Bortezomib therapy response is independent of cytogenetic abnormalities in relapsed/refractory multiple myeloma.
Myeloma patients with unfavorable molecular cytogenetics have a poor prognosis irrespective of treatment with conventional chemotherapy or autologous stem cell transplant. To investigate whether bortezomib, a new proteasome inhibitor, is active in relapsed/refractory myeloma patients with genetic risk factors, we evaluated the outcome of 65 patients and correlated the clinical response with 13q deletion, translocations t(11;14) and t(4;14) and CKS1B amplification as detected by interphase cytoplasmic fluorescence in situ hybridization (cIg-FISH). Thirty-seven of 61 (61%) evaluable patients had an objective response to bortezomib with median progression free (PFS) and overall survivals (OS) of 9.5 and 15.1 months, respectively. Of 43 cases with evaluable bone marrows, cIg-FISH determination of del(13q), t(4;14), t(11;14) and CKS1B amplification was done on 40, 41, 41 and 37 cases and the frequency of their detection was 35%, 15%, 15%, and 32%, respectively. There was no statistically significant difference in response to bortezomib for patients with or without 13q deletion (77% versus 50%), t(4;14) (67% versus 56%), t(11;4) (33% versus 62%), or CKS1B amplification (67% versus 57%). Furthermore, there was no statistically significant difference in PFS or OS following bortezomib therapy between patients with or without these molecular cytogenetic abnormalities. Our data suggest that, in this pilot study, bortezomib is an effective salvage therapy for refractory/relapsed myeloma, irrespective of genetic risk factors.


Processing multiple non-adjacent dependencies: evidence from sequence learning.
Processing non-adjacent dependencies is considered to be one of the hallmarks of human language. Assuming that sequence-learning tasks provide a useful way to tap natural-language-processing mechanisms, we cross-modally combined serial reaction time and artificial-grammar learning paradigms to investigate the processing of multiple nested (A(1)A(2)A(3)B(3)B(2)B(1)) and crossed dependencies (A(1)A(2)A(3)B(1)B(2)B(3)), containing either three or two dependencies. Both reaction times and prediction errors highlighted problems with processing the middle dependency in nested structures (A(1)A(2)A(3)B(3)_B(1)), reminiscent of the 'missing-verb effect' observed in English and French, but not with crossed structures (A(1)A(2)A(3)B(1)_B(3)). Prior linguistic experience did not play a major role: native speakers of German and Dutch-which permit nested and crossed dependencies, respectively-showed a similar pattern of results for sequences with three dependencies. As for sequences with two dependencies, reaction times and prediction errors were similar for both nested and crossed dependencies. The results suggest that constraints on the processing of multiple non-adjacent dependencies are determined by the specific ordering of the non-adjacent dependencies (i.e. nested or crossed), as well as the number of non-adjacent dependencies to be resolved (i.e. two or three). Furthermore, these constraints may not be specific to language but instead derive from limitations on structured sequence learning.


Development and evaluation of a short 24-h food list as part of a blended dietary assessment strategy in large-scale cohort studies.
The validity of dietary assessment in large-scale cohort studies has been questioned. Combining data sources for the estimation of usual intake in a blended approach may enhance the validity of dietary measurement. Our objective was to develop a web-based 24-h food list for Germany to identify foods consumed during the previous 24 h and to evaluate the performance of the new questionnaire in a feasibility study. Available data from the German National Nutrition Survey II were used to develop a finite list of food items. A total of 508 individuals were invited to fill in the 24-h food list via the Internet up to three times during a 3-6-month time period. In addition, participants were asked to evaluate the questionnaire using a brief online evaluation form. In total, 246 food items were identified for the 24-h food list, reflecting >75% variation in intake of 27 nutrients and four major food groups. Among the individuals invited, 64% participated in the feasibility study. Of these, 100%, 85% and 68% of participants completed the 24-h food list one, two or three times, respectively. The average time needed to complete the questionnaire was 9 min, and its acceptability by participants was rated as high. The 24-h food list represents a promising new dietary assessment tool that can be used as part of a blended approach combining multiple data sources for valid estimation of usual dietary intake in large-scale cohort studies.


[Kawasaki syndrome].
Kawasaki syndrome was first described in 1967 in Japan. It is due to a generalized vasculitis of probably infectious etiology. Diagnosis is based exclusively on clinical criteria. Both morbidity and mortality are mainly determined by coronary artery involvement. The principal purpose of the present analysis of the 32 patients treated for Kawasaki syndrome at the University Children's Hospital in Berne (22 males = 69%, 11 females = 31%; mean age +/- SD = 2.7 +/- 2 years) was to describe the clinical and laboratory presentation and to evaluate high-risk factors and therapeutic efficacy with regard to course of the disease and cardiac involvement. Treatment has included aspirin and, since 1986, intravenous immunoglobulins (IVIG) as well. Routine electrocardiographic and echocardiographic checks detected 10 patients (31%) with cardiovascular complications, all of whom remained clinically asymptomatic: 9 with carditis (28%) and 3 with coronary artery aneurysms (CAA) (9%). The 3 patients with CAA were boys aged 18-25 months who presented an extremely long duration of fever (12-30 days) and markedly elevated ESR (100-128 mm/h). Since the therapeutic use of high-dose IVIG (9 patients), no CAA has been observed, and carditis in only 2 patients (22%). All patients are clinically cured. The carditis findings and 2 of the 3 CAA completely resolved; one patient has persistent CAA and myopathic cardiomegaly after more than 3 1/2 years. This study, together with the review of the literature, should enable the physician to diagnose and correctly manage the childhood disease Kawasaki syndrome.


Analysis of ionic ratios in myocardial tissue and their relation to cardiac damage.
The authors evaluated the usefulness of the postmortem biochemical analysis of ionic ratios in different parts of the heart and their relation to cardiac damage caused by chest trauma, as observed by anatomopathologic study. Fifty-nine 59 cases were studied, selected from routine necropsies, and samples were taken from different sites of cardiac tissue. The cause of death was trauma in 40 cases and nontraumatic causes in 19 cases. The object of this study was to analyze the levels of Na+, K+, Ca+2, Mg+2, and Zn+2 in different zones of the heart, and the relationship between intracellular and extracellular ion ratios and the different causes of death and any anatomopathologic alterations observed. The biochemical tests revealed a possible relation between the ionic values and cause of death. Alterations in cell membrane permeability and corresponding modification of the ionic ratios were produced earlier than histologic alterations, which need longer to establish themselves whether or not they follow a traumatic process.


Temperature-driven gene expression evolution in natural and laboratory populations highlights the crucial role of correlated fitness effects for polygenic adaptation.
The influence of pleiotropy on adaptive responses is a highly controversial topic, with limited empirical evidence available. Recognizing the pivotal role of the correlation of fitness effects, we designed an experiment to compare the adaptive gene expression evolution of natural and experimental populations. To test this, we studied the evolution of gene expression in response to temperature in two Drosophila species on a natural temperature cline in North America and replicated populations evolving in hot- and cold-temperature regimes. If fitness effects of affected traits are independent, pleiotropy is expected to constrain the adaptive response in both settings, laboratory and natural populations. However, when fitness effects are more correlated in natural populations, adaptation in the wild will be facilitated by pleiotropy. Remarkably, we find evidence for both predicted effects. In both settings, genes with strong pleiotropic effects contribute less to adaptation, indicating that the majority of fitness effects are not correlated. In addition, we discovered that genes involved in adaptation exhibited more pleiotropic effects in natural populations. We propose that this pattern can be explained by a stronger correlation of fitness effects in nature. More insights into the dual role of pleiotropy will be crucial for the understanding of polygenic adaptation.


Potential core species and satellite species in the bacterial community within the rabbit caecum.
A bacteria library was constructed from the caecum of a rabbit maintained under standard conditions. The complete gene 16S rRNA gene was sequenced. The 228 clones obtained were distributed in 70 operational taxonomic units (OTUs). The large majority of the OTUs were composed of one or two clones and seven OTUs contained half of the sequences. Fourteen sequences had high similarity to the sequence already registered in databases (threshold of 97%). Only one of these sequences has been identified as Variovorax sp. (99% identity). Units were distributed mainly (94%) in the Firmicutes phylum. Three sequences were related to Bacteroidetes. Nine clusters were defined in the phylogenic tree. A great diversity of caecal bacteria of the rabbit was shown. Half of the sequences generated in this library were distributed in the phylogenetic tree near the sequences characterized previously in rabbit caecum (potential core species), and the other half of the sequences were well separated (satellite species).


Progress toward poliomyelitis eradication--Nigeria, January 2013-September 2014.
In 1988, the World Health Assembly resolved to interrupt wild poliovirus (WPV) transmission worldwide. By 2013, only three countries remained that had never interrupted WPV transmission: Afghanistan, Nigeria, and Pakistan. Since 2003, northern Nigeria has been a reservoir for WPV reintroduction into 26 previously polio-free countries. In May 2014, the World Health Organization declared the international spread of polio a Public Health Emergency of International Concern. Nigeria's main strategic goal is to interrupt WPV type 1 (WPV1) transmission by the end of 2014, which is also a main objective of the Global Polio Eradication Initiative's Polio Eradication and Endgame Strategic Plan for 2013-2018. This report updates previous reports (4-6) and describes polio eradication activities and progress in Nigeria during January 2013-September 30, 2014. Only six WPV cases had been reported in 2014 through September 30 compared with 49 reported cases during the same period in 2013. The quality of supplemental immunization activities (SIAs) improved during this period; the proportion of local government areas (LGAs) within 11 high-risk states with estimated oral poliovirus vaccine (OPV) campaign coverage at or above the 90% threshold increased from 36% to 67%. However, the number of reported circulating vaccine-derived poliovirus type 2 (cVDPV2) cases increased from four in 2013 to 21 to date in 2014, and surveillance gaps are suggested by genomic sequence analysis and continued detection of WPV1 by environmental surveillance. Interrupting all poliovirus circulation in Nigeria is achievable with continued attention to stopping cVDPV2 transmission, improving the quality of acute flaccid paralysis (AFP) surveillance, increasing vaccination coverage by strengthened routine immunization services, continuing support from all levels of government, and undertaking special initiatives to provide vaccination to children in conflict-affected areas in northeastern Nigeria.


