Testosterone therapy and obstructive sleep apnea: is there a real connection?
With the recent increased recognition and treatment of hypogonadism in men, a caution has been given that testosterone replacement therapy (TRT) may cause or aggravate obstructive sleep apnea syndrome (OSA). To evaluate the scientific data behind the cautionary statements about TRT and OSA. Methodology and criteria for such studies and evaluation of documents and results based on methodology, duration, and outcome of treatment. A review of the literature on the subject of TRT and OSA was performed. The possible mechanisms of action of TRT, on breathing and respiration during sleep were explored. Historically, the first such caution came in 1978. Since then, a few similar incidence reports have been cited. The total number of patients in such reports was very small, very disproportional to the millions of patients treated with TRT. Also, there was a lack of consistent findings connecting TRT to OSA. In addition, different results may occur with physiologic replacement vs. supraphysiologic doses in regard to breathing and OSA. The studies showing the effect of TRT on OSA and breathing were all case studies with small numbers of subjects and showed little effect of TRT on OSA in the majority of case reports. Only one study using supraphysiologic doses was a double-blind, placebo-controlled study, which showed a development of OSA in healthy pooled subjects. The other reports were case studies with limited numbers of subjects, suggesting an inconsistent effect of supraphysiologic TRT on OSA and breathing. Cautionary statements about TRT in OSA appear frequently in the TRT literature and guidelines, despite lack of convincing evidence that TRT causes and/or aggravates OSA. Also, there is a lack of consistency in the findings connecting TRT to OSA. It is evident that the link between TRT and OSA is weak, based on methodological issues in many of the studies, and most studies involved small numbers of men. Further studies in this area are needed.


Enhanced presentation of major histocompatibility complex class I-restricted human immunodeficiency virus type 1 (HIV-1) Gag-specific epitopes after DNA immunization with vectors coding for vesicular stomatitis virus glycoprotein-pseudotyped HIV-1 Gag particles.
In vivo priming of cytotoxic T lymphocytes (CTL) by DNA injection predominantly occurs by antigen transfer from DNA-transfected cells to antigen-presenting cells. A rational strategy for increasing DNA vaccine potency would be to use a delivery system that facilitates antigen uptake by antigen-presenting cells. Exogenous antigen presentation through the major histocompatibility complex (MHC) class I-restricted pathway of some viral antigens is increased after adequate virus-receptor interaction and the fusion of viral and cellular membranes. We used DNA-based immunization with plasmids coding for human immunodeficiency virus type 1 (HIV-1) Gag particles pseudotyped with vesicular stomatitis virus glycoprotein (VSV-G) to generate Gag-specific CTL responses. The presence of the VSV-G-encoding plasmid not only increased the number of mice displaying anti-Gag-specific cytotoxic response but also increased the efficiency of specific lysis. In vitro analysis of processing confirmed that exogenous presentation of Gag epitopes occurred much more efficiently when Gag particles were pseudotyped with the VSV-G envelope. We show that the VSV-G-pseudotyped Gag particles not only entered the MHC class II processing pathway but also entered the MHC class I processing pathway. In contrast, naked Gag particles entered the MHC class II processing pathway only. Thus, the combined use of DNA-based immunization and nonreplicating pseudotyped virus to deliver HIV-1 antigen to the immune system in vivo could be considered in HIV-1 vaccine design.


Transferrin-directed preparation of red-emitting copper nanoclusters for targeted imaging of transferrin receptor over-expressed cancer cells.
Transferrin (Trf)-functionalized copper nanoclusters (Trf-Cu NCs) were fabricated as a novel red-emitting fluorescent probe for the targeted bioimaging of cancer cells. A one-pot approach was developed to prepare stable, water-soluble and red-emitting Trf-Cu NCs at room temperature via a biomineralization process with Trf as the template and ascorbic acid as a green reducing agent. Trf acted not only as a stabilizer and reducer, but also as a functional ligand for targeting the transferrin receptor. The as-prepared Trf-Cu NCs showed an intense red fluorescence with a red emission peak at 670 nm (quantum yield about 6.2%), suggesting that the probe could potentially be used for bioimaging in vivo. The developed Trf-Cu NCs had excellent photostability and water solubility and exhibited a high specificity to transferrin receptor with negligible cytotoxicity. The probe was successfully applied to the targeted bioimaging of HeLa cells.


Physical Activity on Prescription (PAP), in patients with metabolic risk factors. A 6-month follow-up study in primary health care.
There is strong evidence that inadequate physical activity (PA) leads to an increased risk of lifestyle-related diseases and premature mortality. Physical activity on prescription (PAP) is a method to increase the level of PA of patients in primary care, but needs further evaluation. The aim of this observational study was to explore the association between PAP-treatment and the PA level of patients with metabolic risk factors and the relationship between changes in the PA level and health outcomes at the 6 month follow-up. This study included 444 patients in primary care, aged 27-85 years (56% females), who were physically inactive with at least one component of metabolic syndrome. The PAP-treatment model included: individualized dialogue concerning PA, prescribed PA, and a structured follow-up. A total of 368 patients (83%) completed the 6 months of follow-up. Of these patients, 73% increased their PA level and 42% moved from an inadequate PA level to sufficient, according to public health recommendations. There were significant improvements (p≤ 0.05) in the following metabolic risk factors: body mass index, waist circumference, systolic blood pressure, fasting plasma glucose, cholesterol, and low density lipoprotein. There were also significant improvements regarding health-related quality of life, assessed by the Short Form 36, in: general health, vitality, social function, mental health, role limitation-physical/emotional, mental component summary, and physical component summary. Regression analysis showed a significant association between changes in the PA level and health outcomes. During the first 6-month period, the caregiver provided PAP support 1-2 times. This study indicates that an individual-based model of PAP-treatment has the potential to change people's PA behavior with improved metabolic risk factors and self-reported quality of life at the 6 month follow-up. Thus, PAP seems to be feasible in a clinical primary care practice, with minimum effort from healthcare professionals.


Intrinsic multiferroics in an individual single-crystalline Bi5Fe0.9Co0.1Ti3O15 nanoplate.
In recent years, much attention has been paid to layer-structured Bi4Bim-3Fem-3-xMxTi3O3m+3 (BFMTO, M = Co, Mn) compounds due to their potential as high temperature single phase multiferroic materials. However, BFMTO single crystals have been rarely reported in the past, though they are better candidates for studying the corresponding intrinsic multiferroics as well as the platform for making future devices, due to their structural complexity and difficulties in fabrication. In this article, Bi5Fe0.9Co0.1Ti3O15 single-crystalline nanoplates were synthesized by the hydrothermal method. The ferromagnetic domain structure of the nanoplate was investigated by electron holography. Denser phase contours were observed and the closed magnetic flux lines indicated a significant magnetic interaction between the neighboring nanoplates, which proved the ferromagnetic nature of the sample. Furthermore, M-H loops of the sample were also measured, in which the ferromagnetic Curie temperature reached ∼730.2 K. Besides, ferroelectric domains were also detected by using a piezoresponse force microscope. All the above-mentioned results indicate the first verification of the room temperature (RT) multiferroic behaviour in such single crystals, which will be useful for both future devices and understanding the underlining physics.


[Preservation of microorganisms by deep freezing].
Meningococci, pneumococci, and hemophilic bacilli may be stored at -70 degrees C. Only half (54.4 percent) of Meningococcal cultures were viable after 11 months storage, 41.6 percent retained their serologic properties. Conditions for stable long storage of meningococci at -70 degrees C are to be searched for. Pneumococci retained their initial parameters for 8 months, this permitting recommendation of such storage for these bacteria. No data on the possibility of hemophilic bacilli storage is available yet.


Partner switching mechanisms in inactivation and rejuvenation of Escherichia coli DNA gyrase by F plasmid proteins LetD (CcdB) and LetA (CcdA).
Escherichia coli DNA gyrase, as well as a free form of its A subunit (GyrA), exists in an inactivated form in cells that overproduce the F plasmid protein LetD (CcdB). We found that the inactivated DNA gyrase and GyrA protein can be rejuvenated in vitro by another F plasmid protein, LetA (CcdA). Using this rejuvenation as an assay, we purified the inactivated GyrA protein to near homogeneity and found it to be complexed with the LetD protein. The complex has a molecular mass of 230 kDa and was suggested to be a complex of two molecules each of GyrA and LetD proteins. The GyrA-LetD complex, in the presence of purified GyrB protein, does not cause DNA cleavage. Therefore, the LetD protein in the GyrA-LetD complex inhibits the gyrase action by a mechanism different from one that involves trapping a covalently linked gyrase-DNA complex. In as much as a free form of the LetD protein has been shown to induce DNA cleavage by gyrase, the LetD protein seems to have two distinct modes of action on DNA gyrase. Rejuvenation of the inactivated GyrA protein by the LetA protein was achieved in vitro, and mechanisms governing this process were examined using the purified proteins. The rejuvenated GyrA protein sediments through sucrose gradients as a single protein species of 190 kDa and is indistinguishable from a free form of GyrA protein. In the same sedimentation experiment, the LetD protein was seen to be complexed with the added LetA protein. Thus, the LetA protein apparently rejuvenates the GyrA protein by removing the bound LetD protein from the inactivated form, followed by formation of a LetA-LetD complex.


To Assess Whether Lee's Grading System for Central Lumbar Spinal Stenosis Can Be Used as a Decision-Making Tool for Surgical Treatment.
To evaluate the correlation between Lee's grades and surgical intervention for central lumbar spinal stenosis (CLSS) and to assess whether this grading system can be used as a decision-making tool for the surgical treatment of this condition. This retrospective study included 290 patients (M:F = 156:134; mean age, 46 ± 16 years). Radiologists assessed the presence and grade of CLSS at the stenosis point according to Lee's grading system, in which CLSS is classified into four grades according to the shape of the cauda equina. Correlation coefficients (rs ) between Lee's grades and the operation were calculated with Spearman rank correlation. Among the operated patients, grade 2 was the most commonly assigned grade (50%-58%), grade 3 was less common (35%), and grade 0 was the least common (2%-3%). Among the non-operated patients, grade 1 was the most common (63%-65%), grade 0 was less common (15%-16%), and grade 3 was the least common (8%). The distribution of grades differed between the operated and non-operated groups (p < 0.001). Less than 25% of patients who underwent surgery were assigned grades 0 and 1, and more than 88% were assigned grades 2 and 3. A moderate correlation was found between the grade and surgical intervention (rs = 0.632 and rs = 0.583). Lee's grade was moderately correlated with surgical intervention. Lee's grading system can be a decision-making tool for the surgical treatment of CLSS.


