A study of disseminated intravascular coagulation with the ethanol gelation test in severely injured patients.
The role of intravascular coagulation in severely injured patients was studied by the ethanol gelation test (EGT). Increased frequency of positive EGT's was observed following trauma, the highest on the fifth posttraumatic day (25 %). A positive test did not correlate with the quantity of blood received and the severity of the trauma. Patients with higher haematocrit, serum protein and platelet values showed a positive test more frequently.


Adult congenital heart disease: a 2008 overview.
During the past decades, health care of patients born with congenital heart disease (CHD) has improved substantially, leading to a growing population of adult survivors. Using the recently published and relevant data on adult CHD (ACHD), we reviewed the most common congenital heart defects and discussed important related issues. Adults with CHD most often require specialized medical or surgical care in a tertiary centre. However, this population also need local follow-up; general practitioners and other specialists therefore have to face the complexity of their disease. AREAS OF CONTROVERSIES: Management of pregnancy, non-cardiac surgery, arrhythmias and endocarditis prophylaxis may be challenging in patients with CHD and should be adapted to their condition. The present article summarizes key clinical information on ACHD for the benefit of physicians who are not specialized in this field. Areas timely for developing research Research efforts and education strategies are greatly needed in order to optimize the care of patients with ACHD.


Advances in inhibition of protein-protein interactions targeting hypoxia-inducible factor-1 for cancer therapy.
Hypoxia is a common characteristic of many types of solid tumors and is associated with tumor propagation, malignant progression, and resistance to anti-cancer therapy. HIF-1 pathway is one of the survival pathways activated in tumor in response to hypoxia. In hypoxic condition, hypoxia-inducible factor-1α (HIF-1α) is stabilized and translocated into nucleus where it forms heterodimer with HIF-1β and regulates the expression of a plethora of genes involved in different processes, such as cell proliferation, differentiation, apoptosis, vascularization/angiogenesis, tumor invasion and metastasis. Recruitment of co-activator p300 or CBP to HIF-1α is critical to the transactivation activity of HIF-1 dimer, therefore, small molecules which can block the dimerization of HIF-1α and HIF-1β or inhibit the interaction between HIF-1α and p300 can function as inhibitors of HIF-1 and have the potential to be developed as novel therapies for the treatment of human cancers. In this review, recent progress of small molecular inhibitors of protein-protein interactions targeting HIF-1 is summarized, the mechanism of functions of these compounds and their potential usage as anti-cancer agents have also been discussed.


Fucoidan from Fucus vesiculosus Fails to Improve Outcomes Following Intracerebral Hemorrhage in Mice.
Intracerebral hemorrhage (ICH) is the most fatal stroke subtype, with no effective therapies. Hematoma expansion and inflammation play major roles in the pathophysiology of ICH, contributing to primary and secondary brain injury, respectively. Fucoidan, a polysaccharide from the brown seaweed Fucus vesiculosus, has been reported to activate a platelet receptor that may function in limiting bleeding, and to exhibit anti-inflammatory effects. As such, the aim of the present study was to examine the effects of fucoidan on hemorrhaging and neurological outcomes after ICH. Male CD-1 mice were subjected to experimental ICH by infusion of bacterial collagenase. Animals were randomly divided into the following groups: sham, ICH + vehicle, ICH + 25 mg/kg fucoidan, ICH + 75 mg/kg fucoidan, and ICH + 100 mg/kg fucoidan. Brain water content, neurobehavioral outcomes, and hemoglobin content were evaluated at 24 h post ICH. Our findings show that fucoidan failed to attenuate the ICH-induced increase in BWC. The neurological deficits that result from ICH also did not differ in the treatment groups at all three doses. Finally, we found that fucoidan had no effect on the hemoglobin content after ICH. We postulate that fucoidan treatment did not improve the measured outcomes after ICH because we used crude fucoidan, which has a high molecular weight, in our study. High-molecular-weight fucoidans are reported to have less therapeutic potential than low molecular weight fucoidans. They have been shown to exhibit anti-coagulant and pro-apoptotic properties, which seem to outweigh their anti-inflammatory and potential procoagulant abilities. We propose that using a low-molecular-weight fucoidan, or fractionating the crude polysaccharide, may be effective in treating ICH. Future studies are needed to confirm this.


The structure and interactions of Ca(2+)-ATPase.
Electron crystallographic studies on membrane crystals of Ca(2+)-ATPase reveal different patterns of ATPase-ATPase interactions depending on enzyme conformation. Physiologically relevant changes in Ca2+ concentration and membrane potential affect these interactions. Ca2+ induced difference FTIR spectra of Ca(2+)-ATPase triggered by photolysis of caged Ca2+ are consistent with changes in secondary structure and carboxylate groups upon Ca2+ binding; the changes are reversed during ATP hydrolysis suggesting that a phosphorylated enzyme form of low Ca2+ affinity is the dominant intermediate during Ca2+ transport. A two-channel model of Ca2+ translocation is proposed involving the membrane-spanning helices M2-M5 and M4, M5, M6 and M8 respectively, with separate but interacting Ca2+ binding sites.