[Sonography of the pancreas].
Sonography was the first non-invasive method that allowed reproducible demonstration of the pancreas. The organ is located in the anterior pararenal space, it is 12-15 cm long. The pancreatic head is in direct contact with the duodenum, the body is located behind the posterial wall of the stomach and the pancreatic tail has topographic relation to the left kidney and to the hilum of the spleen. The main guiding vessel in the transverse scan is the splenic vein. The main value of sonography in acute pancreatitis is description of the course of the inflammatory process and delineation of a biliary etiology. The sensitivity in the demonstration of pseudocysts larger than 2-3 cm is about 90%. In chronic pancreatitis sonography often demonstrates a normal organ. In advanced cases an irregular echopattern with echogenic zones and irregular outer contours are seen. Endoscopic sonography is particularly valuable in demonstrating abnormalities of the pancreatic duct. Dilatation of its tributaries and irregularities of its wall are sharply depicted. 80% of pancreatic carcinomas are echopoor and carcinomas between 2-3 cm in size can be diagnosed by sonography in a few patients. However, the overall prognosis of pancreatic carcinoma has remained unchanged in the last years.


Pregnancy outcomes after treatment for cervical intraepithelial neoplasia in a single NHS hospital.
The objective of this study was to assess the adverse pregnancy outcomes in women who had treatment for cervical intraepithelial neoplasia. This was a retrospective cohort using data linkage. Pathology databases from Whipps Cross University Hospital were used to identify women with a histological sample taken at colposcopy between 1995 and 2009. Births for these women were identified through the hospitals' obstetric database. A total of 876 births (from 721 women) were identified. Logistic regression was used to assess the relationship between adverse pregnancy outcomes and treatment for cervical intraepithelial neoplasia before delivery. Results were adjusted by ethnicity, deprivation, and parity. After taking into account parity, socioeconomic status, and ethnicity, receiving any type of excisional treatment (single or multiple) before birth increased the risk of preterm labor compared with having a punch biopsy only (adjusted relative risk, 1.61; 95% confidence interval, 1.11-2.32). Preterm deliveries that occurred after a spontaneous onset of labor were found to be more likely after treatment for cervical disease (adjusted relative risk, 1.68; 95% confidence interval, 1.11-2.52). Women receiving any type of excisional treatment before delivery are at increased risk of preterm delivery when compared with women attending colposcopy but not treated. Although we took into account the effects of parity, socioeconomic status, and ethnicity, residual confounding factors may be unidentified.


Nonylphenol stimulates fecundity but not population growth rate (lambda) of Folsomia candida.
The toxicity of nonylphenol (NP) to springtails was pronounced at 40 mg/kg dry weight soil, at which no animals survived. Body length and fecundity were the individual life-history traits significantly stimulated by sublethal concentrations of NP during a 64-day experiment. However, the effects of NP on these traits did not result in a statistically significant increase in population growth rate (lambda). Decomposition analysis indicated that fecundity was the main contributor to the (non-significant) changes observed in lambda. However, since the elasticity of fecundity was very low, large changes in fecundity resulted in a minimal effect on lambda. Juvenile survival had the highest elasticity of all traits, but was not affected by NP, and therefore did not contribute to effects on lambda. This study confirms previous studies showing that effects of chemicals on individual life-history traits are attenuated at the population level and that lambda is an appropriate endpoint for ecotoxicological studies.


Vaginal parasitosis.
In two cases the ova of parasitic worms, Ascaris lumbricoides and Enterobius vermicularis, were observed in Papanicolaou-stained vaginal smears. The characteristics of each type of ovum are described.


Ex-Press Mini-Implant in the Management of Ocular Hypertension Secondary to Silicone Oil Tamponed.
This study was designed to compare the success of patients with ocular hypertension, secondary to pars plana vitrectomy and silicone oil tamponade, who received an Ex-PRESS Glaucoma Filtration Device P50 (Alcon Laboratories, Inc. Fort Worth, Texas, USA) to those who had conventional trabeculectomy. The records of 10 eyes of 10 consecutive subjects who had Ex-press implants and 9 eyes of 9 consecutive controls who had trabeculectomy procedures were reviewed. Success was defined as the reduction of intraocular pressure (IOP) in patients who did not require further glaucoma surgery in the eye of note during the entire follow-up. IOP was reduced by 10.3 ± 9.7 mmHg (range -31 to 3) in the Ex-PRESS group and by 13.9 ± 11.4 mmHg (range -35 to -4) in the trabeculectomy group. The difference in the percentage of IOP reduction between the standard trabeculectomy group (42.7%) and the Ex-PRESS group (35.9%) was not statistically significant (P = 0.72). The Ex-PRESS device seems to be at least as effective as the standard trabeculectomy in lowering the IOP of patients with hypertension secondary to pars plana vitrectomy and silicone oil tamponade. Even though the data suggested that the Ex-PRESS device did not result in an overall greater reduction in IOP than trabeculectomy, this does not reach statistical significance.


Molecular cloning of human immune interferon cDNA and its expression in eukaryotic cells.
Starting with mRNA derived from Staphylococcal enterotoxin A induced human splenocytes, dsDNA was synthesized and inserted into unique BamHI site of the eukaryotic expression vector pSV529 (1). A recombinant plasmid containing human immune interferon (IFN-gamma) cDNA was identified by hybridization of plasmid inserted DNA bound onto nitrocellulose filters with mRNA derived from SEA-induced splenocytes, translation of the eluted RNA in Xenopus laevis oocytes and assaying for IFN activity. Plasmids containing the entire human IFN-gamma cDNA sequence were identified by colony hybridization and were sequenced. A unique coding region was identified which predicted a protein of 166 amino acids, the 20 N-terminal amino acids of which presumably represent a signal peptide. After transfection of monkey cells with plasmid DNA isolated from one of the recombinant clones (pHIIF-SV-gamma 1), IFN was excreted into the culture medium. This IFN was not distinguishable from human IFN-gamma by serological criteria or by cell target species specificity.


Neuromuscular trunk activation patterns in back pain patients during one-handed lifting.
To analyze neuromuscular activity patterns of the trunk in healthy controls (H) and back pain patients (BPP) during one-handed lifting of light to heavy loads. After assessment of back pain (graded chronic pain scale according to von Korff) all subjects (n = 43) performed a warm-up (treadmill walking). Next, subjects were instructed to lift 3 × a 20 kg weight placed in front of them (with both hand) onto a table (height: 0.75 m). Subsequently, all subjects lifted with one hand (left-side, 3 repetitions) a weight of 1 kg (light), 10 kg (middle) and 20 kg (heavy) in random order from the ground up onto the table left of them. Trunk muscle activity was assessed with a 12-lead EMG (6 ventral/6 dorsal muscles; 4000 Hz). EMG-RMS (%) was averaged over the 3 repetitions and analyzed for the whole one-handed lifting cycle, then normalized to RMS of the two-handed lifting. Additionally, the mean (normalized) EMG-RMS of four trunk areas [right/left ventral area (VR/VL); right/left dorsal area (DR/DL)] was calculated. Data were analyzed descriptively (mean ± SD) followed by student's t-test comparing H and BPP (α = 0.05). With respect to the unequal distribution of subjects in H and BPP, a matched-group analysis was conducted. Seven healthy controls were gender- and age-matched (group Hmatched) to the 7 BPP. In addition, task failure was calculated and compared between H/Hmatchedvs BPP using χ2. Seven subjects (3m/4f; 32 ± 7 years; 171 ± 7 cm; 65 ± 11 kg) were assigned to BPP (pain grade ≥ 2) and 36 (13m/23f; 28 ± 8 years; 174 ± 10 cm; 71 ± 12 kg) to H (pain grade ≤ 1). H and BPP did not differ significantly in anthropometrics (P > 0.05). All subjects were able to lift the light and middle loads, but 57% of BPP and 22% of H were not able to lift the heavy load (all women). χ2 analysis revealed statistically significant differences in task failure between H vs BPP (P = 0.03). EMG-RMS ranged from 33% ± 10%/30% ± 9% (DL, 1 kg) to 356% ± 148%/283% ± 80% (VR, 20 kg) in H/BPP with no statistical difference between groups regardless of load (P > 0.05). However, the EMG-RMS of the VR was greatest in all lifting tasks for both groups and increased with heavier loads. Heavier loading leads to an increase (2- to 3-fold) in trunk muscle activity with comparable patterns. Heavy loading (20 kg) leads to task failure, especially in women with back pain.


Coarse grained open system quantum dynamics.
We show that the quantum dynamics of a system comprised of a subspace Q coupled to a larger subspace P can be recast as a reduced set of "coarse grained" ordinary differential equations with constant coefficients. These equations can be solved by a single diagonalization of a general complex matrix. The method makes no assumptions about the strength of the couplings between the Q and the P subspaces, nor is there any limitation on the initial population in P. The utility of the method is demonstrated via computations in three following areas: molecular compounds, photonic materials, and condensed phases.


[IMPACT OF PREOPERATIVE BOWEL PREPARATION ON PREVENTION OF SURGICAL SITE INFECTION].
Preoperative preparation of the bowel includes two methods, mechanical bowel preparation (MBP) to remove gross feces and oral antibiotic bowel preparation (OABP) to reduce the colonic bacterial load. MBP and OABP have been performed since the 1940s to 1950s. MBP is routinely performed to reduce the morbidity and mortality of elective colorectal surgery and has been a surgical dogma since the early 1970s. However, numerous prospective, randomized, controlled trials and meta-analyses have questioned the need for MBP in elective colorectal surgery, and a meta-analysis showed that significantly more anastomotic leaks were found after MBP. OABP decreases postoperative infectious complications considerably, although the results differ with the type of antibiotic used. Recently, several large retrospective studies have demonstrated that MBP plus OABP is associated with reduced postoperative infectious complications including surgical site infection rates after elective colorectal surgery. Further prospective, randomized trials of MBP and OABP alone and in combination should be conducted.


Succession of functional bacteria in a denitrification desulphurisation system under mixotrophic conditions.
Large-scale use of ammonia, sulphate, and nitrate in industrial manufacturing has resulted in the generation of industrial wastewater pollutants. However, approaches to eliminate such contamination have not been extensively studied. Accordingly, in this study, we investigated the succession of bacteria under different influent loadings in a mixotrophic denitrification desulphurisation system. Four expanded granular sludge bed reactors were operated simultaneously. The sulphide loading of reactor I was 1.2 kg/m3‧day, the sulphide load of reactor II was 2.4 kg/m3‧day, and the sulphide load of reactor III was 3.6 kg/m3‧day. The molar ratio of carbon versus nitrogen in the influent under each condition was fixed at 1.26:1, and the molar ratio of sulphur versus nitrogen was fixed at 5:6; each reactor was operated for 90 days. Reactor IV was a verification reactor. The three conditions were repeated, and each condition was operated for 90 days. Middle- and late-stage samples under each condition were sequenced using a high-throughput sequencer. Azoarcus, Thauera, Arcobacter, and Pseudomonas were the core genera of the denitrification desulphurisation system under mixotrophic conditions. The genus Azoarcus was a cornerstone genus of mixotrophic conditions, as demonstrated using the random forest model and correlation network analysis.