Mega-impact formation of the Mars hemispheric dichotomy.
The Mars hemispheric dichotomy is expressed as a dramatic difference in elevation, crustal thickness and crater density between the southern highlands and northern lowlands (which cover approximately 42% of the surface). Despite the prominence of the dichotomy, its origin has remained enigmatic and models for its formation largely untested. Endogenic degree-1 convection models with north-south asymmetry are incomplete in that they are restricted to simulating only mantle dynamics and they neglect crustal evolution, whereas exogenic multiple impact events are statistically unlikely to concentrate in one hemisphere. A single mega-impact of the requisite size has not previously been modelled. However, it has been hypothesized that such an event could obliterate the evidence of its occurrence by completely covering the surface with melt or catastrophically disrupting the planet. Here we present a set of single-impact initial conditions by which a large impactor can produce features consistent with the observed dichotomy's crustal structure and persistence. Using three-dimensional hydrodynamic simulations, large variations are predicted in post-impact states depending on impact energy, velocity and, importantly, impact angle, with trends more pronounced or unseen in commonly studied smaller impacts. For impact energies of approximately (3-6) x 10(29) J, at low impact velocities (6-10 km s(-1)) and oblique impact angles (30-60 degrees ), the resulting crustal removal boundary is similar in size and ellipticity to the observed characteristics of the lowlands basin. Under these conditions, the melt distribution is largely contained within the area of impact and thus does not erase the evidence of the impact's occurrence. The antiquity of the dichotomy is consistent with the contemporaneous presence of impactors of diameter 1,600-2,700 km in Mars-crossing orbits, and the impact angle is consistent with the expected distribution.


Binding of low molecular weight inhibitors promotes large conformational changes in the dengue virus NS2B-NS3 protease: fold analysis by pseudocontact shifts.
The two-component dengue virus NS2B-NS3 protease (DEN NS2B-NS3pro) is an established drug target, but inhibitor design is hampered by the lack of a crystal structure of the protease in its fully active form. In solution and without inhibitors, the functionally important C-terminal segment of the NS2B cofactor is dissociated from DEN NS3pro ("open state"), necessitating a large structural change to produce the "closed state" thought to underpin activity. We analyzed the fold of DEN NS2B-NS3pro in solution with and without bound inhibitor by nuclear magnetic resonance (NMR) spectroscopy. Multiple paramagnetic lanthanide tags were attached to different sites to generate pseudocontact shifts (PCS). In the face of severe spectral overlap and broadening of many signals by conformational exchange, methods for assignment of (15)N-HSQC cross-peaks included selective mutation, combinatorial isotope labeling, and comparison of experimental PCSs and PCSs back-calculated for a structural model of the closed conformation built by using the structure of the related West Nile virus (WNV) protease as a template. The PCSs show that, in the presence of a positively charged low-molecular weight inhibitor, the enzyme assumes a closed state that is very similar to the closed state previously observed for the WNV protease. Therefore, a model of the protease built on the closed conformation of the WNV protease is a better template for rational drug design than available crystal structures, at least for positively charged inhibitors. To assess the open state, we created a binding site for a Gd(3+) complex and measured paramagnetic relaxation enhancements. The results show that the specific open conformation displayed in the crystal of DEN NS2B-NS3pro is barely populated in solution. The techniques used open an avenue to the fold analysis of proteins that yield poor NMR spectra, as PCSs from multiple sites in combination with model building generate powerful information even from incompletely assigned (15)N-HSQC spectra.


Comparative permeability of different glioma models to horseradish peroxidase.
Seven different experimental glioma models were studied to determine their capillary permeability to horseradish peroxidase. The models were the autochthonous ASV-viral model, intracerebral (ic) and (sc) injections of rat 9L and RG-2 tumor cell lines, the sc rat S-69C15 tumor cell line, and human glioblastoma cell lines in nude mice. The ASV-viral model showed an average HRP permeability of 63% of tumor volume, the ic RG-2 tumors were 100% permeable, and the ic 9L tumors were 41% permeable. The permeability of the marginal zone (brain-tumor interface) showed similar variation from group to group. In contrast, all of the sc tumors were 100% permeable regardless of the cell line used to create the tumors. Our results show the variability between these glioma models, and suggest that RG-2 ic gliomas and all sc gliomas should be optimal to assess the tumoricidal effect of drugs, because access to the tumor compartment from the vascular compartment is complete.


A Fistula Where? Left Anterior Descending to Pulmonary Artery Fistula.
Fistulas are abnormal passageways between two organs or vessels that usually do not connect. Coronary artery fistulas occur when one of the coronary arteries is connected to either a heart chamber or another blood vessel. This case presents a coronary artery fistula which may or may not be impacting the patient's heart function. A 69-year-old male with multiple comorbidities presents with a chief complaint of shortness of breath. Catheterization reveals an anomalous left anterior descending to pulmonary artery fistula without a step up in oxygen saturation at the level of the pulmonary artery. Surgical management was deferred as this fistula was not deemed to contribute to the patient's declining cardiac function. Operative management versus embolization would be a feasible alternative for patients who are symptomatic secondary to the coronary artery fistula and remains to be controversial in patients who are asymptomatic. Given the possibility of these fistulae eventually causing symptoms it would be practical to close them early on before symptoms arise or before size of the fistulae becomes an issue. Further research should be conducted to understand the management strategies for patients who present with coronary artery fistulas.


KASP: a genotyping method to rapid identification of resistance in Plasmodium falciparum.
The emergence and spread of anti-malarial resistance continues to hinder malaria control. Plasmodium falciparum, the species that causes most human malaria cases and most deaths, has shown resistance to almost all known anti-malarials. This anti-malarial resistance arises from the development and subsequent expansion of Single Nucleotide Polymorphisms (SNPs) in specific parasite genes. A quick and cheap tool for the detection of drug resistance can be crucial and very useful for use in hospitals and in malaria control programmes. It has been demonstrated in different contexts that genotyping by Kompetitive Allele Specific PCR (KASP), is a simple, fast and economical method that allows a high-precision biallelic characterization of SNPs, hence its possible utility in the study of resistance in P. falciparum. Three SNPs involved in most cases of resistance to the most widespread anti-malarial treatments have been analysed by PCR plus sequencing and by KASP (C580Y of the Kelch13 gene, Y86N of the Pfmdr1 gene and M133I of the Pfcytb gene). A total of 113 P. falciparum positive samples and 24 negative samples, previously analysed by PCR and sequencing, were selected for this assay. Likewise, the samples were genotyped for the MSP-1 and MSP-2 genes, and the Multiplicity of Infection (MOI) and parasitaemia were measured to observe their possible influence on the KASP method. The KASP results showed the same expected mutations and wild type genotypes as the reference method, with few exceptions that correlated with very low parasitaemia samples. In addition, two cases of heterozygotes that had not been detected by sequencing were found. No correlation was found between the MOI or parasitaemia and the KASP values of the sample. The reproducibility of the technique shows no oscillations between repetitions in any of the three SNPs analysed. The KASP assays developed in this study were efficient and versatile for the determination of the Plasmodium genotypes related to resistance. The method is simple, fast, reproducible with low cost in personnel, material and equipment and scalable, being able to core KASP arrays, including numerous SNPs, to complete the main pattern of mutations associated to P. falciparum resistance.


Acute Pancreatitis Secondary to Dengue Fever: An Uncommon Presentation of a Common Endemic Illness.
Dengue viral infection is considered endemic in Ecuador. It is more frequent during winter, caused by an RNA virus in the Flavivirus group. Its presentation can range from an asymptomatic state to hemorrhagic fever with shock signs. Acute pancreatitis could be a rare form of acute abdomen presentation associated with dengue virus infection. This case illustrates a 26-year-old man who presents to the hospital with cramp-like pain in the epigastrium and radiation to the right upper quadrant, accompanied by nausea and vomiting. He also endorsed additional symptoms such as throbbing-like headache, myoarthralgias, and fever of 40.4°C (104.72°F). Laboratory tests revealed elevated hematocrit, thrombocytopenia, elevated pancreatic enzymes, transaminitis, elevated alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT). Ultrasonography of the abdomen revealed hepatic steatosis, free fluid in the abdominal cavity, and small bilateral pleural effusions. Additional testing revealed IgM and IgG antibodies positivity to dengue virus. The patient was treated conservatively with intravenous (IV) fluid hydration and bowel rest. Acute pancreatitis should be considered when a patient presents with a suspected acute abdomen in the emergency department, and a detailed medical history is necessary to make a correct approach to the differential diagnosis.


Two-dimensional vocal tracts with three-dimensional behavior in the numerical generation of vowels.
Two-dimensional (2D) numerical simulations of vocal tract acoustics may provide a good balance between the high quality of three-dimensional (3D) finite element approaches and the low computational cost of one-dimensional (1D) techniques. However, 2D models are usually generated by considering the 2D vocal tract as a midsagittal cut of a 3D version, i.e., using the same radius function, wall impedance, glottal flow, and radiation losses as in 3D, which leads to strong discrepancies in the resulting vocal tract transfer functions. In this work, a four step methodology is proposed to match the behavior of 2D simulations with that of 3D vocal tracts with circular cross-sections. First, the 2D vocal tract profile becomes modified to tune the formant locations. Second, the 2D wall impedance is adjusted to fit the formant bandwidths. Third, the 2D glottal flow gets scaled to recover 3D pressure levels. Fourth and last, the 2D radiation model is tuned to match the 3D model following an optimization process. The procedure is tested for vowels /a/, /i/, and /u/ and the obtained results are compared with those of a full 3D simulation, a conventional 2D approach, and a 1D chain matrix model.


Impact of female daily coffee consumption on successful fertility treatment: a Danish cohort study.
To investigate whether female coffee consumption affects the chance of achieving a clinical pregnancy and a live birth among women and couples receiving medically assisted reproduction (MAR) treatment. Cohort study with prospectively collected exposure data. Public fertility clinic. A total of 1,708 women and potential partners undergoing fertility treatment, contributing with 1,511 intrauterine insemination (IUI) cycles, 2,870 in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles, and 1,355 frozen embryo transfer cycles. None. Clinical pregnancy and live birth in consecutive treatment cycles in the Danish national health registries, enabling complete follow-up, and estimation of the cumulative chance of live birth for three consecutive treatment cycles. Among women receiving IVF or ICSI treatment, coffee consumption did not seem to affect the chance of achieving a clinical pregnancy and a live birth. Women treated with IUI who had a daily coffee consumption of 1-5 cups were more likely to achieve a clinical pregnancy (adjusted relative risk 1.49; 95% confidence interval, 1.05-2.11) and live birth (adjusted relative risk 1.53; 95% confidence interval, 1.06-2.21) compared with the reference group of coffee abstainers. Women consuming 1-5 cups versus none had a 1.5-fold higher probability of achieving a pregnancy or a live birth when receiving IUI. No associations were found, however, between women's daily coffee consumption and achieving a pregnancy or a live birth from IVF/ICSI.


