effects of surgery: quantitative analysis of circulating basic fibroblast growth factor (bFGF), Vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGF-beta) in patients with breast cancer who underwent limited or extended surgery.
To assess if feature, extent and duration of surgery could influence levels of systemic proangiogenic cytokines vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGF-beta). We collected blood samples from 82 consecutive breast cancer patients who underwent various types of surgery, classified according to the magnitude of tissue injury in: minimal (quadrantectomy), moderate (mastectomy without reconstruction), and heavy [mastectomy followed by reconstruction with transversus recto-abdominal muscle cutaneous flap (TRAM)]. Samples were collected one day before surgery (D(-1)), at the end of surgical tumor removal (D0), and on 1st (D(+1)), 2nd (D(+2)) and 5th (D(+5)) day after surgery. Serum VEGF, bFGF and TGF-beta levels were measured by the enzyme immunoassay method. On average a continuous decrease was observed for all growth factors from the day before operation to the 5th day after operation. On day (D(+5)) an increase was observed for patients who underwent extended respect to moderate surgery. These differences were found statistically significant for bFGF and VEGF (p = 0.05 and p = 0.025 respectively). A statistically different trend for type of operation was observed also for TGF-beta at 24-48 h: a minor reduction, compared to time of operation, was observed for minimal surgery, an intermediate reduction for moderate surgery and a higher decrease for extended surgery. Angiogenic cytokines perioperative levels could be increased on 5th day (D(+5)) by extent of surgery and should induce perioperative stimulation of residual cancer cells. A better understanding of the time interval during which the sequelae of events in wound healing occur may be the basis for defining new therapeutic strategies that can interfere with tumor outgrowth sparing wound healing processes.


A morphological survey of root grooves and their influence on periodontal attachment loss.
Periodontal health reflects a balance between harmful and protective elements in the gingival marginal area. The total plaque mass, specific periodontopathogens, the tooth morphology, and local environmental factors may challenge this balance. The periodontal ligament attachment loss shifts this balance adversely toward the periodontal disease. The aim of this retrospective study was to determine the significance of proximal root grooves as a risk factor in the periodontal attachment loss; the effect of their dimensions and locations has been evaluated. One hundred (100) extracted formalin stored single rooted permanent anterior teeth were studied by staining with 0.1% toludine blue to visualize attached periodontal ligament remnants. On each tooth, the loss of attachment was measured from the cemento-enamel junction to the most coronal level of the stained periodontal ligament remnants. The prevalence of proximal root grooves was found to be 81% and a statistically significant greater loss of attachment was present on grooved than on non-grooved surfaces (p < 0.01). Generally, there was direct relationship between groove location, its dimensions, and maximum loss of attachment. The results suggest that proximal root grooves should be considered in periodontal diagnosis, prognosis, and treatment planning.


Genome-wide association studies revealed complex genetic architecture and breeding perspective of maize ear traits.
Maize (Zea Mays) is one of the world's most important crops. Hybrid maize lines resulted a major improvement in corn production in the previous and current centuries. Understanding the genetic mechanisms of the corn production associated traits greatly facilitate the development of superior hybrid varieties. In this study, four ear traits associated with corn production of Nested Association Mapping (NAM) population were analyzed using a full genetic model, and further, optimal genotype combinations and total genetic effects of current best lines, superior lines, and superior hybrids were predicted for each of the traits at four different locations. The analysis identified 21-34 highly significant SNPs (-log10P > 5), with an estimated total heritability of 37.31-62.34%, while large contributions to variations was due to dominance, dominance-related epistasis, and environmental interaction effects ([Formula: see text] 14.06% ~ 49.28%), indicating these factors contributed significantly to phenotypic variations of the ear traits. Environment-specific genetic effects were also discovered to be crucial for maize ear traits. There were four SNPs found for three ear traits: two for ear length and weight, and two for ear row number and length. Using the Enumeration method and the stepwise tuning technique, optimum multi-locus genotype combinations for superior lines were identified based on the information obtained from GWAS. Predictions of genetic breeding values showed that different genotype combinations in different geographical regions may be better, and hybrid-line variety breeding with homozygote and heterozygote genotype combinations may have a greater potential to improve ear traits.


A multiple mutant of Escherichia coli lacking the exoribonucleases RNase II, RNase D, and RNase BN.
A multiple mutant strain of Escherichia coli containing mutations affecting the exoribonucleases, RNase II, RNase D, and RNase BN, and also the endonuclease, RNase I, was constructed by P1-mediated transduction. Extracts of the mutant strain were lacking the aforementioned RNase activities. The multiple mutant displayed normal growth in both rich and minimal media at a variety of temperatures, recovered from starvation essentially as the wild-type parent, and could support the growth of a variety of bacteriophages. In addition, RNA synthesis was normal and no precursor RNA accumulation was observed. The properties of the mutant strain indicate that the three exoribonucleases are not essential for the viability of E. coli. The implications of these findings to our understanding of RNA processing and degradation are discussed.