First report of chronic hepatitis E in renal transplant recipients in Portugal.
Hepatitis E virus (HEV) infection can be responsible for chronic hepatitis in immunocompromised patients, and can rapidly evolve into fibrosis and/or hepatic cirrhosis. We present two cases of chronic hepatitis E, emphasizing the need to be aware of this entity as a growing etiology of hepatitis in transplant and immunocompromised patients.


Activity coefficients in the surface phase of liquid mixtures.
A novel equation for evaluating surface activity coefficients is obtained from a recent thermodynamic formalism describing the surface phase of liquid mixtures. The input quantities are the surface tension, bulk activity coefficients and pure constituent thermophysical properties. It is demonstrated thermodynamically that the order of magnitude of each component surface and bulk activity coefficients must be the same. This order is intrinsically associated with the sign of excess surface tension. Reliable activity coefficients of ethanol and water in the surface phase of their mixtures are computed and reported for the first time, by using literature data for the required input quantities. It is shown that the so-called transferring method for estimating surface activity coefficients is severely flawed, because it leads to contradictory values of predicted excess surface tensions depending on which component this prediction is based.


Changes in the scar tissue structure after cesarean section as a result of manual therapy.
Available statistical data from 2015 show that 28% of pregnancies in developed countries end in cesarean section (CC). Discomfort associated with the scar after surgery is a common complication. This study aimed to evaluate the changes in the structure of the cesarean scar after the application of a scheme of manual therapy. The study included 15 women in the treatment group (TG) and 15 in the control group (CG). The scars were evaluated twice at 5-week intervals with the use of quantitative scales: the Vancouver Scar Scale (VSS), the Manchester Scar Scale (MSS) and the Patient and Observer Scar Assessment Scale (POSAS). During each examination, the scar was compared, using the specified criteria, to the physiological skin, i.e., the tissues directly bordering the incision. During therapy, 8 manual techniques were used during a 4-week program consisting of 30-minute sessions 3 times per week. Patients in the TG showed a statistically significant improvement in all of the analyzed characteristics of the scar. A statistically significant difference was also observed between the results obtained during the 2nd examination (after the therapy) in the TG and the CG. As a result of the therapy, the condition of the scar in the TG significantly improved. Onerous scar-related symptoms were alleviated. The vascularity, hyperpigmentation and distortion of the scar were reduced. The elasticity and pliability of the scar increased, and the height of the scar decreased. The texture, finish and contour of the scar improved. Obtained results suggest that manual therapy of the scar after CC should be a part of the treatment in women during the postpartum period.


Old World fruitbat phylogeny: evidence for convergent evolution and an endemic African clade.
Knud Andersen (1912, Catalogue of the Chiroptera in the Collections of the British Museum: I. Megachiroptera, British Museum of Natural History, London) divided Old World fruitbats (family Pteropodidae) into the rousettine, cynopterine, epomophorine, eonycterine, and notopterine sections. The latter two sections comprise the subfamily Macroglossinae; members of this subfamily exhibit specializations for nectarivory (e.g., elongated, protrusible, brushy tongues) and cluster together in cladistic analyses based on anatomical characters. Other evidence, including single-copy DNA hybridization, suggests that macroglossines are either paraphyletic or polyphyletic; this implies that adaptations for pollen and nectar feeding evolved independently in different macroglossine lineages or were lost in nonmacroglossines after evolving in a more basal common ancestor. Hybridization data also contradict Andersen's phylogeny in providing support for an endemic African clade that includes representatives of three of Andersen's sections. Here, we present complete mitochondrial 12S rRNA and valine tRNA gene sequences for 20 pteropodids, including representatives of all of Andersen's sections, and examine the aforementioned controversies. Maximum likelihood, minimum evolution, and maximum parsimony analyses all contradict macroglossine monophyly and provide support for an African clade that associates Megaloglossus and Lissonycteris and those two with Epomophorus. In conjunction with the DNA hybridization results, there are now independent lines of molecular evidence suggesting: (i) convergent evolution of specializations for nectarivory, at least in Megaloglossus versus other macroglossines, and (ii) a previously unrecognized clade of endemic Africa taxa. Estimates of divergence time based on 12S rRNA and DNA hybridization data are also in good agreement and suggest that extant fruitbats trace back to a common ancestor 25 million to 36 million years ago.


Validity and reliability of a pad test model using a simulated urine leak and healthy continent females.
The objective of this study was to determine the validity and reliability of a modified pad test to assess urinary incontinence. Urine leakage was simulated using normal saline that was dosed onto super-absorbent incontinence pads, and worn by healthy continent females over two sequential 12-hour time periods. The results indicate that the two x 12-hour pad test provides a reliable assessment of urine leak in female subjects.


Amiodarone-induced hyperthyroidism and a thyroid nodule.
To report two cases of thyrotoxicosis associated with amiodarone therapy and to discuss how the presence of a thyroid nodule alters management. We describe two patients with amiodarone-induced hyperthyroidism, review the mechanisms of disease, and outline a strategy for decision making relative to treatment in the presence of a thyroid nodule. Amiodarone-induced thyrotoxicosis occurs by two mechanisms: a direct toxic effect and iodine loading. This condition may be treated medically or surgically, but when discontinuation of amiodarone therapy is not possible and medical management is ineffective, surgical therapy is often necessary. The optimal presurgical management in the cases described required the use of thyroid scanning to determine whether the disease process was attributable to a hyperfunctioning nodule or generalized. The findings were helpful in planning the extent of surgical excision. When surgical treatment is planned for patients with a solitary thyroid nodule and amiodarone-induced hyperthyroidism, preoperative thyroid scanning will direct the surgeon to perform either subtotal thyroidectomy for diffuse disease or lobectomy for a hyperfunctioning nodule.


Laparoscopic total pancreatectomy for multiple metastasis of renal cell carcinoma of the pancreas: a case report and literature review.
Advances in surgical techniques and laparoscopic instruments have resulted in the development of laparoscopic pancreatic surgery. Total pancreaticoduodenectomy is performed for treating benign and borderline pancreatic disease involving the whole pancreas. Here, we report a case of metastatic renal cell carcinoma in the pancreas, treated by laparoscopic pylorus-preserving total pancreaticoduodenectomy. A 59-year-old woman was diagnosed with metastatic renal cell carcinoma. Multiple metastatic lesions were found on routine follow-up. She had a history of radical video-assisted right-nephrectomy for renal cell carcinoma (conventional type, pT1) in November 2003, without any recurrence. However, in 2014, a routine health checkup revealed multiple enhancing lesions throughout the pancreas. Positron emission tomography showed a suspicious 4-cm lesion in her left thyroid. Laparoscopic pylorus-preserving total pancreaticoduodenectomy with splenectomy was performed, along with simultaneous left total thyroidectomy with central compartment node dissection for metastatic renal cell carcinomas. The total operation time was 441 min, with an estimated blood loss of 150 ml; no transfusion was administered. Her hospital stay was 12 days. The histopath report confirmed metastatic renal cell carcinoma in the pancreas and left thyroid. Based on literature reviews, we further tried to estimate the oncologic outcome of total pancreatectomy in multiple pancreatic metastasis of renal cell carcinoma. Laparoscopic pylorus-preserving total pancreaticoduodenectomy is feasible and safe, even in cases of metastatic renal cell carcinoma.


Evaluation of the extent of initial Maillard reaction during cooking some vegetables by direct measurement of the Amadori compounds.
During vegetable cooking, one of the most notable and common chemical reactions is the Maillard reaction, which occurs as a result of thermal treatment and dehydration. Amadori compound determination provides a very sensitive indicator for early detection of quality changes caused by the Maillard reaction, as well as to retrospectively assess the heat treatment or storage conditions to which the product has been subjected. In this paper, a hydrophilic interaction liquid chromatographic-electrospray ionization-tandem mass spectrometric method was developed for the analysis of eight Amadori compounds, and the initial steps of the Maillard reaction during cooking (steaming, frying and baking) bell pepper, red pepper, yellow onion, purple onion, tomato and carrot were also assessed by quantitative determination of these Amadori compounds. These culinary treatments reduced moisture and increased the total content of Amadori compounds, which was not dependent on the type of vegetable or cooking method. Moreover, the effect of steaming on Amadori compound content and water loss was less than that by baking and frying vegetables. Further studies showed that the combination of high temperature and short time may lead to lower formation of Amadori compounds when baking vegetables. Culinary methods differently affected the extent of initial Maillard reaction when vegetables were made into home-cooked products. © 2017 Society of Chemical Industry.


The neuropeptide vasoactive intestinal peptide: direct effects on immune cells and involvement in inflammatory and autoimmune diseases.
Neuropeptides represent an important category of endogenous contributors to the establishment and maintenance of immune deviation in the immune-privileged organs such as the CNS and in the control of acute inflammation in the peripheral immune organs. Vasoactive intestinal peptide (VIP) is a major immunoregulatory neuropeptide widely distributed in the central and peripheral nervous system. In addition to neurones, VIP is synthesized by immune cells which also express VIP receptors. Here, we review the current information on VIP production and VIP-receptor-mediated effects in the immune system, the role of endogenous and exogenous VIP in inflammatory and autoimmune disorders and the present and future VIP therapeutic approaches.


Effects of Exogenous Glucoamylase Enzymes Alone or in Combination with a Neutral Protease on Apparent Total Tract Digestibility and Feces D-Lactate in Crossbred Angus Bulls Fed a Ration Rich in Rolled Corn.
The aim of this study was to evaluate the effect of two glucoamylases (GA) and the combination of one GA with a neutral protease on apparent total tract digestibility in beef bulls fed a total mixed ration (TMR) rich in rolled corn. Sixteen Angus beef bulls (266 ± 4.9 kg of initial BW, and 182 ± 1.7 d of age) were distributed in 4 blocks, each block consisted of 4 animals balanced by BW. The experimental design was a 4 × 4 Latin square (4 blocks and 4 periods, 2 w per period). Four treatments were tested; (1) control, (2) GA preparation from Trichoderma reesei (TrGA); (3) GA from Aspergillus fumigatus (AfuGA); (4) AfuGA in combination with a neutral protease from Bacillus amyloliquefaciens (BamPro). Apparent total tract digestibility and fecal D-lactate concentration were analyzed. Enzyme supplementation, regardless of enzyme type, increased apparent total tract digestibility of dry matter (from 66.7% to 73.1% ± 2.01), and starch (from 74.7% to 81.8% ± 2.25), without affecting feces D-lactate concentration. Irrespective of glucoamylase type, glucoamylase supplementation improved apparent digestibility of dry matter and starch, and the addition of a protease did not have additional benefits on nutrient digestibility.