Association of perioperative blood transfusion with oncologic outcomes after radical nephroureterectomy for upper tract urothelial carcinoma.
To test the hypothesis that perioperative blood transfusion (PBT)impacts oncologic outcomes of patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Retrospective analysis of 2492 patients with UTUC treated at 23 institutions with RNU between 1987 and 2007.Cox regression models addressed the association of PBT with disease recurrence, cancer-specific mortality and any-cause mortality. A total of 510 patients (20.5%) patients received PBT. Within a median follow-up of 36 months (Interquartile range: 55 months), 663 (26.6%) patients experienced disease recurrence, 545 patients (21.9%) died of UTUC and 884 (35.5%) patients died from any cause. Patients who received PBT were at significantly higher risk of disease recurrence, cancer-specific mortality and overall mortality than patients not receiving PBT in univariable Cox regression analyses. In multivariable Cox regression analyses that adjusted for the effects of standard clinicopathologic features, PBT did not remain associated with disease recurrence (HR: 1.11; 95% CI 0.92-1.33, p = 0.25), cancer-specific mortality (HR: 1.09; 95% CI 0.89-1.33, p = 0.41) or overall mortality (HR: 1.09; 95% CI 0.93-1.28, p = 0.29). In patients undergoing RNU for UTUC, PBT is associated with disease recurrence, cancer-specific survival or overall survival in univariable, but not in multivariable Cox regression analyses.


PERK activation preserves the viability and function of remyelinating oligodendrocytes in immune-mediated demyelinating diseases.
Remyelination occurs in multiple sclerosis (MS) lesions but is generally considered to be insufficient. One of the major challenges in MS research is to understand the causes of remyelination failure and to identify therapeutic targets that promote remyelination. Activation of pancreatic endoplasmic reticulum kinase (PERK) signaling in response to endoplasmic reticulum stress modulates cell viability and function under stressful conditions. There is evidence that PERK is activated in remyelinating oligodendrocytes in demyelinated lesions in both MS and its animal model, experimental autoimmune encephalomyelitis (EAE). In this study, we sought to determine the role of PERK signaling in remyelinating oligodendrocytes in MS and EAE using transgenic mice that allow temporally controlled activation of PERK signaling specifically in oligodendrocytes. We demonstrated that persistent PERK activation was not deleterious to myelinating oligodendrocytes in young, developing mice or to remyelinating oligodendrocytes in cuprizone-induced demyelinated lesions. We found that enhancing PERK activation, specifically in (re)myelinating oligodendrocytes, protected the cells and myelin against the detrimental effects of interferon-γ, a key proinflammatory cytokine in MS and EAE. More important, we showed that enhancing PERK activation in remyelinating oligodendrocytes at the recovery stage of EAE promoted cell survival and remyelination in EAE demyelinated lesions. Thus, our data provide direct evidence that PERK activation cell-autonomously enhances the survival and preserves function of remyelinating oligodendrocytes in immune-mediated demyelinating diseases.


Salvage surgery for bulky local recurrence of prostate cancer following radical prostatectomy.
We report our experience with salvage radical surgery as palliative treatment in patients with bulky recurrence of prostate cancer following radical prostatectomy (RP). From files at the department of urology we identified 5 patients who had biopsy confirmed, bulky recurrence of prostate cancer after initial RP and subsequent salvage radiation therapy (4), prior to presentation at our cancer center. Positive surgical margins were present in all 5 patients. All received androgen ablation and 4 also received systemic chemotherapy. Due to persistent bulky tumors in the 5 patients and debilitating unrelenting symptoms, including refractory hematuria, obstructive uropathy and pelvic pain in 4, salvage radical surgery was performed. Total pelvic exenteration was done in 4 patients and wide tumor resection with continent urinary diversion was done in 1. Four patients were permanently relieved of local symptoms following surgery and another had entero-urethral fistula formation. Revision of a continent urinary diversion was necessary in another patient who was otherwise free of cancer and of local pelvic symptoms. Long-term symptom-free survival was achieved in 2 patients following surgery at 26 and 56 months, respectively. One patient died of metastatic disease 3.5 months after surgery but he had been rendered free of local symptoms by surgery. The other 2 patients are currently free of local symptoms 5 and 7 months following surgery, respectively. Wound infection, delirium and prolonged ileus occurred in 1 patient each. Otherwise surgery was well tolerated. Salvage radical surgery is feasible and it provides effective palliation in patients with bulky local recurrence following RP.


Ketogenic Metabolism Inhibits Histone Deacetylase (HDAC) and Reduces Oxidative Stress After Spinal Cord Injury in Rats.
The aim of this study is to investigate the effect of ketogenic metabolism, induced by different diet interventions, on histone acetylation and its potential antioxidant capacity to injured spinal cord tissue in rats. 72 male Sprague-Dawley rats were randomly divided into 4 groups, fed with ketogenic diet (KD), every other day fasting (EODF), every other day ketogenic diet (EODKD) and standard diet (SD) respectively for 2 weeks. β-Hydroxybutyrate (βOHB) concentration was measured both in serum and cerebrospinal fluid (CSF). C5 spinal cord tissue was harvested before, at 3 h and 24 h after injury for analysis of HDAC activity, histone acetylation and oxidative makers. All three dietary interventions resulted in a significant increase of βOHB level in both serum and CSF, and inhibited HDAC activity by 31-43% in spinal cord. Moreover, the expressions of acetylated histone AcH3K9 and AcH3K14 were significantly increased. Anti-oxidative stress genes Foxo3a and Mt2 and related proteins, such as mitochondrial superoxide dismutase (SOD), FOXO3a, catalase were increased in dietary intervention groups. After SCI, high ketogenic metabolism demonstrated significant reduction of the expression of lipid peroxidation factors malondialdehyde (MDA), and this might contribute to the reported neuroprotection of the spinal cord from oxidative damage possibly mediated by increasing SOD. The result of this study suggested that by inhibiting HDAC activity and modifying related gene transcription, ketogenic metabolism, induced by KD, EODF or EODKD, might reduce oxidative damage in the spinal cord tissue after acute injury.


Reliability and validity of the Yoruba version of the Oswestry disability index.
Low back pain (LBP) is a major cause of disability, and the Oswestry Disability Index (ODI) is a validated assessment tool for evaluating disability in LBP patients. Cross-cultural adaptation of the ODI is important because not all populations are proficient in English. The Yoruba language is an indigenous language spoken by 40 million people in the Western part of Nigeria and some countries in West Africa and Latin America. Currently, no validated Yoruba version of ODI is available. The aim of the study was to translate, culturally adapt and validate the ODI in Yoruba language for participants with LBP. The ODI was translated into Yoruba, and this translated version was analysed in terms of semantics and linguistics. Then, the Yoruba version was translated back into English and both versions administered to 160 participants with LBP. The internal consistency using Cronbach's alpha coefficient, criterion validity and test-retest reliability were assessed using Spearman's rank correlation with significance set at P< 0.05. The inter-rater reliability was evaluated by two different observers and the intra-rater reliability was determined by the same observer, a week apart. The internal consistency of the Yoruba ODI with Cronbach's alpha was 0.97, the intrarater reliability yielded an intraclass correlation coefficient of 0.93 and criterion validity assessed using Spearman's rank correlation was r = 0.92 for highest score and 0.63 for lowest score. The Yoruba ODI is a reliable and valid tool for assessing functional disability in LBP patients.


Molecular characterization of Yersinia enterocolitica strains to evaluate virulence associated genes.
Yersinia enterocolitica (Ye) species is divided into 6 biotypes (BT), 1A, 1B, 2, 3, 4, 5 classified based on biochemical reactions and about 70 serotypes, classified based on the structure of the lipopolysaccharide O-antigen. The BT1A is considered non-pathogenic, while the BT 1B-5 are considered pathogenic. Evaluate the distribution of eleven chromosomal and plasmid virulence genes, ail, ystA, ystB, myfA, hreP, fes, fepD, ymoA, sat, virF and yadA, in 87 Ye strains isolated from food, animals and humans, using two SYBR Green real-time PCR platforms. The main results showed the presence of the ail and ystA genes in all the pathogenic bioserotypes analyzed. The ystB, on the other hand, was identified in all non-pathogenic strains biotype 1A. The target fes, fepD, sat and hreP were found in both pathogenic biotypes and in BT1A strains. The myfA gene was found in all pathogenic biotype and in some Ye BT1A strains. The virF and yadA plasmid genes were mainly detected in bioserotype 4/O:3 and 2/O:9, while ymoA was identified in all strains. The two molecular platforms could be used to better define some specific molecular targets for the characterization and rapid detection of Ye in different sources which important implications for food safety and animal and human health.


Uptake of HIV testing and counseling among tertiary institution students in the Hohoe Municipality, Ghana.
HIV Testing and Counselling (HTC) is a critical strategy to reduce the rate of new HIV infections and the key entry point to HIV treatment, care and support services. This study aimed to determine the uptake of HTC among students of tertiary institutions in the Hohoe Municipality of Ghana. This was a quantitative cross-sectional study. A structured questionnaire was used to collect data among a proportionate stratified sample of students from tertiary institutions. Chi-square and Logistic regression analyses were performed using Stata version 12.0 at the 0.05 level of significance. Only 30.6% of the total respondents had ever tested for HIV/AIDS of which, only 22.9% tested less than 6 months before the current study. Students above twenty-four years of age were 3 times more likely to go for HTC than those below 20 years [OR=2.56 (95% CI: 1.07-6.11; p=0.034)]; those in the fourth year of study were 3 times more likely get HTC than those in the first year [OR=3.05 (95%CI: 1.10-8.49; p=0.033)]; and those attending THERESCO, the Midwifery training college and UHAS were more than 2 times more likely to get tested for HIV than those attending FRANCO [OR =2.67 (95% CI: 1.14-6.15; p=0.024)], [OR=2.40 (95% CI: 1.04-5.54; p=0.040)] and [OR=2.63 (95% CI: 1.13-6.13; p=0.026)] respectively. The uptake of HTC among tertiary institution students in Hohoe municipality was considerably low. Policymakers should design programs and interventions that would increase uptake of HTC among tertiary students, with focus on those aged less than 20 years, those at the lower level of study and those in the non-health related institutions.