Bilateral multiple primary iridociliary cysts - A rare case report.
Iridociliary cysts are often found in patients as an incidental finding during a routine ophthalmic evaluation and if asymptomatic do not require any treatment per se. However, these are often mistaken as iris melanoma and the patient is managed accordingly causing a great deal of inconvenience to the patient as well as the doctor. A 69 year old male presented to the ophthalmic out-patients department for routine ophthalmic evaluation. On examination, he is best corrected visual acuity was 6/9, N6 in both eyes. Post-mydriasis evaluation showed a Grade II nuclear cataract in both eyes. There was a smooth, pigmented mass with a rounded surface projecting from behind the iris resembling an iris melanoma. On further evaluation, he was found to have multiple ciliary body cysts. Ultrasound biomicroscopy is a valuable technique in diagnosing iridociliary cysts.


Changes in quality of life and disease-related symptoms in patients with polycythemia vera receiving ruxolitinib or standard therapy.
Polycythemia vera (PV)-related symptoms may not be adequately controlled with conventional therapy. This current analysis of the RESPONSE trial evaluated the effects of ruxolitinib compared with standard therapy on quality of life (QoL) and symptoms in patients with PV who were hydroxyurea resistant/intolerant. In the previously reported primary analysis, ruxolitinib achieved the primary composite endpoint of hematocrit control and ≥35% reduction in spleen volume at Week 32. The current analysis evaluated patient-reported outcomes using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), the Pruritus Symptom Impact Scale (PSIS), and the Patient Global Impression of Change (PGIC). Compared with standard therapy, ruxolitinib was associated with greater improvements in global health status/QoL, functional subscales, and individual symptom scores of the EORTC QLQ-C30. At Week 32, more patients in the ruxolitinib arm (44%) achieved a ≥10-point improvement in global health status/QoL vs. standard therapy (9%). Improvements in MPN-SAF symptom scores were consistent with improvements in EORTC QLQ-C30, PSIS, and PGIC scores. Ruxolitinib provides clinically relevant improvements in QoL and ameliorates symptom burden in patients with PV who are hydroxyurea resistant/intolerant.


Lung Transplant Index: A Quality Improvement Initiative.
Limited long-term survival is a recognized problem in adolescent/young adult lung transplant recipients. A quality improvement (QI) initiative included the development of a Lung Transplant Index (LTI) composed of key elements that we used as a comprehensive approach to screen and identify potential harms in this at-risk patient population. A single-center, uncontrolled QI study was completed from January 2014 to February 2019. The elements of the LTI are events that should have occurred within the most recent 12 months. If an element did not occur, it was counted as a missed element of preventing harm and summated later serving as the LTI score. Implementation of the LTI occurred on January 1, 2015, with a retrospective chart review of patients seen in clinic the prior year serving as baseline measures for comparison. The year before implementing the LTI, numerous opportunities failed to identify preventable harm in our adolescent/young adult lung transplant population. The LTI resulted in a sustained reduction of these missed opportunities without negatively influencing patient/family satisfaction with lengthening of the clinic visit. A single-center QI initiative identified preventable harms in an adolescent/young adult lung transplant population and reduced the number of preventable harm elements not performed. Future work is needed to determine if this type of QI initiative is associated with less healthcare utilization.


The variability of corneal and anterior segment parameters in keratoconus.
To analyse, describe and test diverse corneal and anterior segment parameters in normal and keratoconic eyes to better understand the geometry of the keratoconic cornea. 44 eyes from 44 keratoconic patients and 44 eyes from 44 healthy patients were included in the study. The Pentacam System was used for the analysis of the anterior segment parameters. New ad-hoc parameters were defined by measuring the distances on the Scheimpflug image at the horizontal diameter, with chamber depth now comprising of two distinctive distances: corneal sagittal depth and the distance from the endpoint of this segment to the anterior surface of the lens (DL). Statistically significant differences (p<0.05) between normal and keratoconic eyes were found in all of the analysed corneal parameters. Anterior chamber depth presented statistical differences between normal and keratoconic eyes (3.06±0.43mm versus 3.34±0.45mm, respectively; p=0.004). This difference was found to originate in an increase of the DL distance (0.40±0.33mm in normal eyes against 0.61±0.45mm in keratoconic eyes; p=0.014), rather than in the changes in corneal sagittal depth. These findings indicate that keratoconus results in central and peripheral corneal manifestations, as well as changes in the shape of the scleral limbus. The DL parameter was useful in describing the forward elongation and advance of the scleral tissue in keratoconic eyes. This finding may help in the monitoring of disease progression and contact lens design and fitting.