Immunotoxic effects of exposure to the antifouling copper(I) biocide on target and nontarget bivalve species: a comparative in vitro study between Mytilus galloprovincialis and Ruditapes philippinarum.
Edible bivalves constitute an important bioresource from an economic point of view, and studies on their immune responses to environmental pollutants are crucial for both the preservation of biodiversity and economic reasons. The worldwide diffusion of copper(I)-based antifouling paints has increased copper leaching into coastal environments and its potential impact on both target and nontarget organisms. In this study, immunotoxicity assays were carried out with short-term (60 min) cultures of hemocytes from the bivalves Mytilus galloprovincialis-a mussel dominant in the macrofouling community-and Ruditapes philippinarum-a clam dominant in the soft-sediment community-exposed to CuCl to compare the toxic effects on their immune responses. The LC50 values were similar, 40 μM (3.94 mg L-1) for the mussel and 44 μM (4.33 mg L-1) for the clam. In both species, apoptosis occurred after exposure to 1 µM (98.9 μg L-1) CuCl, the concentration able to significantly increase the intracellular Ca2+ content. Biomarkers of cell morphology and motility revealed microfilament disruption, a significant decrease in yeast phagocytosis and lysosome hydrolase (β-glucuronidase) inhibition beginning from 0.5 µM (49.5 μg L-1) CuCl in both the mussel and clam. The same concentration of CuCl affected biomarkers of oxidative stress, as a significant decrease in reduced glutathione content in the cytoplasm and inhibition of mitochondrial cytochrome-c oxidase (COX) were detected in both species. Comparison of the biomarkers showed that clam is more sensitive than the mussel regarding alterations to the lysosomal membrane and reactive oxygen species (ROS) production, which supports the potential harmful effects of antifouling biocides on the survival of nontarget pivotal species in the coastal community.


Pf1 bacteriophage hydration by magic angle spinning solid-state NMR.
High resolution two- and three-dimensional heteronuclear correlation spectroscopy ((1)H-(13)C, (1)H-(15)N, and (1)H-(13)C-(13)C HETCOR) has provided a detailed characterization of the internal and external hydration water of the Pf1 virion. This long and slender virion (2000 nm × 7 nm) contains highly stretched DNA within a capsid of small protein subunits, each only 46 amino acid residues. HETCOR cross-peaks have been unambiguously assigned to 25 amino acids, including most external residues 1-21 as well as residues 39-40 and 43-46 deep inside the virion. In addition, the deoxyribose rings of the DNA near the virion axis are in contact with water. The sets of cross-peaks to the DNA and to all 25 amino acid residues were from the same hydration water (1)H resonance; some of the assigned residues do not have exchangeable side-chain protons. A mapping of the contacts onto structural models indicates the presence of water "tunnels" through a highly hydrophobic region of the capsid. The present results significantly extend and modify results from a lower resolution study, and yield a comprehensive hydration surface map of Pf1. In addition, the internal water could be distinguished from external hydration water by means of paramagnetic relaxation enhancement. The internal water population may serve as a conveniently localized magnetization reservoir for structural studies.


Ethical Decision-Making in the Pharmacists' Patient Care Process.
The intent of the Pharmacists' Patient Care Process (PPCP) is to provide a comprehensive approach to team-based, comprehensive patient-centered care. Consideration of potential ethical issues is a necessary component of comprehensive care provision and is a requirement of accreditation standards, but there is no specific mention of ethics in any of the phases of the PPCP. A more explicit incorporation of ethical decision-making into the PPCP should help faculty involved in teaching ethics and students who need to incorporate ethical considerations into the PPCP to provide optimal patient care. The aims of this commentary are to provide faculty with a foundational introduction to ethics and an explicit approach for incorporating ethical decision-making into the PPCP.


Predicting phonetic transcription agreement: insights from research in infant vocalizations.
The purpose of this study is to provide new perspectives on correlates of phonetic transcription agreement. Our research focuses on phonetic transcription and coding of infant vocalizations. The findings are presumed to be broadly applicable to other difficult cases of transcription, such as found in severe disorders of speech, which similarly result in low reliability for a variety of reasons. We evaluated the predictiveness of two factors not previously documented in the literature as influencing transcription agreement: canonicity and coder confidence. Transcribers coded samples of infant vocalizations, judging both canonicity and confidence. Correlation results showed that canonicity and confidence were strongly related to agreement levels, and regression results showed that canonicity and confidence both contributed significantly to explanation of variance. Specifically, the results suggest that canonicity plays a major role in transcription agreement when utterances involve supraglottal articulation, with coder confidence offering additional power in predicting transcription agreement.


Heavy metal incorporation in foraminiferal calcite under variable environmental and acute level seawater pollution: multi-element culture experiments for Amphisorus hemprichii.
The accelerated release of heavy metals into the coastal environments due to increasing anthropogenic activities poses a severe threat to local marine ecosystems and food chains. Although some heavy metals are essential nutrients for plants and animals, higher concentrations can be toxic and hazardous. To mitigate this threat, developing quantifiable proxies for monitoring heavy metal concentrations in near-shore marine environments is essential. Here, we describe culture experiments to quantify uptake of some heavy metals using live juvenile specimens of the large benthic foraminifera (LBF) Amphisorus hemprichii collected from the subtropical waters of Rottnest Island located ~20 km offshore Perth, South West Australia. The uptake of Mn, Ni, Cd, and Pb in the newly precipitated chambers of Amphisorus hemprichii in the laboratory was characterized using the micro-analytical technique, laser ablation inductively coupled plasma mass spectrometry. We found no significant increase in Mn, Ni, Cd, and Pb incorporation in the tests of Amphisorus hemprichii with increasing temperature and light intensities. Importantly, we found that changes in the concentrations of Mn, Ni, and Cd in the A. hemprichii tests are directly proportional to those in the culture solution over a wide range of concentrations. The calculated partition coefficients for Mn, Ni, and Cd from our culture experiments are 1.3±0.2, 0.3±0.04, 2.6±0.3, respectively. These multi-element calibration studies now enable A. hemprichii to be utilized as a naturally occurring bio-archive to quantitatively monitor the anthropogenic pollution of Mn, Ni, and Cd in coastal waters.


Cell stress promotes the association of phosphorylated HspB1 with F-actin.
Previous studies have suggested that the small heat shock protein, HspB1, has a direct influence on the dynamics of cytoskeletal elements, in particular, filamentous actin (F-actin) polymerization. In this study we have assessed the influence of HspB1 phosphorylation on its interaction(s) with F-actin. We first determined the distribution of endogenous non-phosphorylated HspB1, phosphorylated HspB1 and F-actin in neuroendocrine PC12 cells by immunocytochemistry and confocal microscopy. We then investigated a potential direct interaction between HspB1 with F-actin by precipitating F-actin directly with biotinylated phalloidin followed by Western analyses; the reverse immunoprecipitation of HspB1 was also carried out. The phosphorylation influence of HspB1 in this interaction was investigated by using pharmacologic inhibition of p38 MAPK. In control cells, HspB1 interacts with F-actin as a predominantly non-phosphorylated protein, but subsequent to stress there is a redistribution of HspB1 to the cytoskeletal fraction and a significantly increased association of pHspB1 with F-actin. Our data demonstrate HspB1 is found in a complex with F-actin both in phosphorylated and non-phosphorylated forms, with an increased association of pHspB1 with F-actin after heat stress. Overall, our study combines both cellular and biochemical approaches to show cellular localization and direct demonstration of an interaction between endogenous HspB1 and F-actin using methodolgy that specifically isolates F-actin.


Stimulatory role of substance P on gonadotropin release in ovariectomized rats.
Substance P (SP) has been shown to be present in the hypothalamus and anterior pituitary. To evaluate a possible physiological role of endogenous SP in the control of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release, specific antiserum against SP (anti-SP) was injected intraventricularly (3 microliters into the third ventricle) or intravenously (50 or 200 microliters) into conscious, ovariectomized (OVX) rats. Third ventricular injection of the antiserum induced a significant decrease in both plasma LH and FSH levels when compared to values in control animals injected with normal rabbit serum (p less than 0.01 and p less than 0.025, respectively). The effect was observed within 10 mi and levels remained suppressed for 60 min. In contrast, intravenous injection of large doses of anti-SP had no effect on the release of both hormones. In order to confirm the stimulatory effect of SP itself, synthetic SP was injected intravenously and intraventricularly into estrogen-primed (E-primed), OVX rats. Synthetic SP dramatically stimulated LH release, but not FSH release when injected either intravenously or intraventricularly at doses of 10 and 50 micrograms (p less than 0.001, p less than 0.005 vs. control, respectively). To investigate any direct action of SP on gonadotropin release from the anterior pituitary gland, synthetic SP was incubated with dispersed anterior pituitary cells harvested from E-primed OVX rats. SP did not affect the release of gonadotropins in vitro. These results indicate that endogenous hypothalamic SP exerts a tonic stimulatory hypothalamic control of basal gonadotropin release in OVX rats.