Progression of liver fibrosis in patients with chronic hepatitis C after orthotopic liver transplantation.
Hepatitis C virus (HCV)-related cirrhosis is the leading indication for orthotopic liver transplantation (OLTx). HCV recurrence is universal after OLTx, with a highly variable course. This study aimed to find factors that affect progression of fibrosis in recurrent HCV. Fifty-eight HCV patients underwent OLTx at our center who were selected on the basis of available preOLTx serum or explanted liver sample and liver biopsy obtained at least 6 months postOLTx. All liver biopsies were performed when clinically indicated and were scored using the modified Hepatitis Activity Index (HAI). Primary immunosuppression consisted of tacrolimus and prednisone. The group included 41 males (mean age 49.6 years). HCV genotype distribution was 1a, 31 (53%); 1b, 16 (28%), and others 11 (19%). The mean follow-up was 53.1 months. Patients with genotype 1a (n=31; mean 46.3 months) had significantly lower fibrosis-free survival analyzed by the presence of fibrosis stages 5 and 6 when compared with other genotypes (n=27; mean 60.1 months; P=0.0088, log rank test). Mean HAI scores were significantly higher in HCV genotype 1a, although there were no differences in survival between genotypes. Similarly, patients with cytomegalovirus (CMV) infection postOLTx (n=4) had a higher fibrosis progression rate compared with those without CMV (n=54) (mean fibrosis-free survival 29.0 vs. 53.0 months P=0.0004, log-rank test). Human leukocyte antigen matching and rate of acute rejection did not influence progression of fibrosis. Patients with HCV genotype 1a and those developing CMV postOLTx have a higher rate of hepatic fibrosis progression after OLTx for HCV-related chronic liver disease.


Developmental Profile of Psychiatric Risk Associated With Voltage-Gated Cation Channel Activity.
Recent breakthroughs in psychiatric genetics have implicated biological pathways onto which genetic risk for psychiatric disorders converges. However, these studies do not reveal the developmental time point(s) at which these pathways are relevant. We aimed to determine the relationship between psychiatric risk and developmental gene expression relating to discrete biological pathways. We used postmortem RNA sequencing data (BrainSeq and BrainSpan) from brain tissue at multiple prenatal and postnatal time points, with summary statistics from recent genome-wide association studies of schizophrenia, bipolar disorder, and major depressive disorder. We prioritized gene sets for overall enrichment of association with each disorder and then tested the relationship between the association of their constituent genes with their relative expression at each developmental stage. We observed relationships between the expression of genes involved in voltage-gated cation channel activity during early midfetal, adolescence, and early adulthood time points and association with schizophrenia and bipolar disorder, such that genes more strongly associated with these disorders had relatively low expression during early midfetal development and higher expression during adolescence and early adulthood. The relationship with schizophrenia was strongest for the subset of genes related to calcium channel activity, while for bipolar disorder, the relationship was distributed between calcium and potassium channel activity genes. Our results indicate periods during development when biological pathways related to the activity of calcium and potassium channels may be most vulnerable to the effects of genetic variants conferring risk for psychiatric disorders. Furthermore, they indicate key time points and potential targets for disorder-specific therapeutic interventions.


[Role of the bone mineral density investigation through measuring of peripheral dual-energetic x-ray absorption in prevention of fractures in children with osteogenesis imperfecta].
The Osteogenesis imperfecta is hereditary disturbance of collagen biosynthesis. Illness is characterized by frequent fractures that consequently cause functional disturbance of locomotor system as well as deformation of long tubular bones. The distinguishing feature of this illness is the secondary osteoporosis. The latter in its turn worsens clinical course and the outcome of the illness. The purpose of the present work was the study of bone mineral density in children with osteogenesis imperfecta through application of dual energetic x-ray absorption measurements. In total 32 patients 1-15 years of age with osteogenesis imperfecta have been investigated. The patients have been divided into three age groups. Measurement of distal and proximal sections of radius and elbow (ulna) bones was carried out using peripheral dual-energetic x-ray absorption measurements in order to determine the bone mineral density. Results of the bone mineral density (BMD) measurements have proved that children with osteogenesis imperfecta have lower indices in comparison with children of the corresponding age group and has been registered as 3,76 times lower for 1-7 years old children; 2,3 times lower for 7-12 years old children and 1,89 times lower for children 13-15 years of age. Having studied the correlation between downgraded bone mineral density and number of fracture cases, it was registered that the lower is BMD of cortical layer, the higher is the number of fracture cases. Investigating the bone mineral density in children with osteogenesis imperfecta provides opportunity to reveal potential high risk patients with predisposition to the development of fractures and to provide corresponding treatment and preventive measures in these patients.


Identification of asthma-associated microRNAs in bronchial biopsies.
Changes in microRNA (miRNA) expression can contribute to the pathogenesis of many diseases, including asthma. We aimed to identify miRNAs that are differentially expressed between asthma patients and healthy controls, and explore their association with clinical and inflammatory parameters of asthma. Differentially expressed miRNAs were determined by small RNA sequencing on bronchial biopsies of 79 asthma patients and 82 healthy controls using linear regression models. Differentially expressed miRNAs were associated with clinical and inflammatory asthma features. Potential miRNA-mRNA interactions were analysed using mRNA data available from the same bronchial biopsies, and enrichment of pathways was identified with Enrichr and g:Profiler. In total, 78 differentially expressed miRNAs were identified in bronchial biopsies of asthma patients compared with controls, of which 60 remained differentially expressed after controlling for smoking and inhaled corticosteroid treatment. We identified several asthma-associated miRNAs, including miR-125b-5p and miR-223-3p, based on a significant association with multiple clinical and inflammatory asthma features and their negative correlation with genes associated with the presence of asthma. The most enriched biological pathway(s) affected by miR-125b-5p and miR-223-3p were inflammatory response and cilium assembly/organisation. Of interest, we identified that lower expression of miR-26a-5p was linked to more severe eosinophilic inflammation as measured in blood, sputum as well as bronchial biopsies. Collectively, we identified miR-125b-5p, miR-223-3p and miR-26a-5p as potential regulators that could contribute to the pathogenesis of asthma.


ras and myc analysis in primary and metastatic colorectal carcinomas.
Paired primary colorectal adenocarcinoma and normal frozen tissue samples from 60 patients were prospectively studied to determine the frequency of point mutations in K-ras and the occurrence of structural alterations in c-myc. Parallel investigations were performed on liver metastatic specimens from 16 of the patients. 47% of the primary tumors presented point mutations in K-ras; 71% of these were in codon 12. Significant associations were found between codon 13 ras mutations and Dukes' D stage (p<0.05), and between mutations in codon 12 and mucinous type (p<0.01). The c-myc gene structure was altered in 5/60 cases (8%). In 4/16 cases, the K-ras gene status in the primary carcinoma and in the metastatic tissue from the same patient was found to be different. Our results suggest that codon 13 I-as mutations may be associated with an increased invasive and metastatic potential, while codon 12 mutations may have a role in the mucinous differentiation pathway.


Constructing a nomogram based on the distribution of thyroid nodules and suspicious lateral cervical lymph nodes in fine-needle aspiration biopsies to predict metastasis in papillary thyroid carcinoma.
Elevated concentrations of thyroglobulin eluent is a risk factor for lateral cervical lymph node metastasis (LLNM) in patients with papillary thyroid cancer (PTC). We aimed to develop a practical nomogram based on the distribution of thyroid nodules and the presence of suspicious lateral cervical lymph nodes in fine-needle aspiration biopsies (LN-FNABs), including the cytopathology and the suspicious lateral cervical lymph node (LLN) thyroglobulin eluent (Tg), to predict the possibility of LLNM preoperatively in patients with PTC. The clinical data of PTC patients who were admitted to the Third Affiliated Hospital of Soochow University from January 2022 to May 2023 to undergo fine-needle aspiration biopsy (FNAB) were included in this study. A total of 208 patients in 2022 served as the training set (70%), and 89 patients in 2023 served as the validation set (30%). The clinical characteristics and LN-FNAB results were collected to determine the risk factors of LLNM. A preoperative nomogram was developed for predicting LLNM based on the results of the univariate and multivariate analyses. Internal calibration, external calibration, and decision curve analysis (DCA) were performed for these models. The multivariate logistic regression analysis showed that the maximum thyroid nodule diameter (Odds Ratio (OR) 2.323, 95% CI 1.383 to 3.904; p = 0.001), Tg level (OR 1.007, 95% CI 1.005 to 1.009; p = 0.000), Tg divided by serum thyroglobulin, (Tg/sTg) [odds ratio (OR) 1.005, 95% CI 1.001 to 1.008; p = 0.009], and cytopathology (OR 9.738, 95% CI 3.678 to 25.783; p = 0.000) (all p < 0.05) had a significant impact on the LLNM of patients with suspicious LLNs. The nomogram showed a better predictive value in both the training cohort [area under the curve, (AUC) 0.937, 95% CI 0.895 to 0.966] and the validation cohort (AUC 0.957, 95% CI 0.892 to 0.989). The nomogram also showed excellent internal and external calibration in predicting LLNM. According to the DCA, the diagnostic performance of this model was dependent on the following variables: maximum thyroid nodule diameter, Tg level, Tg/sTg, and cytopathology. Based on the aforementioned risk factors, we believe that it is necessary to establish a personalized LLNM model for patients with PTC. Using this practical nomogram, which combines clinical and Tg risk factors, surgeons could accurately predict the possibility of LLNM preoperatively. The nomogram will also help surgeons to establish personalized treatment plans before surgery.