Tenofovir alters the immune microenvironment of pregnant women with hepatitis B virus infection: Evidence from single-cell RNA sequencing.
Mother-to-child is the main route of the transmission of hepatitis B virus (HBV) infection. Tenofovir fumarate (TDF) antiviral treatment has become the most extensive choice worldwide. However, the effects of TDF treatment on the immune function of pregnant women remains unclear. Here we investigate the effect of TDF treatment on the immune microenvironment of pregnant women with HBV infection using single-cell RNA sequencing (scRNA-seq). Three HBV-infected pregnant women were treated with TDF and six samples were collected before and after the treatment. In total, 68,200 peripheral blood mononuclear cells (PBMCs) were extracted for 10 × scRNA-seq. The cells were clustered using t-distributed stochastic neighbor embedding (t-SNE) and unbiased computational informatics analysis. The analysis identified four-cell subtypes, including T cells, monocytes, natural killer (NK) cells, and B cells, and unraveled the developmental trajectory and maturation of CD4+ T and CD8+ T cell subtypes. The cellular state and molecular features of the effector/memory T cells revealed a significant increase in the inflammatory state of CD4+ T cells and the cytotoxic characteristics of CD8+ T cells. Additionally, after TDF treatment, the monocytes showed a tendency for M1 polarization, and the cytotoxicity of NK cells was enhanced. Furthermore, the analysis of intercellular communication revealed the interaction of various subtypes of cells and the heterogeneous expression of key signal pathways. The findings of this study reveal significant differences in cellular subtypes and molecular characteristics of PBMCs of pregnant women with HBV infection before and after TDF treatment and demonstrate the recovery of immune response after treatment. These findings could help develop immune intervention measures to control HBV during pregnancy and the puerperium period.


Release of leukotrienes C (LTC) and D (LTD) from inflammatory macrophages during phagocytosis of zymosan and bacteria.
Release of slow-reacting substance (SRS) was obtained from resident mouse peritoneal macrophages (R-M phi) upon stimulation with phagocytic stimuli (zymosan, bacteria). The release of SRS from thioglycollate elicited M phi was impaired, whereas that from BCG-elicited M phi was quantitatively unaffected. However, using a high pressure liquid chromatography separation procedure, qualitative variations between SRS released from R-M phi and BCG-M phi were observed. In both cases, LTC was the major component released from M phi, but greater amounts of LTD were released from BCG-M phi than from R-M phi. These data indicate that local environment alters leukotriene generation by M phi.


[Falling ill as a migrant, psychological and cultural aspects].
When the body fails a person's foundations are damaged. The wait for a diagnosis, the physical pain, the chronic disease weaken the patient who may be overwhelmed by fears and anxiety. For patients from another country, this distressing experience adds to their vulnerability inherent to the separation from the home country the effects of which are intensified when illness strikes.


Acute effects of right ventricular apical pacing on left atrial remodeling and function.
The acute effects of right ventricular apical (RVA) pacing on left atrial (LA) function in patients with normal ejection fraction are not clear. A total of 94 patients (age 68.1 ± 11.1 years, 26 men) with implanted RVA-based dual-chamber pacemakers were recruited into this study. Patients who were pacemaker-dependent, in persistent atrial fibrillation or left ventricular ejection fraction <45% were excluded. Echocardiography (iE33, Philips, Andover, MA, USA) was performed during intrinsic ventricular conduction (V-sense) and RVA pacing (V-pace) with 15 minutes between switching modes. The total maximal LA volume (LAV(max)), preatrial contraction volume (LAV(pre)), and minimal volume (LAV(min)) were assessed by area-length method. Peak systolic, early diastolic, and peak late diastolic (atrial contractile) velocity (Sm-la, Em-la, and Am-la) and strain (ɛs-la, ɛe-la, and ɛa-la) were measured by color-coded tissue Doppler imaging (TDI) in four mid-LA walls at apical four- and two-chamber views. During V-pace, LA volumes increased significantly compared with V-sense (LAV(max): 52.0 ± 18.8 vs 55.2 ± 21.1 mL, P = 0.005; LAV(pre): 39.8 ± 16.4 vs 41.3 ± 16.6 mL, P = 0.014; LAV(min): 27.4 ± 14.0 vs 29.1 ± 15.1 mL, P = 0.001). TDI parameters showed significant reduction in Sm-la and Em-la. Furthermore, ɛs-la, ɛe-la, and ɛa-la decreased significantly, especially in patients with preexisting diastolic dysfunction (all P < 0.01). RVA pacing acutely induced LA enlargement and impaired atrial contractility. Patients with preexisting diastolic dysfunction may be more vulnerable to develop LA dysfunction and remodeling after acute RVA pacing.