Clinical characterization of neck pain in migraine.
Several extracranial symptoms, including somatic pain syndormes, are known to occur in migraine. Though neck pain has been occasionally described with migraine, its precise association and nature is not yet clear. To study the incidence and characteristics of neck pain in migraine with particular emphasis on its occurrence as a trigger or a part of the symptom complex of migraine, as well as its association with different phases of the migraine attack. We interviewed 391 migraine patients for 18 months. All patients who reported neck pain anytime during the migraine phase were analyzed for their demographic profile, headache and neck pain characteristics, the associated conditions, and other clinical features. One hundred and sixty-six (42.5%) patients reported neck pain anytime during the attack (61.5% were female patients and the mean age was 35.8 years). A total of 82.7% patients had migraine without aura and 75.3% had episodic migraine at the onset. In 53 patients (32%), neck pain was a trigger, and in the rest (n = 113, 68%), neck pain was a part of migraine symtomatology. Fifty-seven patients (34.3%) noticed neck pain before the onset of headache; 148 patients (89.2%) reported neck pain at the onset of headache, and 46 patients (27.7%) experienced neck pain after the resolution of headache. The characteristic feature of migraine, such as the unilateral side shifting type of headache, was seen in only 54.2% of the patients, and the throbbing pain quality was seen in 75.2% of the patients. There was no significant difference in the nonheadache symptoms (P = 0.587) and cranial autonomic symptoms (P = 0.596) between the neck pain triggered migraine patients and those having neck pain as a part of the attack. These data indicate that neck pain is a very common feature of migraine attacks and is likely to be either a trigger or a part of the migraine attack. Contrary to the established concept, however, neck pain as a prodromal or postdromal migraine symptom was less common. Careful history taking is required to diagnose neck pain as a feature of migraine and to differentiate it from secondary headache due to a cervical pathology for avoiding unnecessary imaging or other investigations.


Silencing of FANCI Promotes DNA Damage and Sensitizes Ovarian Cancer Cells to Carboplatin.
Ovarian cancer (OVCA) has unique epigenetic alterations and defects in homologous recombination (HR). Despite initial sensitivity to platinum-based chemotherapy, HR dysfunctional tumors eventually acquire drug resistance. Fanconi anemia (FA) is characterized by bone marrow failure (BMF) and a reduced ability to eradicate DNA interstrand cross-links (ICL). However, the mechanism of chemoresistance mediated by FANCI was unclear in OVCA. We explore to identify whether FANCI was involved in chemoresistance in OVCA. FANCI expression and epigenetic alterations were analyzed, respectively, using TIMER and cBioPortal. The correlation between FANCI expression and the survival of OVCA patients was analyzed using Kaplan-Meier Plotter, GSE63885, and TCGA-OVCA dataset. FANCI expression in OVCA was detected by immunohistochemistry. Cell proliferation, migration, and invasion in FANCI inhibiting cells were assessed by CCK-8 and Transwell. Apoptosis and DNA damage were examined by flow cytometry and immunofluorescence. Meanwhile, the activity of caspase 3/7 was detected by Caspase-Glo® 3/7 kit. In addition, the expression of FANCI, γH2AX, and apoptosis effectors was examined by Western blot. FANCI has copy number variations (CNVs) in OVCA. The high expression of FANCI in OVCA patients was associated with poor survival. Moreover, FANCI expression was correlated with the response to chemotherapy in OVCA. FANCI expression in OVCA cells was induced by carboplatin in a time-dependent manner. Silencing of FANCI had no effect on cell proliferation, but hindered OVCA cell migration and invasion. Mechanically, knockdown of FANCI enhanced DNA damage-induced apoptosis through the CHK1/2-P53-P21 pathway. FANCI may be a potential therapeutic target for OVCA patients.


Efficient and Stable Ternary Organic Solar Cells Based on Two Planar Nonfullerene Acceptors with Tunable Crystallinity and Phase Miscibility.
Planar perylene diimides (PDIs), when used as nonfullerene acceptors for organic photovoltaics, are constrained by their large π-aggregation in solid state. To tackle this issue, another planar nonfullerene acceptor 3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone)-5,5,11,11-tetrakis(4-hexylphenyl)-dithieno[2,3-d:2',3'-d']-s-indaceno[1,2-b:5,6-b']dithiophene (ITIC) with weak crystallinity and near-infrared light absorption is introduced into the PTB7-Th:PDI binary blend to fabricate efficient and stable ternary solar cells. We have finely tuned the PDI/ITIC weight ratio to investigate the influences of individual ITIC and PDI on the optical, electronic, and morphological properties of the PTB7-Th:ITIC:PDI ternary blend. Compared to the binary blend, complementary optical absorption is achieved in all ternary blends. More importantly, it is found that ITIC plays a critical role on largely suppressing the PDI aggregates in the PTB7-Th:PDI blend, while PDI aids to form an interpenetrating network morphology to facilitate charge transport in the PTB7-Th:ITIC blend. Consequently, when the PDI/ITIC ratio is 3:7 (w/w), the PTB7-Th:ITIC:PDI based inverted solar cells exhibit the highest power conversion efficiency of 8.64% due to their favorable out-of-plane π-π stacking, finest phase-separation morphology, and highest charge mobility. Remarkably, the optimal cells that are solution-processed in air show the promising efficiency of 7.09%, suggesting good ambient stability of such ternary solar cells.


Application of paramagnetic beads for purifying Bacillus anthracis protective antigen.
Paramagnetic beads coated with Protein G and Tosylactivated-280 dynabeads have been used to purify Bacillus anthracis protective antigen from a liquid culture. The obtained protein was used in the enzyme-linked immunosorbent assay test to detect B. anthracis protective antigen antibodies in human sera collected from immunized individuals. The purification method using paramagnetic beads is very effective. It is fast, easy and may be carried out practically in any laboratory.


[Preoperative overnight airway pressure measurement for predicting the outcome of revised uvulopalatopharyngoplasty].
The distribution of upper airway obstruction sites can be identified quantitatively and dynamically with continuous airway pressure measurements in obstructive sleep apnea hypopnea syndrome ( OSAHS) patients. Its value as a clinical predictor for the outcome of revised uvulopalatopharyngoplasty was evaluated. The upper airway obstruction sites (transpalatal level, tongue base or hypolarynx level) were determined preoperatively with overnight upper airway pressure monitoring and concurrent polysomnography (PSG). Of one's total amount of obstructive events, the proportion of apnea/hypopnea events located at Transpalatal level was quantified as contribution of transpalatal obstruction. Of all OSAHS patients, 26 males and 1 female underwent revised uvulopalatopharyngoplasty (2 had same stage transpalatal advancement pharyngoplasty) and had follow-up PSG 6. 33 +/- 0.84 months after surgery. The relationship of transpalatal obstruction proportion, age, tonsil size and body mass index (BMI) and the reduction in apnoea hypopnea index (AHI) was analyzed. The AHI (times/hr) of 27 subjects decreased from 63.9 +/- 20.7 to 28.4 +/- 25.4. The response rate was 51.9% (defined as AHI reduction over 50%). Correlation between the transpalatal obstruction proportion and the AHI reduction percentage was significant (r = 0.609), so was the degree of the tonsil size (r = 0.511). The proportion of tongue base level obstruction showed a negative correlation for the AHI reduction. Patients with oropharynx obstruction percentage > or = 70% had a success rate of 90% and all patients with oropharynx obstruction percentage <60% responded poorly to the operation. The regression model showed distribution of obstructive sites, along with tonsil size and other PSG parameters could predict 66.7% of the postoperative AHI of transpalatal level surgery (F = 6.701, P = 0.001) . Contribution of transpalatal level obstruction has significant predictive value to the outcome of transpalatal level surgery in OSAHS patients.


Discovering determinants influencing faith community nursing practice.
Faith community nursing (FCN) is an important healthcare delivery system for individuals, families, and communities. Determinants are factors that might influence FCN care. A literature review isolated eight determinants that influence practice; however, there are no clear causal relationships linking specific determinants to specific practice changes. Research is needed to assess how determinants influence practice and outcomes, and provide evidence-based solutions to isolate and manage determinants. A Conceptual Model of FCN, Theoretical Definitions and a Diagram of Determinants of FCN Practice are provided.


Influencing policymaking for maltreated children and their families.
Public policy can be a powerful tool for children and their families. Accordingly, this article addresses how psychologists and other child-oriented researchers can leverage this tool to ensure that child and family issues, specifically issues related to child abuse and neglect, receive adequate attention. We encourage a bidirectional relationship between policymakers and experts in child maltreatment through which policymakers solicit and employ relevant expertise, and psychologists, in turn, provide useful information to policymakers. To facilitate such relationships, this article offers practical guidance to psychologists on understanding the policymaking process, gaining familiarity with relevant policy, communicating effectively with policymakers, and understanding the unique contributions that psychologists can make to the policy process.


Estimated equivalency of vitamin D production from natural sun exposure versus oral vitamin D supplementation across seasons at two US latitudes.
The relationship between oral vitamin D supplementation and cutaneous photosynthesis is not well understood. We sought to provide estimates of the equivalency of vitamin D production from natural sun exposure versus oral supplementation. Using the FastRT simulation tool, we determined sun exposure times needed to achieve serum vitamin D(3) concentrations equivalent to 400 or 1000 IU vitamin D for individuals of various Fitzpatrick skin types living in Miami, FL, and Boston, MA, during the months of January, April, July, and October. Peak ultraviolet B irradiation for vitamin D synthesis occurs around 12 pm Eastern Standard Time (EST). In Boston, MA, from April to October at 12 pm EST an individual with type III skin, with 25.5% of the body surface area exposed, would need to spend 3 to 8 minutes in the sun to synthesize 400 IU of vitamin D. It is difficult to synthesize vitamin D during the winter in Boston, MA. For all study months in Miami, FL, an individual with type III skin would need to spend 3 to 6 minutes at 12 pm EST to synthesize 400 IU. Vitamin D synthesis occurs faster in individuals with lighter Fitzpatrick skin types. The duration to attain 1000 IU of vitamin D is longer in all scenarios. Results of the computer model are only approximations. In addition, calculations were made based on the assumption that (1/4) of 1 minimal erythema dose directed at (1/4) body surface area is equal to 1000 IU of oral vitamin D. Although it may be tempting to recommend intentional sun exposure based on our findings, it is difficult, if not impossible to titrate one's exposure. There are well-known detrimental side effects of ultraviolet irradiation. Therefore, oral supplementation remains the safest way for increasing vitamin D status.


Pharmacology of benzamidine-type thrombin inhibitors.
Findings on the pharmacology of derivatives of benzamidine characterized as potent competitive inhibitors of the clotting enzyme thrombin were presented including data on their toxicity. Bis-benzamidines and amidinophenylalanine amides were shown to exert pharmacodynamic effects in intact animals and isolated preparations (hypotension; influence on smooth muscle reactions to serotonin and histamine). Studies with 14C-4-amidinophenylpyruvic acid and 3H-N alpha-tosyl-(3-amidino)-phenylalanine piperidide on the pharmacokinetics in rabbits showed that benzamidine derivatives are suited, in principle, for use as anticoagulants in vivo. Pharmacokinetic properties of individual thrombin inhibitors have to be taken into account in order to reach and maintain adequate plasma levels. The antithrombotic effect of benzamidine-type thrombin inhibitors in animals experiments is directly related to their antithrombin activity.