Short communication: Hypernatremia in diarrheic calves associated with oral electrolyte administration in water and milk replacer in absence of access to water.
A major goal in treatment of calves with diarrhea is to restore hydration and to correct metabolic acidosis. This can be achieved by the administration of oral electrolyte solutions (OES). However, the composition of OES products and the administration protocols in practice vary widely, which can potentially compromise the efficacy and safety of these treatments. In particular, administration of OES in milk replacer (MR) and the absence of water supply in young calves are not unusual and these conditions could compromise calf health. In this light, the objective of this study was to evaluate the efficacy and safety of OES administered in MR and in water without access to water. Forty-five male Holstein calves (16.6 ± 1.6 d of age and 45.4 ± 2.2 kg at arrival) were purchased from a collection center located in the Netherlands. After arrival, calves went through an adaptation period of 4 d. Calves that developed diarrhea within 6 d after the end of the adaptation period were enrolled in the study, and the remaining calves were sold after being weaned. Upon morning detection of abnormal fecal scores (d 1 starting point), calves were blocked based on initial BW. Within each block, calves were randomly assigned to 1 of 2 treatments, including a control consisting of a small dose of whey (CON; n = 12) and an OES treatment (OES; n = 14). Treatments were blinded to the farm staff by randomly assigning a letter to each treatment. Treatments were simultaneously administered for 4 d in MR (2.5 L at 0800 and 1730 h) and in water (3 L at 1300 and 2200 h). Calves had no supplemental access to plain water. Blood samples were taken at 0600 h for 4 d, and fecal scores (0 = normal; 1 = watery feces) were assessed daily at 0900 h for 15 consecutive days. Additionally, skin turgor and degree of enophthalmos were assessed at 1000 h from d 1 to 4 using a 3-level scoring system. Calves fed OES had a higher prevalence of diarrhea on d 3, 4, and 5 as well as higher prevalence of delayed skin turgor and increased degree of enophthalmos over the 4 monitoring days. Diarrhea duration was longer in calves receiving OES than in calves receiving CON (4.2 d vs. 2.1 d, respectively). The OES treatment resulted in hypernatremia (serum Na+ >145 mmol/L) within 48 h after the first OES administration. Hypernatremia was linked with higher serum Cl- and urea concentrations and thus higher serum osmolarity in OES calves compared with CON calves. Administered under these conditions, OES resulted in various degrees of hypernatremia and a delayed recovery from diarrhea, thus defeating the purpose of OES administration.


Synthesis and biological evaluation against H. pylori of chitosan menthone Schiff base hybrid with different types of inorganic nanoparticles.
The production of novel natural medicines for the treatment of Helicobacter pylori (H. pylori) has lately attracted a lot of interest. Some bacterial infections have traditionally been alleviated by terpenes. The present work intended to examine the impact of several chitosan menthone Schiff base nanocomposites on the treatment of H. pylori infection as well as on its Anti-inflammatory capacity. Chitosan (Cs) was condensed with menthone with different molar ratios of Cs:menthone (1,0.5, 1:1, and 1:2) to produce chitosan Schiff bases namely; Cs-SB1, Cs-SB2, and Cs-SB3, respectively. Cs-SB3 Schiff base nanocomposites were prepared individually by adding 2%Ag, 2%Se, (1%Ag + 1%Se), and 2%Fe2O3 nanoparticles to produce compounds denoted as Cs-SB-Ag, Cs-SB-Se, Cs-SB-Ag/ Se, and Cs-SB-Fe, respectively. The anti-H. pylori activity of Cs-SB-Se was detected at a minimal inhibitory concentration MIC of 1.9 μg/mL making it the most biologically active compound in our study. Cs-SB-Se nanocomposite was tested for its cyclooxygenases (COX-1 and COX-2) inhibitory potential which demonstrated inhibitory efficacy towards COX enzymes with inhibition value against COX-1 (IC50 = 49.86 ± 1.784 μg/mL) and COX-2(IC50 = 12.64 ± 0.463 μg/mL) which were less than the well-known Celecoxib (22.65 ± 0.081 and 0.789 ± 0.029 μg/mL) and Indomethacin (0.035 ± 0.001 and 0.08 ± 0.003 μg/mL) inhibitors. The selectivity index SI = 3.94 for tested nanocomposites indicated higher selectivity for COX-1. The cytotoxicity of the Cs-SB-Se nanocomposite was evaluated in Vero cells (CCL-81) and it showed that at a concentration of 62.5 μg/mL, cell viability was 85.43 %.


The use of aromatherapy in intrapartum midwifery practice an observational study.
The authors report the process and results of an evaluation of a midwifery aromatherapy service for mothers in labour: This study of 8058 mothers in childbirth, is the largest research initiative in the use of aromatherapy within a health-care setting. The study involved a wide range of participants, from mothers who experienced a low risk, spontaneous labour and birth, to those whose labour was induced, and those who had vaginal operative delivery and Caesarean section. The study-took place over a period of 8 years, which enabled a more challenging test of the effect of aromatherapy on intrapartum midwifery practice and outcomes. In the study a total of 10 essential oils were used, plus a carrier oil, which were administered to the participants via skin absorption and inhalation. The study found little direct evidence that the practice of aromatherapy per se reduces the need for pain relief during labour, or the incidence of operative delivery. But a key finding of this study suggests that two essential oils, clary sage and chamomile are effective in alleviating pain. The evidence from this study suggests that aromatherapy can be effective in reducing maternal anxiety, fear and/or pain during labour. The use of aromatherapy appeared to facilitate a further reduction in the use of systemic opioids in the study centre, from 6% in 1990 to 0.4% in 1997 (per woman). Aromatherapy is an inexpensive care option. In 1997 when 1592 mothers used aromatherapy, the total cost was 769.17 Pounds. The study reports a minimal incidence of associated symptoms. Out of 8058 mothers, 1% (100) recorded an associated symptom. These were mild in nature. The successful model of integrated practice that this aromatherapy study presents, offers a useful example for other units to consider.


Adsorption and removal of polystyrene nanoplastics from water by green-engineered clays.
Human exposure to micro- and nanoplastics (MNPs) commonly occurs through the consumption of contaminated drinking water. Among these, polystyrene (PS) is well-characterized and is one of the most abundant MNPs, accounting for 10 % of total plastics. Previous studies have focused on carbonaceous materials to remove MNPs by filtration, but most of the work has involved microplastics since nanoplastics (NPs) are smaller in size and more difficult to measure and remove. To address this need, green-engineered chlorophyll-amended sodium and calcium montmorillonites (SMCH and CMCH) were tested for their ability to bind and detoxify parent and fluorescently labeled PSNP using in vitro, in silico, and in vivo assays. In vitro dosimetry, isothermal analyses, thermodynamics, and adsorption/desorption kinetic models demonstrated 1) high binding capacities (173-190 g/kg), 2) high affinities (103), and 3) chemisorption as suggested by low desorption (≤42 %) and high Gibbs free energy and enthalpy (>|-20| kJ/mol) in the Langmuir and pseudo-second-order models. Computational dynamics simulations for 30 and 40 monomeric units of PSNP depicted that chlorophyll amendments increased the binding percentage and contributed to the sustained binding. Also, 64 % of PSNP bind to both the head and tail of chlorophyll aggregates, rather than the head or tail only. Fluorescent PSNP at 100 nm and 30 nm that were exposed to Hydra vulgaris showed concentration-dependent toxicity at 20-100 µg/mL. Importantly, the inclusion of 0.05-0.3 % CMCH and SMCH significantly (p ≤ 0.01) and dose-dependently reduced PSNP toxicity in morphological changes and feeding rate. The bioassay validated the in vitro and in silico predictions about adsorption efficacy and mechanisms and suggested that CMCH and SMCH are efficacious binders for PSNP in water.


Cognitive spectroscopy for wood species identification: near infrared hyperspectral imaging combined with convolutional neural networks.
From the viewpoint of combating illegal logging and examining wood properties, there is a contemporary demand for a wood species identification system. Several nondestructive automatic identification systems have been developed, but there is room for improvement to construct a highly reliable model. The present study proposes cognitive spectroscopy that combines near infrared hyperspectral imaging (NIR-HSI) with a deep convolutional neural network approach. We defined "cognitive spectroscopy" as a protocol that extracts features from complex spectroscopic data and presents the best results without human intervention. Overall, 120 samples representing 38 hardwood species were scanned using an NIR-HSI camera. A deep learning prediction model was built based on the principal component (PC) images obtained from the PC scores of hyperspectral images (wavelength range: 1000-2200 nm at approximately 6.2 nm interval). The results showed that the accuracy of wood species identification based on 6PC (PC1-PC6) images was 90.5%, which was considerably higher than the accuracy of 56.0% obtained with conventional visible images.


Fiber tracking at term displays gender differences regarding cognitive and motor outcome at 2 years of age in preterm infants.
White matter microstructural changes can be detected with diffusion tensor imaging. It was hypothesized that diffusion parameters in the posterior limb of the internal capsule (PLIC) and corpus callosum (CC) bundles in preterm infants at term equivalent age (TEA) were associated with neurodevelopment at 2 y corrected age. In 67 preterm infants, fiber tracking was performed at TEA for the CC and both PLIC bundles. Volume, length, fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity were determined for the three bundles. These parameters were assessed in relation to outcome on the Bayley Scales of Infant and Toddler Development III. In girls, volume and length of the CC bundle and right PLIC bundle volume were associated with cognition. In boys, volume, FA, mean and radial diffusivity, and length of the left PLIC were associated with fine motor scores. Correction for GA, birth weight, intraventricular hemorrhage, white matter injury, and maternal education did not change the results. Fiber tracking parameters in the PLIC and CC bundles in preterm infants at TEA revealed different associations with neurodevelopment between boys and girls. This study suggested that fiber tracking is a useful method to predict neurodevelopment in preterm infants.


Are thiosulfate and trithionate intermediates in dissimilatory sulfate reduction?
The fate of 35-S during anaerobic metabolism of [35-S]sulfate, [35-S]thiosulfate, and [35-S]sulfate plus unlabeled thiosulfate by washed cell suspensions of Desulfovibrio spp, and of [35-S]thiosulfate by growing D. desulfuricans was examined. The results appear to be inconsistent with the hypothesis that thiosulfate is an intermediate in sulfate reduction. Since thiosulfate was produced from trithionate, the latter is also unlikely to be an intermediate in the reduction pathway. Extracts of D. desulfuricans catalysed exchange between sulfite and the sulfonate group of thiosulfate.


PICOT (GLRX3) is a positive regulator of stress-induced DNA-damage response.
Protein kinase C (PKC)-interacting cousin of thioredoxin (PICOT; also termed glutaredoxin 3 (Glrx3)) is a ubiquitously expressed protein that possesses an N-terminal monothiol thioredoxin (Trx) domain and two C-terminal tandem copies of a monothiol Glrx domain. It has an overall highly conserved amino acid sequence and is encoded by a unique gene, both in humans and mice, without having other functional gene homologs in the entire genome. Despite being discovered almost two decades ago, the biological function of PICOT remains largely ill-defined and its ramifications are underestimated considering the fact that PICOT-deficiency in mice results in embryonic lethality. Since classical Glrxs are important regulators of the cellular redox homeostasis, we tested whether PICOT participate in the stress-induced DNA-damage response, focusing on nuclear proteins that function as integral components of the DNA repair machinery. Using wild type versus PICOT-deficient (PICOT-KD) Jurkat T cells we found that the anti-oxidant mechanism in PICOT-deficient cells is impaired, and that these cells respond to genotoxic drugs, such as etoposide and camptothecin, by increased caspase-3 activity, a reduced survival and a slower and diminished phosphorylation of the histone protein, H2AX. Nevertheless, the effect of PICOT on the drug-induced phosphorylation of H2AX was independent of the cellular levels of reactive oxygen species. PICOT-deficient cells also demonstrated reduced and slower γH2AX foci formation in response to radiation. Furthermore, immunofluorescence staining using PICOT- and γH2AX-specific Abs followed by confocal microscopy demonstrated partial localization of PICOT at the γH2AX-containing foci at the site of the DNA double strand breaks. In addition, PICOT knockdown resulted in inhibition of phosphorylation of ATR, Chk1 and Chk2 kinases, which play an essential role in the DNA-damage response and serve as upstream regulators of γH2AX. The present data suggest that PICOT protects cells from DNA damage-inducing agents by operating as an upstream positive regulator of ATR-dependent signaling pathways. By promoting the activity of ATR, PICOT indirectly regulates the phosphorylation and activation of Chk1, Chk2, and γH2AX, which are critical components of the DNA damage repair mechanism and thereby attenuate the stress- and replication-induced genome instability.