Film processing and the environment. Reducing pollution, water consumption, and costs.
X-ray film processing is associated with pollution from photo chemicals and from the water used to rinse the film. We tested a new processing system that was aimed at reducing both environmental pollution and costs through the use of solid photo chemicals and recirculation of the rinsing water. Before and after the installation of new mixers for the solid chemicals and a system for recirculating the rinsing water, we measured: water consumption, processor function quality, image quality, archivability, and the waste-silver content in the rinsing water. After the installation of a simple system for recirculating the rinsing water, there was an 88% reduction in water and film consumption as shown in the amount of water/m2 film that was used. At the same time, the release of silver-contaminated rinsing water directly into the sewers was stopped. Image quality remained unchanged. Archivability was assessed at more than 100 years. The solid photo chemicals and specially designed mixers proved efficient and provided a stable image quality of high standard. It was thus possible to reduce the risk of pollution from the transportation, storage and handling of liquid chemicals. A simple recirculation system for the rinsing water would significantly reduce water consumption and eliminate contamination of the environment by silver. The on-site preparation of photo chemicals proved viable and reduced the costs of film processing.


Human immunodeficiency virus DNA is present in a high percentage of CD4+ lymphocytes of seropositive individuals.
Human immunodeficiency virus type 1 (HIV-1) infects predominantly CD4+ cells in human peripheral blood and infection is associated with CD4+ lymphocyte dysfunction in patients with AIDS. To determine the frequency of HIV-1 infection in CD4+ lymphocytes in vivo, peripheral blood CD4+ lymphocytes were isolated by fluorescence-activated cell sorting from HIV-1-infected persons with clinical disease ranging from asymptomatic to AIDS. Using standard and booster polymerase chain reaction analyses, study patients with AIDS and AIDS-related complex (ARC) were found to harbor the HIV-1 genome in at least 10% of CD4+ lymphocytes, and approximately 10-fold less infected cells were found in those with asymptomatic infection. In addition, the peripheral blood mononuclear cells from patients with ARC frequently contained a higher absolute number of HIV-1-infected CD4+ lymphocytes than those with AIDS or asymptomatic infection. It is likely that this high level of infection of CD4+ lymphocytes is the primary cause for the progressive immunologic deficiency observed in patients infected with HIV-1.


Effect of caffeine on alcohol consumption and alcohol-induced conditioned place preference in rodents.
Background The aim of the study was to determine the effect of caffeine on alcohol consumption with or without deprivation and alcohol-induced conditioned place preference. Methods In the present study, we examined the effects of caffeine (2.5, 5 and 10 mg/kg) on alcohol consumption in Wistar rats with or without periods of deprivation in an unlimited-access, two-bottle, free choice drinking procedure after a stable baseline alcohol consumption was established. Conditioned place preference (CPP) was established by intraperitoneal injections of alcohol (2 g/kg) in a 12-day conditioning schedule in mice. The effect of caffeine (3 mg/kg) on CPP expression was determined by a final post-conditioning test following 12 conditioning sessions with alcohol. The effect of caffeine (3 mg/kg) on the reinstatement of alcohol-induced CPP was determined in a final post-conditioning test following 12 conditioning sessions with alcohol and the extinction of alcohol-induced CPP. Results Alcohol deprivation for 3 days did not result in alcohol deprivation effect (ADE). While caffeine (10 mg/kg) caused a significant (p<0.05) reduction in alcohol consumption compared with the baseline following a period of alcohol deprivation, it did not cause a change in alcohol consumption compared with the baseline in the study without alcohol deprivation phase. Caffeine significantly (p<0.05) reduced the expression of alcohol-induced CPP compared to saline and blocked the reinstatement of alcohol-induced CPP following the injection of a priming dose (0.4 g/kg) of alcohol. Conclusions Given that caffeine is an adenosine receptor antagonist, our findings suggest a role for adenosine receptors in the alcohol reward and alcohol-seeking behaviour.


Real-world experience of calcipotriene and betamethasone dipropionate foam 0.005%/0.064% in the treatment of adults with psoriasis in the United States.
Background: Clinical trials have established calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) foam as a well-tolerated and efficacious topical therapy for psoriasis. Methods: A chart review of 24 US healthcare providers gathered real-world information (clinical characteristics and outcomes, safety, and resource utilization) for patients (≥18 years old) prescribed Cal/BD foam between January 1 and October 31, 2016, along with healthcare provider characteristics and perceptions of Cal/BD foam. Results: Data were reported from 105 patients and 177 active psoriatic lesions. Cal/BD foam was applied once-daily; the prescription was 4 weeks for 69/177 (39%) lesions (median 4, range 1-26 weeks). Knees (n = 41; 23%) and elbows (n = 37; 20%) were the most frequently treated areas. Among 114 lesions, severity improved from "mild"/"moderate"/"severe" to "clear"/"almost clear" in 71%, and 54% had a clinically significant improvement (two-step/greater improvement) in lesion severity from baseline. Of 128 lesions with baseline itch, 90% were not itchy at the best treatment response. Most healthcare providers reported prescribing Cal/BD foam because of its overall efficacy (n = 20/23; 87%). Adverse events were reported in 1/105 patients (1%). Conclusion: Data from real clinical practice demonstrate that Cal/BD foam improves psoriasis disease severity and associated itch in patients and further extend results of clinical trials.


Periodontitis and glycemic control in diabetes: NHANES 2009 to 2012.
This study examines the association between periodontitis, diabetes (DM), and glycemic control. National Health and Nutrition Examination Survey data for 2009 to 2012 were analyzed. Periodontitis status of each participant was assessed using the full-mouth periodontal examination protocol, classified using the Centers for Disease Control and Prevention and the American Academy of Periodontology surveillance case definition for total periodontitis. Self-reported DM status was defined as yes or no. Glycemic control was assessed using glycohemoglobin data at cutoff points of 7.0%, 7.5%, 8.0%, 8.5%, and 9.0%. Descriptive statistics and logistic regression analyses were performed, and all analyses were adjusted for the survey design. Overall, 7,042 adults ≥30 years old with complete data were included in the study. The mean glycohemoglobin levels for individuals with and without periodontitis were 5.9% and 5.6%, respectively, and increased to 7.4% and 7.0% for participants with DM. The majority of participants with and without periodontitis were aged 50 to 64 and 35 to 49 years (37.4% versus 44.5%), respectively. In the bivariate analysis, several demographic factors were significantly associated with having periodontitis, including self-reported DM status and glycemic control. In the multivariate analysis, demographic factors, glycohemoglobin cutoff values of 8.0%, 8.5%, and 9.0%, and mean glycohemoglobin level remained significant, but self-reported DM status was not. This study demonstrates that glycohemoglobin and demographic factors are significantly associated with periodontitis, but not self-reported status.


The Efficacy of Platinum Chemotherapy in a Japanese Malignant Melanoma Patient With a BRCA2 Mutation Identified by Gene Panel Testing.
A BRCA2 mutation increases the chance of developing cancer and has been linked to several diseases, including hereditary breast, ovarian, pancreatic, and prostate cancers. We present a case of advanced malignant melanoma treated with platinum-containing chemotherapy and demonstrate a momentarily favorable clinical outcome as determined by a Next Generation Sequencer (NGS) gene panel testing. A 54-year-old female with BRAF wild-type of anal primary melanoma received adjuvant immunotherapy with nivolumab following surgical resection. Novel distant lung metastasis was identified four months after the adjuvant therapy. Multi-gene panel testing figured out another potential treatment strategy using a sample from a distant metastatic tumor and identified a BRCA2 mutation in the tumor. Based on the sensitivity to platinum agents in BRCA2 mutation-positive tumors, DAC-Tam therapy (Dacarbazine, Nimustine, Cisplatin, and Tamoxifen) was administrated and showed tumor size reduction. After five rounds of DAC-Tam treatment, the metastatic lesion decreased from 17 mm to 5 mm. The parent was treated with platinum and Dacarbazine alone because of deteriorated renal function and grade 3 myelosuppression. In addition, the tumor showed resistance to the platinum plus Dacarbazine chemotherapy. Her chemotherapy-induced renal failure and bone marrow suppression did not improve well. Additionally, she felt significant weakness due to poor dietary intake and did not want to receive additional chemotherapy. To relieve her symptoms, she and her family desired the best supporting care and moved her to another hospital. The patient died 12 months after submitting the gene panel.


Nano-hydroxyapatite alleviates the detrimental effects of heavy metals on plant growth and soil microbes in e-waste-contaminated soil.
The crude recycling activities of e-waste have led to the severe and complex contamination of e-waste workshop topsoil (0-10 cm) by heavy metals. After nano-hydroxyapatite (NHAp) application in June 2013, plant and soil samples were obtained in November 2013, December 2013, March 2014 and June 2014. The results showed that NHAp effectively reduced the concentration of CaCl2-extractable Pb, Cu, Cd, and Zn in the topsoil and significantly reduced the metal content in ryegrass and also increased the plant biomass compared with that of the control. Moreover, the concentrations of CaCl2-extractable metals in the soil decreased with increasing NHAp. NHAp application also increased the activities of soil urease, phosphatase and dehydrogenase. Moreover, the soil bacterial diversity and community structure were also altered after NHAp application. Particularly, Stenotrophomonas sp. and Bacteroides percentages were increased. Our work proves that NHAp application can alleviate the detrimental effects of heavy metals on plants grown in e-waste-contaminated soil and soil enzyme activities, as well as soil microbial diversity.


Indomethacin as a diagnostic and therapeutic tool in the management of progressive cervical shortening diagnosed by trans-vaginal sonography.
To evaluate the role of indomethacin in discriminating between preterm labour and cervical insufficiency-related cervical shortening. Retrospective analysis of all cases of cervical shortening on singleton gestations. All patients were treated according to our protocol with one or more of the following three modalities: (1) bed rest only, (2) bed rest and indomethacin and (3) cervical cerclage, bed rest, and indomethacin. foetal loss <24 weeks, birth weight, delivery <34 weeks, and delivery <37 weeks. We treated 342 patients: 167 (48.8%) with bed rest only, 21 (6.1%) with cerclage, and 154 (45.1%) with indomethacin. By 28 weeks 56 (16.3%) remained stable or improved with bed rest only, 91 (26.6%) failed indomethacin and required cerclage, and the remaining 173 (50.6%) responded well to indomethacin and nifedipine. Birth weight was 3119 g ± 651 (SD) and GA at delivery 37.4 weeks ± 2.5 (SD). Of the 342 patients, 4 (1.2%) aborted <24 weeks, 1 was terminated (achondroplasia), 320 (93.6%) patients delivered >34 weeks and 301 (88.1%) >37 weeks. Use of indomethacin in patients with cervical shortening discriminates patients with cervical insufficiency from those in premature labour and improves outcomes in comparison to existing published reports.