Influence of body composition, muscle strength, diet and physical activity on total body and forearm bone mass in Chinese adolescent girls.
The aim of the present study was to determine association between body composition, muscle strength, diet and physical exercise with bone mineral content (BMC) and bone area (BA) in 283 Chinese adolescent girls aged 15 years in Beijing, China. Body composition, pubertal stage, physical activity and dietary intakes were assessed using standard validated protocols. Total body and forearm bone, lean body mass (LBM) and fat body mass (FBM) were determined by dual X-ray absorptiometry. Multivariate linear regression analyses were carried out to examine the predictors of BMC and BA, after controlling for potential confounders. The subjects had a mean age of 15.0 (sd 0.9) years and 99.6 % of them had reached menarche. Multivariate analyses showed that LBM, FBM, handgrip muscle strength and milk intake were significant independent determinants of BMC and BA of the total body and/or forearm sites. LBM was found to be a stronger independent determinant than FBM of BMC and BA, whereas handgrip muscle strength was only found as significant determinant of BMC and BA at the forearm sites than in total body BMC and BA. Further, total physical activity level had a significant positive association with handgrip and LBM. This suggested that greater muscle strength and higher LBM may reflect higher levels of physical activity. Therefore, continuous healthy lifestyle practices such as adequate intake of milk and continuous participation in physical activity should be encouraged throughout adolescence to optimise bone growth during this period.


The impact of EGFR mutations on the incidence and survival of stages I to III NSCLC patients with subsequent brain metastasis.
Previous studies have demonstrated the association between EGFR mutations and distant metastasis. However, the association for subsequent brain metastasis (BM) in stages I-III non-small cell lung cancer (NSCLC) patients remains inconclusive. We conducted a retrospective analysis to clarify the impact of EGFR mutations on the incidence of BM and associated survival in patients with stage I-III NSCLC. A total of 491 patients screened for EGFR mutations were retrospectively enrolled. Brain MRI or CT was used to detect the BM. Cumulative incidence of subsequent BM and overall survival (OS) after diagnosis of BM were estimated by the Kaplan-Meier method and compared using log-rank test. We performed Cox proportional hazard regression for predictors of subsequent BM and determinants of OS after BM. The cumulative incidence of BM seemed higher in patients harboring EGFR mutations than those without EGFR mutations although it did not reach statistical significance (hazard ratio [HR] = 1.75, 95% confidence interval [CI] = 0.73~1.81). After adjusting possible confounders, including age, smoking, stage, and tumor size, EGFR mutation became one of the predictors for subsequent BM (HR = 1.89, 95% CI = 1.12~3.17, p = 0.017). Though there was no statistical difference in survival after BM between patients with EGFR mutations and wild-type EGFR (median survival: 17.8 vs. 12.2 months, HR = 0.79, 95% CI = 0.45-1.40), patients with EGFR 19 deletion (Del) tended to have a longer survival after BM than the non-EGFR 19 Del group (median survival: 29.4 vs. 14.3 months, HR 0.58, 95% CI = 0.32-1.09, p = 0.089). In conclusion, our data suggested EGFR mutation to be one of the predictors for subsequent BM in stage I-III patients. Given the small sample size, more studies are warranted to corroborate our results.


Landscape diversity and local temperature, but not climate, affect arthropod predation among habitat types.
Arthropod predators are important for ecosystem functioning by providing top-down regulation of insect herbivores. As predator communities and activity are influenced by biotic and abiotic factors on different spatial scales, the strength of top-down regulation ('arthropod predation') is also likely to vary. Understanding the combined effects of potential drivers on arthropod predation is urgently needed with regard to anthropogenic climate and land-use change. In a large-scale study, we recorded arthropod predation rates using artificial caterpillars on 113 plots of open herbaceous vegetation embedded in contrasting habitat types (forest, grassland, arable field, settlement) along climate and land-use gradients in Bavaria, Germany. As potential drivers we included habitat characteristics (habitat type, plant species richness, local mean temperature and mean relative humidity during artificial caterpillar exposure), landscape diversity (0.5-3.0-km, six scales), climate (multi-annual mean temperature, 'MAT') and interactive effects of habitat type with other drivers. We observed no substantial differences in arthropod predation rates between the studied habitat types, related to plant species richness and across the Bavarian-wide climatic gradient, but predation was limited when local mean temperatures were low and tended to decrease towards higher relative humidity. Arthropod predation rates increased towards more diverse landscapes at a 2-km scale. Interactive effects of habitat type with local weather conditions, plant species richness, landscape diversity and MAT were not observed. We conclude that landscape diversity favours high arthropod predation rates in open herbaceous vegetation independent of the dominant habitat in the vicinity. This finding may be harnessed to improve top-down control of herbivores, e.g. agricultural pests, but further research is needed for more specific recommendations on landscape management. The absence of MAT effects suggests that high predation rates may occur independent of moderate increases of MAT in the near future.


The generation and resemblance heuristics in face recognition: cooperation and competition.
Like all probabilistic decisions, recognition memory judgments are based on inferences about the strength and quality of stimulus familiarity. In recent articles, B. W. A. Whittlesea and J. Leboe (2000; J. Leboe & B. W. A. Whittlesea, 2002) proposed that such memory decisions entail various heuristics, similar to well-known heuristics in overt decision making. Using verbal stimulus materials, Whittlesea and Leboe illustrated 3 separate memory heuristics: fluency, generation, and resemblance. In the present investigation, the authors examined the generation and resemblance heuristics in face recognition. In 12 experiments, people memorized faces and later performed exclusion (source memory) tasks. Every experiment contained natural groups of facial photographs (e.g., Caucasian vs. Asian faces), but such groups were not always valid source-memory predictors. Instead, across experiments, the potential utility of generation and resemblance strategies was systematically varied. People were quite sensitive to such variations, changing from one heuristic to another as needed. However, they also combined heuristics, both improving and damaging performance across conditions. The relevance of recognition decision heuristics to eyewitness memory is considered.


Caffeic acid phenethyl ester modulates gentamicin-induced oxidative nephrotoxicity in kidney of rats.
In this study, the modulator effect of caffeic acid phenethyl ester (CAPE) on the oxidative nephrotoxicity of gentamicin in the kidneys of rats was investigated by determining indices of lipid peroxidation and the activities of antioxidant enzymes as well as by histological analyses. Forty female Wistar albino rats were randomly divided into four groups, namely control, gentamicin, CAPE, and gentamicin plus CAPE. On the 12th day of the study, all rats were sacrificed and then blood samples and kidneys were taken. Lipid peroxidation and nitric oxide levels, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) enzyme activities, and histological evaluation were measured in kidneys of rats. Levels of blood urea nitrogen and creatinine were studied in serum. CAPE with gentamicin caused decreases in lipid peroxidation, nitric oxide, urea nitrogen, and creatinine levels, although it caused increases in CAT, GSH-Px, and SOD activities when compared with gentamicin alone. In addition, on histological evaluation, the renal damage caused by gentamicin alone appeared much higher than that caused by CAPE plus gentamicin. It is concluded that oxidative stress plays a critical role in causing gentamicin nephrotoxicity and that this nephrotoxicity may be significantly reduced by CAPE.


Positive tuberculin skin tests and isoniazid chemoprophylaxis.
The American Thoracic Society recommends that specific individuals who are classified as tuberculosis infected receive a year-long course of INH chemoprophylaxis. They further recommend that patients receiving medication be evaluated on a monthly basis to assess the individual for side effects related to the medication. The most prevalent side effects are hypersensitivity, GI distress, hepatitis and neurotoxicity. Subjective data relating to these side effects need to be elicited at every visit and a pertinent physical examination done. Careful monthly monitoring is required to evaluate the patient for the most prevalent and significant side effects of the medication. Nurses must be aware of the significance of this preventive measure, the adverse reactions which may occur with the drug therapy and the health teaching which contributes to patient compliance.


Effect of incorporating flat aromatic molecules on spherical polymeric nanoparticles.
Flat aromatic structures are ubiquitous in organic semiconducting molecules. The possibility of endowing these inherently anisotropic molecules with isotropic structures is explored using a polymeric nanoparticle attachment strategy. Preliminary findings, outlined in this manuscript, suggest that this might be a simple and effective strategy for organic semiconductors with consistent mobilities.


The distribution of subarctic and boreal deep-sea demersal fish assemblages across environmental gradients of the northwest Atlantic.
The oceanography of the Labrador Sea is well studied because of its globally important deep-water convection that oxygenates the deep ocean and drives climate-regulating ocean currents. However, little is known about the fish communities that inhabit this area, particularly beyond the depths accessible to standard research surveys and commercial fishing activities. We used baited longline surveys to characterize important components of demersal fish communities across a depth gradient of 200-3000 m and compared these data to a similar dataset collected c. 1200 km to the south in the Flemish Cap Region. We found demersal fish communities in the Labrador Sea to be similar to those of the Flemish Cap Region despite unique oceanography and lower primary productivity in the Labrador Sea. Moreover, both areas had high abundance, biomass, and species richness at intermediate depths that suggests factors beyond depth drive community structure in the deep ocean. These data are important for identifying high-value areas for potential protective measures in the northwest Atlantic and provide necessary data with which to assess potential environmental impacts of extractive industries that are expanding north and to deeper waters.