Why Ligand Doping Increases the Fluorescence of an Anthracene-Based Metal-Organic Framework.
Metal-organic frameworks (MOFs) built from fluorescent ligands frequently exhibit enhanced fluorescence when doped with inert ligands. This study focuses on a MOF of the UiO-68 structure, which is built from a fluorescent dibenzoate-anthracene ligand doped with a dibenzoate-benzene ligand. Our investigation aims to understand the mechanism behind the doping-enhanced emission of this MOF. We rule out several possible mechanisms, including exciton coupling, electron transfer between ligand and metal center, and ligand intersystem crossing induced by the metal center. Inhibition of the interligand charge transfer is considered a possible way to enhance emission. Furthermore, we propose that the conformational change of the anthracene-based ligand in the MOF cavity is also a way for enhancement. Our molecular dynamics simulations of the MOF structure filled with solvents reveal that the steric crowding in the cavity induces a conformational change at different doping levels, affecting the rate of intersystem crossing of the ligand.


Multifunctional Mitochondrial AAA Proteases.
Mitochondria perform numerous functions necessary for the survival of eukaryotic cells. These activities are coordinated by a diverse complement of proteins encoded in both the nuclear and mitochondrial genomes that must be properly organized and maintained. Misregulation of mitochondrial proteostasis impairs organellar function and can result in the development of severe human diseases. ATP-driven AAA+ proteins play crucial roles in preserving mitochondrial activity by removing and remodeling protein molecules in accordance with the needs of the cell. Two mitochondrial AAA proteases, i-AAA and m-AAA, are anchored to either face of the mitochondrial inner membrane, where they engage and process an array of substrates to impact protein biogenesis, quality control, and the regulation of key metabolic pathways. The functionality of these proteases is extended through multiple substrate-dependent modes of action, including complete degradation, partial processing, or dislocation from the membrane without proteolysis. This review discusses recent advances made toward elucidating the mechanisms of substrate recognition, handling, and degradation that allow these versatile proteases to control diverse activities in this multifunctional organelle.


Liquid-Cell Electron Tomography of Biological Systems.
Liquid-cell electron microscopy is a rapidly growing field in the imaging domain. While real-time observations are readily available to analyze materials and biological systems, these measurementshave been limited to the two-dimensional (2-D) image plane. Here, we introduce an exciting technical advance to image materials in 3-D while enclosed in liquid. The development of liquid-cell electron tomography permitted us to observe and quantify host-pathogen interactions in solution while contained in the vacuum system of the electron microscope. In doing so, we demonstrate new insights for the rules of engagement involving a unique bacteriophage and its host bacterium. A deeper analysis of the genetic content of the phage pathogens revealed structural features of the infectious units while introducing a new paradigm for host interactions. Overall, we demonstrate a technological opportunity to elevate research efforts for in situ imaging while providing a new level of dimensionality beyond the current state of the field.


Diet in the early years of life influences cognitive outcomes at 10 years: a prospective cohort study.
The aim of this study was to investigate the association between diet during the first 3 years of life and cognitive outcomes at 10 years of age. The Raine Study is a longitudinal study of 2868 children and their families. Based on the foods reported to be eaten at age one, two and three, an Eating Assessment in Toddlers diet score was developed, consisting of seven components. Cognition was measured by the Peabody Picture Vocabulary Test-III (PPVT-III) and the Raven's Coloured Progressive Matrices at the 10-year follow-up. Associations were assessed in multivariate regression models. A higher Eating Assessment in Toddlers diet score at age one was associated with higher PPVT-III [β = 0.12 (0.05, 0.19), p = 0.001] and Raven's Coloured Progressive Matrices scores [β = 0.17 (0.02, 0.33), p = 0.025] at age ten after adjustments. Increased fruit consumption at age one was positively associated, while increased sweetened beverage consumption was negatively associated with cognitive development. Dairy consumption at ages two and three had positive associations with the PPVT-III and at age two with the Raven's Coloured Progressive Matrices. A better diet quality during the early years of life may have a positive effect on cognitive ability later in childhood.


Bird communities and biomass yields in potential bioenergy grasslands.
Demand for bioenergy is increasing, but the ecological consequences of bioenergy crop production on working lands remain unresolved. Corn is currently a dominant bioenergy crop, but perennial grasslands could produce renewable bioenergy resources and enhance biodiversity. Grassland bird populations have declined in recent decades and may particularly benefit from perennial grasslands grown for bioenergy. We asked how breeding bird community assemblages, vegetation characteristics, and biomass yields varied among three types of potential bioenergy grassland fields (grass monocultures, grass-dominated fields, and forb-dominated fields), and assessed tradeoffs between grassland biomass production and bird habitat. We also compared the bird communities in grassland fields to nearby cornfields. Cornfields had few birds compared to perennial grassland fields. Ten bird Species of Greatest Conservation Need (SGCN) were observed in perennial grassland fields. Bird species richness and total bird density increased with forb cover and were greater in forb-dominated fields than grass monocultures. SGCN density declined with increasing vertical vegetation density, indicating that tall, dense grassland fields managed for maximum biomass yield would be of lesser value to imperiled grassland bird species. The proportion of grassland habitat within 1 km of study sites was positively associated with bird species richness and the density of total birds and SGCNs, suggesting that grassland bioenergy fields may be more beneficial for grassland birds if they are established near other grassland parcels. Predicted total bird density peaked below maximum biomass yields and predicted SGCN density was negatively related to biomass yields. Our results indicate that perennial grassland fields could produce bioenergy feedstocks while providing bird habitat. Bioenergy grasslands promote agricultural multifunctionality and conservation of biodiversity in working landscapes.


Single-blinded controlled trial of low-dose oral IFN-alpha for the treatment of xerostomia in patients with Sjögren's syndrome.
A single-blinded controlled trial was conducted to test the efficacy of low-dose oral human interferon-alpha (IFN-alpha) to improve salivary function in patients with Sjögren's syndrome. Fifty-six outpatients with primary and 4 patients with secondary Sjögren's syndrome were assigned randomly into treatment groups of either IFN-alpha or sucralfate (control). The IFN-alpha (150 IU) or sucralfate (250 mg) was given orally three times a day for 6 months. Saliva was quantitated monthly by the Saxon test. After 6 months of treatment, 15 of 30 (50%) IFN-alpha-treated patients had saliva production increases at least 100% above baseline, whereas only 1 of 30 (3.3%) sucralfate patients had a comparable increase (p < 0.001). The increase in saliva production, by treatment group, was significantly greater (p < 0.01) in the IFN-alpha treated group at every month after treatment. Serial labial salivary gland biopsies of 9 IFN-alpha responder patients showed that lymphocytic infiltration was significantly decreased (p < 0.02) and the proportion of intact salivary gland tissue was significantly increased (p = 0.004) after the IFN-alpha treatment. In this study, IFN-alpha therapy significantly improved Sjögren's syndrome salivary gland dysfunction.


Arousal, subjective significance and the origin of valence aligned words in the processing of an emotional categorisation task.
An emotional categorisation task allows us to study how emotionality is understood and how emotional factors influence decisions. As emotionality is not only the valence but is also composed of activation (arousal and subjective significance) and the type of process needed to produce emotion (origin), we wanted to test the influence of these emotional factors on with a group of stimuli not differing in valence. We predicted that increasing activation levels should lead to increased classification of stimuli as emotional, with a focus on the late processing stages, when explicit word processing occurs, which on the electrophysiological level corresponds to P300, N450 and LPC components. The behavioural results showed that the emotionality of words increased with increasing levels of arousal and subjective significance. Automatically originated words were assessed as more emotional than reflective ones. The amplitude of the N450 component revealed dissociation for subjective significance and origin effects, showing that these two dimensions ascribe distinct properties of emotionality. Finally, the LPC component was susceptible to all affective dimensions used in manipulation. Our study showed that arousal, subjective significance and origin are dimensions of affect that shape the processing of words' emotionality, when the values of valence were aligned among the stimuli.


[FT, 5-FU and uracil concentrations of the blood, bile and tissue of hepatoma with liver cirrhosis after oral administration of UFT].
UFT was orally administered to eight patients with hepatocellular carcinoma (HCC) combined with liver cirrhosis and to five patients with normal liver. The concentrations of FT-207 (FT), 5-FU, and uracil in blood, tissue and bile were then respectively determined. The FT level in cancer tissue and non-cancer tissue was almost identical in patients with HCC. On the other hand, the 5-FU level in normal liver tissue was significantly higher (P less than 0.05) than that in cancer tissue, and the uracil level in normal liver tissue was lower than that in cancer tissue (P less than 0.05). Transportation of FT from blood to liver was significantly correlated with clearance of indocyanine green from the blood (ICGK). These results suggested that transportation of FT from blood to liver and activation of FT were impaired in HCC with liver cirrhosis. However, the 5-FU level in the cancer tissue of HCC tended to be higher than that in non-cancer tissue. The 5-FU level in the tissue had a significant correlation with the FT level in the tissue. In addition, it was presumed that cancer tissue was able to produce 5-FU from FT more quickly than non-cancer tissue.


The prognostic value of excision repair cross-complementing Group 1 expression in nasopharyngeal cancer patients.
Overexpression of excision repair cross-complementing Group 1 (ERCC-1) is related to cisplatin resistance and defective repair of radiation damage. The purpose of this study was to evaluate the clinical significance of excision (ERCC-1) expression in nasopharyngeal cancer (NPC). We conducted a retrospective review of patients diagnosed with NPC between 2000 and 2013. The archived tissues were analyzed using immunohistochemistry to determine ERCC-1 expression. The ERCC-1 expression level along with other clinical factors and overall survival (OS) were analyzed. Hazard ratio (HR) with a 95% confidence interval was calculated to assess the risk. The analysis of ERCC-1 expression was available in 262 NPC patients who had medical records at our hospital. Among those patients, 221 (84%) were treated with curative radiotherapy (RT)/concurrent chemoradiotherapy, 22 (7%) were treated with palliative RT alone, and 19 (9%) were given best supportive care. There was no correlation between ERCC-1 expression and stage of cancer or OS. No difference in 5-year OS was found between patients with low ERCC-1 expression and high ERCC-1 expression (38% vs. 36%; P = 0.981). The adjusted HR (aHR) of cancer death increased with cancer stage (aHR = 2.93 for advanced Stages III-IV; P = 0.001) and age (aHR = 2.11 for age >55; P ≤ 0.001). ERCC-1 expression exhibited no prognostic significance in our study (aHR = 1). In this study, ERCC-1 expression has no statistical significance to be considered a prognostic factor for OS among NPC patients. On the other hand, cancer stage, age, and types of treatment can be prognostic factors in NPC patients.


Exposure Marker Discovery of Phthalates Using Mass Spectrometry.
Phthalates are chemicals widely used in industry and the consequences on human health caused by exposure to these agents are of significant interest currently. The urinary metabolites of phthalates can be measured and used as exposure markers for the assessment of the actual internal contamination of phthalates coming from different sources and absorbed by various ways. The purpose of this paper is to review the markers for exposure and risk assessment of phthalates such as di-methyl phthalate (DMP), di-ethyl phthalate (DEP), di-butyl phthalate (DBP), benzylbutyl phthalate (BBP), di-(2-ethylhexyl)phthalate (DEHP), di-(2-propylheptyl)phthalate (DPHP), di-iso-nonyl phthalate (DINP), di-n-octyl phthalate (DnOP) and di-iso-decyl phthalate (DIDP), and introduction of the analytical approach of three metabolomics data processing approaches that can be used for chemical exposure marker discovery in urine with high-resolution mass spectrometry (HRMS) data.


Combat damage control surgery.
Although the use of damage control surgery for blunt and penetrating injury has been widely reported and defined, the use of damage control surgery on the battlefield (combat damage control surgery) has not been well detailed. Damage control surgery is now well established as the standard of care for severely injured civilian patients requiring emergent laparotomy in the United States. The civilian damage control paradigm is based on a "damage control trilogy." This trilogy comprises an abbreviated operation, intensive care unit resuscitation, and a return to the operating room for the definitive operation. The goal of damage control surgery and the triology is avoidance of irreversible physiological insult termed the lethal triad. The lethal triad comprises the vicious cycle of hypothermia, acidosis, and coagulopathy. Although the damage control model involves the damage control trilogy, abbreviated operation, intensive care unit resuscitation, and definitive operation, all in the same surgical facility, the combat damage control paradigm must incorporate global evacuation through several military surgical facilities and involves up to ten stages to allow for battlefield evacuation, surgical operations, multiple resuscitations, and transcontinental transport. Combat damage control surgery represents many unique challenges for those who care for the severely injured patients in a combat zone.


[Advances in neuromodulation of pulmonary hypertension].
Pulmonary hypertension is a progressive disease characterized by an increase in pulmonary vascular resistance, leading to unfavorable pulmonary vascular remodeling. This condition eventually leads to right ventricular hypertrophy and ultimately death from right ventricular failure. Although the exact pathogenesis of pulmonary hypertension remains unclear, autonomic nervous system dysfunction is recognized as one of the contributing factors. Increasing evidence supports the hypothesis that activation of the sympathetic nervous system plays a role in the development of pulmonary hypertension. In addition, pulmonary artery denervation has shown some effectiveness in the treatment of this condition. This article provides a comprehensive review of the neuroanatomical basis of the pulmonary vessels, the potential mechanisms underlying the onset and progression of pulmonary hypertension in relation to neuromodulation, and the application of neuromodulation techniques in its treatment.


Stereotyped neuropil branching of an identified stomatogastric motor neuron.
Anatomical studies of the crab stomatogastric ganglion (STG) have suggested only minimal organization within the neuropil of this structure. Here, we present evidence that, for at least one intrinsic neuron type, the ventricular dilator (VD) neuron, a highly organized and stereotyped branching structure exists within the stomatogastric neuropil. Specifically, we show the morphology of the VD neuron consists of a single primary neurite that projects from the soma into the neuropil and bifurcates into a pair of subprimary neurites, which in turn exit the neuropilar region, one entering the left and the other the right medial ventricular nerve. Nearly all secondary neurite branching of the VD neuron is from the subprimary neurites. There are approximately 22 secondary branches/neuron (range 14-28), with no significant difference between the number of secondary branches off the right vs. the left subprimary neurite, although the ratio of secondary branches between subprimaries varies (range 0.4-1.6). The fine neurites that branch from the secondary processes segregate hemispherically within the neuropil, based on the subprimary neurite of origin. Within this hemispherical organization, another level of fine neurite segregation is present, namely, the fine neurites derived from each secondary branch are restricted to discrete regions of the hemisphere with only minimal overlap with those derived from other secondary branches. Monte Carlo simulations show that this segregation differs significantly from a random distribution. The organization of branching seen in the VD neuron may play a critical role in the electrotonic and local computational organization of this neuron and sets the stage for physiological experimentation addressing these issues.


Envelope-bound N-acetylmuramyl-L-alanine amidase of Escherichia coli K 12. Purification and properties of the enzyme.
N-Acetylmuramyl-L-alanine amidase activity was detected in Escherichia coli K 12 by usine N-acetylmuramyl-L-alanyl-gamma-D-glutamyl-(L)-meso-[3H]diaminopimelic acid as a radioactive substrate. This activity cleaves the amide bond between the residues of N-acetylmuramyl acid and L-alanine. It was readily obtained in a soluble form either by mechanical disruption of the cells or by spheroplast formation. In the latter case the release of most of the activity into the sucrose medium seems to indicate that it is either periplasmic or associated with the outer membrane of the envelope of E. coli K 12. The enzyme was purified to near homogeneity. A molecular weight of 39 000 was determined by gel filtration and confirmed by polyacrylamide gel electrophoresis. Further characterisation of this N-acetylmuramyl-L-alanine amidase activity was carried out by investigating several of its properties.


Reactivation of occult HBV infection in an HIV/HCV Co-infected patient successfully treated with sofosbuvir/ledipasvir: a case report and review of the literature.
Reactivation of occult or inactive Hepatitis B virus (HBV) infection during immunosuppressant treatments is well known and widely described in literature. The same observation has been made in Hepatitis C (HCV)-infected patients previously exposed to HBV and treated with interferon-free DAA treatments. Because of common transmission routes, persons may have been exposed to HCV, HBV and HIV, but few cases have been reported in this scenario to date. Frequency of HBV reactivation in HIV/HCV co-infected patients previously exposed to HBV and treated with DAA remains unclear. Herein, we report an episode of HBV reactivation in an HIV/HCV co-infected patient prescribed with sofosbuvir/ledipasvir for HCV. The patient is a Caucasian 54-years old female, with HIV/HCV co-infection (genotype 4), and a previous exposure to HBV, documented by negativity of HBsAg and positivity of HBsAb and HBcAb. Her medical history included: myocardial infarct, chronic kidney disease stage 3, chronic obstructive pulmonary disease, and mild pulmonary hypertension. HCV had not been treated with interferon (IFN)-based regimens and liver stiffness was 10.5 KPa (Metavir stage F3) at hepatic elastography. Because of CKD, she was prescribed with a nucleoside reverse transcriptase (NRTI)-sparing regimen including darunavir/ritonavir plus etravirine, and thereafter with sofosbuvir/ledipasvir for 12 weeks. Four weeks after DAA termination, the patient was hospitalized with symptoms of acute hepatitis. Blood tests showed HCV RNA <12 IU/ml, but positivity of HBAg, HBeAg, and of anti-core antibodies (IgM and IgG), while anti-HBs and anti-HBe antibodies were negative. HBV DNA was 6.06 Log10 IU/ml. Entecavir was started obtaining resolution of symptoms, normalization of liver enzymes, as well as reduction of HBV DNA and of quantitative HBV surface antigen. This case-report highlights the risk of HBV reactivation with interferon-free DAA treatment in HIV/HCV co-infected patients previously exposed to HBV and who have contraindications for treatment with nucleoside/nucleotide reverse transcriptase Inhibitors because of comorbid conditions. In the setting of HIV infection, clinicians prescribing DAA should be aware of this risk, and HBV assessment at treatment start as well as virological monitoring during DAA treatment is recommended. Large epidemiological and virological studies are needed to investigate reactivation of occult HBV infection more in depth.


NHLBI plans for the promise of cell-based therapies.
This article presents the National Heart, Lung and Blood Institute (NHLBI) perspective on the status of cell-based therapies. A summary of current and future NHLBI/National Institutes of Health (NIH) programs is given along with a history of the development of NHLBI/NIH resources to aid the advancement of cell-based therapies. A brief discussion of clinical research programs to utilize cell-based therapies is also included.


Performance optimization in two-dimensional Brownian rotary ratchet models.
With a model for two-dimensional (2D) Brownian rotary ratchets being capable of producing a net torque under athermal random forces, its optimization for mean angular momentum (L), mean angular velocity (ω), and efficiency (η) is considered. In the model, supposing that such a small ratchet system is placed in a thermal bath, the motion of the rotor in the stator is described by the Langevin dynamics of a particle in a 2D ratchet potential, which consists of a static and a time-dependent interaction between rotor and stator; for the latter, we examine a force [randomly directed dc field (RDDF)] for which only the direction is instantaneously updated in a sequence of events in a Poisson process. Because of the chirality of the static part of the potential, it is found that the RDDF causes net rotation while coupling with the thermal fluctuations. Then, to maximize the efficiency of the power consumption of the net rotation, we consider optimizing the static part of the ratchet potential. A crucial point is that the proposed form of ratchet potential enables us to capture the essential feature of 2D ratchet potentials with two closed curves and allows us to systematically construct an optimization strategy. In this paper, we show a method for maximizing L, ω, and η, its outcome in 2D two-tooth ratchet systems, and a direction of optimization for a three-tooth ratchet system.


Nutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents: risk for UTT in children exposed to melamine-contaminated milk formulas.
Urinary tract tumors are tenth in frequency, and many environmental carcinogens are excreted by urine. Interplay between chronic inflammatory urolithiasis and urothelial carcinogenesis is not well understood. Experimental evidences show that dietary melamine induce these events even at low concentrations. This is important because thousands of children were exposed to melamine through intentionally contaminated milk formula worldwide. We propose that an increased risk for urinary tumors in adult life may occur and screenings for early urinary signs may be necessary. Therefore, urothelial biology, melamine carcinogenic potential, and related epidemiology are discussed, recommending a preventive dietary polyunsaturated fatty acid-based supplementation, since they modulate such interplay in rodents.