Is the obstetric guideline of 30 minutes from decision to incision for Cesarean delivery clinically significant?
A Cesarean delivery may be critical to the health and wellbeing of a newborn. The time required to extract an infant from a hostile in utero environment is a frequent issue in medical negligence cases. The American College of Obstetricians and Gynecologists and the American Academy of Pediatrics suggest a time guideline of 30 minutes from decision for Cesarean delivery to the beginning (incision) of the procedure. This time frame is based on survey data from hospitals throughout the United States and is not based on clinical outcomes or the pathophysiology of obstetric events. This review focuses on specific Cesarean indications as noted by the specialty groups and analyzes them from an outcome point of view. The authors conclude that specific high-risk factors do indeed warrant delivery in as expedient a fashion as possible; however, compliance with the 30-minute guideline does not necessarily lead to a difference in outcome as far as the neonate is concerned.


Early detection of perinatal human immunodeficiency virus (HIV) type 1 infection using HIV RNA amplification and detection. New York City Perinatal HIV Transmission Collaborative Study.
Early diagnosis of perinatally transmitted human immunodeficiency virus type 1 (HIV) infection can guide early interventions. HIV coculture and DNA polymerase chain reaction (DNA-PCR) detect few HIV-infected infants at birth and 90%-100% by age 3 months. Because extracellular HIV RNA may appear soon after infection, a plasma HIV RNA assay was compared with DNA-PCR for early detection of perinatally infected infants. Blood-draw specimens (108) obtained at the same time from 49 HIV-infected infants and 10 specimens from 8 uninfected infants were tested. HIV RNA and DNA-PCR positivity rates were 56% and 33%, respectively, in 36 specimens from 36 infants <28 days of age (binomial test, P = .001). Among 81 specimens obtained after age 14 days, 79 (98%) were positive by HIV RNA testing. No HIV-infected infant specimens were DNA-PCR-positive and HIV RNA-negative. All specimens from 8 uninfected infants were HIV RNA-negative. These results suggest that plasma HIV RNA was detectable earlier and more reliably than HIV DNA in perinatal infection.


Effects of tibolone and its metabolites on prolactin and insulin-like growth factor binding protein-1 expression in human endometrial stromal cells.
The effects of the postmenopausal replacement steroid tibolone and its 3α-, 3β-OH and Δ-4 tibolone metabolites were evaluated on progesterone receptor-mediated classic decidualization markers insulin-like growth factor binding protein-1 (IGFBP-1) and prolactin expression in human endometrial stromal cells (HESCs). Supernatants of conditioned medium or erxtracted RNA from experimental cell incubations of confluent HESCs were subjected to ELISAs, Western blot analysis and RT/PCR, and results were statisically assesed. Over 21 days, specific ELISAs observed linear increases in secreted IGFBP-1 and prolactin levels elicited by tibolone and its metabolites. Cultured HESCs were refractory to E2 and dexamethasone, whereas tibolone and each metabolite exceeded medroxyprogesterone acetate in significantly elevating IGFBP-1 and prolactin output. Anti-progestins eliminated IGFBP-1 and prolactin induction by tibolone and its metabolites. Immunoblotting and RT/PCR confirmed ELISA results. These observations of IGFBP-1 and prolactin expression: (a) indicate the relevance of cultured HESCs in evaluating the chronic effects of tibolone administration to women; (b) are consistent with PR-mediated endometrial atrophy and protection against endometrial bleeding despite the persistence of circulating ER-binding, but not PR-binding metabolites following tibolone administration to women.


In the darkness of the polar night, scallops keep on a steady rhythm.
Although the prevailing paradigm has held that the polar night is a period of biological quiescence, recent studies have detected noticeable activity levels in marine organisms. In this study, we investigated the circadian rhythm of the scallop Chlamys islandica by continuously recording the animal's behaviour over 3 years in the Arctic (Svalbard). Our results showed that a circadian rhythm persists throughout the polar night and lasts for at least 4 months. Based on observations across three polar nights, we showed that the robustness and synchronicity of the rhythm depends on the angle of the sun below the horizon. The weakest rhythm occurred at the onset of the polar night during the nautical twilight. Surprisingly, the circadian behaviour began to recover during the darkest part of the polar night. Because active rhythms optimize the fitness of an organism, our study brings out that the scallops C. islandica remain active even during the polar night.


[Dietary chloride deficiency in premature infants?].
In recent years uncontrolled decrease of chloride contents in some charges of infant formulas has caused chloride deficiency in some infants. The chloride requirement in infants of 5.8 kg has been estimated to be 3.6 mmol/d. Accordingly, prematures of 1.3 kg would require about 2.6 mmol/d. Considering the daily intake of fluid, the minimum concentration of chloride of a formula for infants has to be 4.5 mmol/l and a formula for prematures 11.8 mmol/l. In 4 formulas for prematures and 7 humanized formulas for infants the concentration of chloride ranged from 7.1 to 15.8 mmol/l. In the FRG some prematures may have an inadequate intake of chloride.


Adverse effects of crystalloid and colloid fluids.
Guidelines for infusion fluid therapy rarely take into account that adverse effects occur in a dose-dependent fashion. Adverse effects of crystalloid fluids are related to their preferential distribution to the interstitium of the subcutis, the gut, and the lungs. The gastrointestinal recovery time is prolonged by 2 days when more than 2 litres is administered. Infusion of 6-7 litres during open abdominal surgery results in poor wound healing, pulmonary oedema, and pneumonia. There is also a risk of fatal postoperative pulmonary oedema that might develop several days after the surgery. Even larger amounts cause organ dysfunction by breaking up the interstitial matrix and allowing the formation of lacunae of fluid in the skin and central organs, such as the heart. Adverse effects of colloid fluids include anaphylactic reactions, which occur in 1 out of 500 infusions. The possibility that hydroxyethyl starch causes kidney injury in patients other than those with sepsis is still unclear. For both crystalloid and colloid fluids, coagulation becomes impaired when the induced haemodilution has reached 40%. Coagulopathy is aggravated by co-existing hypothermia. Although oedema can occur from both crystalloid and colloid fluids, these differ in pathophysiology. To balance fluid-induced adverse effects, this review suggests that a colloid fluid is indicated when the infused crystalloid volume exceeds 3-4 litres, plasma volume support is still needed, and the transfusion of blood products is not yet indicated.


[Involvement of medullary tail-flick related neurons in the descending facilitating effects evoked by stimulation of lateral habenular nucleus].
In lightly anesthetized rats 3 classes of neurons in the rostral ventromedial medulla (RVM) were in relation to tail-flick reflex (TF) recorded, i. e. the TF triggired on-cells, the TF triggered off-cells and the non-responsive or neutral cells. When lateral habenular nucleus (LHb) was stimulated the on-cells were excited, the off-cells inhibited while the neutral cells unaffected. The fact that stimulation of LHb facilitated tail-flick reflex appears to be quite well explained by its enhancement effect on the tail-flick related response of both the on- and the off-cells. These results indicate that the facilitating action of LHb on spinal defensive reflex is probably brought out by participation of the medullary tail-flick related cell activity.


Ultrathin porous PdCu metallenezymes as oxidase mimics for colorimetric analysis.
Ultrathin porous and highly curved two-dimensional PdCu alloy metallene are shown to be highly efficient oxidase mimics. Serving as intrinsic oxidase mimic, the ultrathin porous structure of the PdCu metallenezymes could effectively utilize all the Pd atoms of the metallenezymes during catalytic reactions. By using the oxidation capability of 3,3'5,5'-tetramethylbenzidine as distinctive chromogenic substrate, the PdCu metallenezymes was used as oxidase-like mimics for determination of total antioxidant capacity (TAC) of vitamin C containing real products including fresh orange juice, commercial beverages, Vitamin C tablets and dermo-cosmetic products. AAP was hydrolyzed using ALP to generate AA and the corresponding ALP activity was successfully detected in the 0-100 U/L range with a lowest detection limit of 0.9 U/L. This study demonstrates the significant catalytic performance and oxidase-like activity of PdCu metallene nanozyme providing a strategy to develop a TAC assay for the assessment of antioxidant food quality as well as oxidative stress in skin and health care products.


Enteric fever: a travel medicine oriented view.
Enteric fever continues to be an important infection among populations in endemic countries and among travelers to these areas. This review aims to describe recent epidemiological trends and developments in diagnosis, treatment and prevention. Data indicate that the burden of enteric fever is declining in many middle-income countries, whereas the bulk of cases occur in the Indian subcontinent and in south-east Asia. In these regions, Salmonella Paratyphi A is increasingly seen and sometimes surpasses Salmonella Typhi as the main pathogen. Enteric fever caused by S. Paratyphi A is indistinguishable from that caused by S. Typhi. In addition, drug resistance, including nalidixic acid/quinolone resistance now occurs in the majority of clinical isolates of S. Typhi and S. Paratyphi A in Asia. Currently, third generation cephalosporins and azythromycin are the only reasonable therapeutic options for most cases of travel-related enteric fever. The ongoing emergence of S. Paratyphi A results in partial benefit from current typhoid vaccines in the prevention of enteric fever in travelers. Increasing antimicrobial resistance complicates therapy for travel-related enteric fever. New vaccines, offering protection against both agents of enteric fever, are urgently needed; however, none of the current vaccine candidates is likely to be available for several years.


Nitrogen removal characteristics of novel bacterium Klebsiella sp. TSH15 by assimilatory/dissimilatory nitrate reduction and ammonia assimilation.
A novel strain with heterotrophic nitrification and aerobic denitrification was screened and identified as Klebsiella sp. TSH15 by 16S rRNA. The results demonstrated that the ammonia-N and nitrate-N removal rates were 2.99 mg/L/h and 2.53 mg/L/h under optimal conditions, respectively. The analysis of the whole genome indicated that strain TSH15 contained the key genes involved in assimilatory/dissimilatory nitrate reduction and ammonia assimilation, including nas, nar, nir, nor, glnA, gltB, gdhA, and amt. The relative expression levels of key nitrogen removal genes were further detected by RT-qPCR. The results indicated that the N metabolic pathways of strain TSH15 were the conversion of nitrate or nitrite to ammonia by assimilatory/dissimilatory nitrate reduction (NO3-→NO2-→NH4+) and further conversion of ammonia to glutamate (NH4+-N → Glutamate) by ammonia assimilation. These results indicated that the strain TSH15 had the potential to be applied to practical sewage treatment in the future.


Cloning and sequence analysis of cDNAs encoding mammalian mitochondrial malate dehydrogenase.
A cDNA clone, named ppmMDH-1 and covering a part of the porcine mitochondrial malate dehydrogenase (mMDH; L-malate:NAD+ oxidoreductase, EC 22.214.171.124) mRNA, was isolated from a porcine liver cDNA library with a mixture of 24 oligodeoxyribonucleotides as a probe. The sequences of the probe were deduced from the known sequence of porcine mMDH amino acid residues 288-293. ppmMDH-1 covered the coding region for porcine mMDH amino acid residues 17-314 and the 3' untranslated region. Subsequently, mouse mMDH cDNA clones were isolated from a mouse liver cDNA library with the ppmMDH-1 cDNA as a probe. One of the clones, named pmmMDH-1 and containing a cDNA insert of about 1350 base pairs, was selected for sequence analysis, and the primary structure of the mouse precursor form of mMDH (pre-mMDH) was deduced from its cDNA sequence. The sequenced coding regions for the porcine and mouse mMDH mRNAs showed about 85% homology. When the deduced amino acid sequence of the mouse pre-mMDH was compared with that of the porcine mMDH, they shared a 95% homology, and the mouse pre-mMDH yielded a leader sequence consisting of 24 amino acid residues and a mature mMDH, consisting of 314 amino acid residues. The leader sequence contained three basic amino acid residues, no acidic residues, and no hydrophobic amino acid stretch. The mouse mMDH leader sequence was compared with those of three other rodent mitochondrial matrix proteins.


Efficacy of antibiotic prophylaxis for the prevention of Lyme disease: an updated systematic review and meta-analysis.
The clinical value of antibiotic prophylaxis in preventing Lyme disease remains uncertain, owing to a meta-analysis lacking sufficient power to demonstrate efficacy and a more recent trial showing effectiveness but lacking precision. Our objective was to update our prior meta-analysis on antibiotic prophylaxis for the prevention of Lyme disease, to obtain a more precise estimate of treatment effect. Clinical trials were identified by searching MEDLINE, Embase, the Cochrane Library and trial registries, and by an assessment of the bibliographies of retrieved articles and reviews. Trials were selected if their patients were randomly allocated to a treatment or placebo group within 72 h following an Ixodes tick bite and had no clinical evidence of Lyme disease at enrollment. Details of the trial design, patient characteristics, interventions and outcomes were extracted from each article. Study quality was assessed using the Jadad scale. Four placebo-controlled clinical trials were included for review. Among 1082 randomized subjects, the risk of Lyme disease in the placebo group was 2.2% [95% confidence interval (CI), 1.2%-3.9%] compared with 0.2% (95% CI, 0.0%-1.0%) in the antibiotic-treated group. Antibiotic prophylaxis significantly reduced the odds of developing Lyme disease compared with placebo (pooled odds ratio=0.084; 95% CI, 0.0020-0.57; P=0.0037). The available evidence to date supports the use of antibiotic prophylaxis for the prevention of Lyme disease in endemic areas following an Ixodes tick bite. Pooled data from four placebo-controlled trials suggests that one case of Lyme disease is prevented for about every 50 patients who are treated with antibiotics.


Intratumoral hu14.18-IL-2 (IC) induces local and systemic antitumor effects that involve both activated T and NK cells as well as enhanced IC retention.
hu14.18-IL-2 (IC) is an immunocytokine consisting of human IL-2 linked to hu14.18 mAb, which recognizes the GD2 disialoganglioside. Phase 2 clinical trials of i.v. hu14.18-IL-2 (i.v.-IC) in neuroblastoma and melanoma are underway and have already demonstrated activity in neuroblastoma. We showed previously that intratumoral hu14.18-IL-2 (IT-IC) results in enhanced antitumor activity in mouse models compared with i.v.-IC. The studies presented in this article were designed to determine the mechanisms involved in this enhanced activity and to support the future clinical testing of intratumoral administration of immunocytokines. Improved survival and inhibition of growth of both local and distant tumors were observed in A/J mice bearing s.c. NXS2 neuroblastomas treated with IT-IC compared with those treated with i.v.-IC or control mice. The local and systemic antitumor effects of IT-IC were inhibited by depletion of NK cells or T cells. IT-IC resulted in increased NKG2D receptors on intratumoral NKG2A/C/E⁺ NKp46⁺ NK cells and NKG2A/C/E⁺ CD8⁺ T cells compared with control mice or mice treated with i.v.-IC. NKG2D levels were augmented more in tumor-infiltrating lymphocytes compared with splenocytes, supporting the localized nature of the intratumoral changes induced by IT-IC treatment. Prolonged retention of IC at the tumor site was seen with IT-IC compared with i.v.-IC. Overall, IT-IC resulted in increased numbers of activated T and NK cells within tumors, better IC retention in the tumor, enhanced inhibition of tumor growth, and improved survival compared with i.v.-IC.


Longitudinal examination of cervical volume and vascularization changes during the antepartum and postpartum period using three-dimensional and power Doppler ultrasound.
To assess longitudinally the changes in cervical volume and vascularization during the peripartum period using three-dimensional ultrasound (3D US) and power Doppler and to determine whether these measures change with gestational complications. Longitudinal measurements of cervical dimensions by transvaginal 3D US and power Doppler using the virtual organ computer-aided analysis program were performed at 11-14, 22-24, 32-34 weeks' gestation, and at 6 weeks' postpartum in 111 pregnant women. Comparisons were made between women who delivered at term (vs. preterm), nulliparous (vs. parous), with (vs. without) pre-eclampsia and those with (vs. without) gestational diabetes. After establishing reference values for each peripartum period for cervical volume, vascularization index (VI) and flow index (FI), we found that the 2(nd) and 3(rd) trimester volume, 2(nd) trimester FI and postpartum VI were different in nulli- vs. multiparous women. Volume and vascularization parameters were unaffected by preterm labor. Second trimester VI and vascularization flow index values were lower in pre-eclamptic vs. non-pre-eclamptic women (P<0.05), but unaffected by gestational diabetes. Cervical volume and vascularization parameters are not helpful in predicting preterm labor and gestational diabetes, but might be associated with pre-eclampsia.


Preanalytical phase of sport biochemistry and haematology.
Biochemistry and haematology are more and more important and sometimes crucial in sport medicine for diagnosing, controlling and preventing purposes. The analytical process and the global laboratory quality are heavily influenced by the preanalytical phase, including biological material collection, identification, storage and transport of the specimen, preparation for analyses of the specimen through centrifugation, freezing and thawing, aliquoting and sampling. The increasing interest of sport biochemistry should be linked to a knowledge of principal problems and pitfalls in the preanalytical phase of various parameters, commonly used in following training, diet, and performances of athletes, to avoid misinterpretation of data and to improve usefulness of biochemical investigations. We prepared a practical review of preanalytical aspects of principal analyses applied to the athletes. We include the choice of anticoagulant and its limits for haematological tests, the preparation and manipulation of specimens for hormonological investigation, especially for labile molecules, and for cardiac markers, lactate, cytokines, micronutrients, antioxidant molecules. Preanalytical phase of specimens different from blood are also showed, including urine and saliva, and some aspects of preparation of materials to be analyzed with molecular biology technology are treated. Stability of some analytes, when the parameter is fundamental for the clinical usefulness of the results, is supplied. Preparation of the subjects, however, including the possible influence of physical exercise and biological rhythms on the biochemical and haematological parameters, are not listed.


Older adults receiving home enteral nutrition: enteral regimen, provider involvement, and health care outcomes.
Home enteral nutrition (HEN) is most frequently prescribed for older adults. Medicare reimbursement policy limits in-home nursing visits, and in-home professional nutrition services are restricted to those patients with diabetes or predialysis kidney disease. Most older adults receiving HEN rely on informal (family) caregivers to provide HEN care. The purpose of this study was to apply care process theory to identify and investigate variables related to health care outcomes of HEN in a sample of older adults dependent on informal caregivers. We assessed relationships among patient characteristics, the HEN regimen prescription and adherence, formal provider involvement, and health care outcomes. In-home interviews were conducted with a multiethnic (14 white, 8 Hispanic, 7 African American, 1 Asian) sample of 30 older adults (mean = 68.4 years) during their first 3 months of HEN (mean = 1.83 months). Daily enteral intake averaged 1596 +/- 553 kcal. Gastrointestinal complications, occurring in up to 63.3% of patients, interrupted daily infusions. Further, one-third reported tube clogging or leaking, and one-third had tube displacement. Water intake was half of calculated need and associated with decreased urination (p = .001). Average weight change was -4.35 pounds (p = .001), and 17 patients had body mass indexes (BMIs) <18.5. Women had more complications (p = .004), lower enteral intake (p = .009), and lower BMIs (p = .02). Only 6 patients saw dietitians in follow-up care. Complications and type of feeding tube were associated with unscheduled health care visits and readmissions (p < .05). The efficacy of HEN in older adults (ie, reversal of malnutrition and improvements in health, functionality and quality of life) requires more frequent monitoring, reassessment, and intervention from a highly skilled multidisciplinary team that includes dietitians.


Overnight glucose control with an automated, unified safety system in children and adolescents with type 1 diabetes at diabetes camp.
To determine the safety and efficacy of an automated unified safety system (USS) in providing overnight closed-loop (OCL) control in children and adolescents with type 1 diabetes attending diabetes summer camps. The Diabetes Assistant (DIAS) USS used the Dexcom G4 Platinum glucose sensor (Dexcom) and t:slim insulin pump (Tandem Diabetes Care). An initial inpatient study was completed for 12 participants to evaluate safety. For the main camp study, 20 participants with type 1 diabetes were randomized to either OCL or sensor-augmented therapy (control conditions) per night over the course of a 5- to 6-day diabetes camp. Subjects completed 54 OCL nights and 52 control nights. On an intention-to-treat basis, with glucose data analyzed regardless of system status, the median percent time in range, from 70-150 mg/dL, was 62% (29, 87) for OCL nights versus 55% (25, 80) for sensor-augmented pump therapy (P = 0.233). A per-protocol analysis allowed for assessment of algorithm performance. The median percent time in range, from 70-150 mg/dL, was 73% (50, 89) for OCL nights (n = 41) versus 52% (24, 83) for control conditions (n = 39) (P = 0.037). There was less time spent in the hypoglycemic range <50, <60, and <70 mg/dL during OCL compared with the control period (P = 0.019, P = 0.009, and P = 0.023, respectively). The DIAS USS algorithm is effective in improving time spent in range as well as reducing nocturnal hypoglycemia during the overnight period in children and adolescents with type 1 diabetes in a diabetes camp setting.


Ligands of the peroxisome proliferator-activated receptor-gamma and heart failure.
Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors that are related to retinoid, steroid and thyroid hormone receptors. The PPAR subfamily comprises of three members, PPAR-alpha, PPAR-beta and PPAR-gamma. There is good evidence that ligands of PPAR-gamma, including certain thiazolinediones, reduce myocardial tissue injury and infarct size. The use of PPAR-gamma agonists in the treatment of heart failure is, however, controversial.