HPLC studies on the degradation profiles of glucose 5% solutions subjected to heat sterilization in a microprocessor-controlled autoclave.
A practically useful relationship between degradation and F0 at various temperatures is given. This may be of value for identifying the most suitable sterilization conditions for a number of glucose products and other pharmaceuticals. It was found that autoclaving at a high temperature to a low final F0 value gave the maximum product integrity.


A midline retroperitoneal approach for complex abdominal aortic repair: Case description and operative technique.
In the current endovascular era, open repair of complex aortic aneurysms is becoming a rare, but indispensable, part of vascular surgeons' skill set in specific scenarios. For young, low-risk patients and patients with connective tissue disorders, early target vessel bifurcation, a horseshoe kidney, or pedunculated intraluminal aortic thrombus, fenestrated-branched stent graft technology will not be applicable without significant risks. Thus, an open surgical approach has been recommended for these patients. Most vascular surgeons will be familiar with a transperitoneal approach or a retroperitoneal approach with a lateral incision. For patients with a horseshoe kidney, an inflammatory aneurysm, or a history of multiple intraperitoneal procedures, a retroperitoneal approach should be preferred. In the present report, we have described in detail the optimization of a retroperitoneal approach through a midline incision that provides excellent exposure to the paravisceral aorta, improves exposure to the right renal artery and right iliac artery bifurcation (which is limited using the left flank retroperitoneal approach), and avoids division of the lateral abdominal wall muscles, which has often been associated with iatrogenic muscle denervation and postoperative bulging for four patients who had required complex aortic reconstruction.


T cells subtypes in a patient with interferon-alpha induced sarcoidosis.
A 47-year-old woman with a history of blood transfusion-acquired hepatitis C was treated with interferon-alpha when she developed fever, arthralgia, erythema nodosum, dyspnea, and diffuse alveolitis. The diagnosis of IFN-alpha-induced sarcoidosis was retained. The patient's clinical status rapidly improved after IFN-alpha discontinuation, with complete resolution of signs and symptoms. Admission and follow-up assessment of peripheral blood CD4 T cells showed a transient activation process that peaked at 1 to 3 months after onset of symptoms and discontinuation of IFN-alpha. It was marked by a mild increase in activated cells (expressing R-IL2 and HLADR), and a markedly reduced percentage of CD4 T cells expressing the costimulation molecule CD28, ie, an expansion of the CD4CD28 negative subset that is associated with proinflammatory and tissue damaging properties. This activation process also improved over time, but more slowly than clinical symptoms.


[Channel selection for EEG-monitoring in anesthesia].
The conventional multichannel electroencephalogram is quite inconvenient for long-term monitoring in the operating theatre or intensive care unit. Recording of the EEG would be easier if a small number of channels was sufficient. Aiming at reduction of channels, leads from different regions of the scalp were analysed visually and with regard to their spectral content. METHODS. Electrode placements corresponded to the International 10/20 System (Fig. 1). EEG recordings were made with a conventional device (ES 12,000), a personal computer, and a spectral analyser. TWO-CHANNEL RECORDINGS. Retrospective analysis was performed on data from 392 patients (age 14-90 years) whose anaesthesia was induced with various anaesthetics/narcotics, for instance thiopental, ketamine, etomidate, halothane, and enflurane. The EEG was recorded using C3-P3 and Cz-A1. For each patient the changes of spectral parameters during the course of the induction were plotted and visually analysed. For statistical analyses a 30-s epoch of each patient was randomly selected from the first few minutes after the beginning of induction. TEN-CHANNEL RECORDINGS. In ten gynaecological patients (age 26-55 years) EEG recordings were performed during induction of anaesthesia with thiopental in combination with fentanyl, N2O and O2. The set of channels consisted of Fz'-Cb1, F3'-Cb1, Cz-Cb1, C3-Cb1, P3-Cb1, Oz-Cb1, Fz'-F3', F3'-C3, C3-P3, and P3-Oz. The electrodes Fz' and F3' were positioned on the forehead near to Fz and F3, respectively. These sites were chosen because they allow easy application of electrodes. The relationship between channels was calculated with Bravais-Person's coefficient of correlation for the power and the absolute power in the frequency bands delta (0.5-3.5 Hz), theta (3.5-7.5 Hz), alpha (7.5-12.5 Hz), and beta (> 12.5 Hz). RESULTS. In visual and statistical analyses of the two- and ten-channel recordings under the influence of anaesthetics/narcotics, similar changes of EEG activity could be observed in all channels. Although differences in the absolute power of the frequency bands were present, there was high conformity in the composition of the spectral content of the different channels. Classification of the EEG into stages of anaesthesia by means of a single channel led to consistent results for all channels. Alpha activity as leading feature of the awake state predominated occipitally. In channels including the region around the ears, contamination with EKG artifacts was observed. CONCLUSIONS. EEG patterns under the influence of different anaesthetics/narcotics are adequately represented by a reduced number of channels. For the choice of an appropriate set of channels the following aspects should be considered. Contamination with artifacts should be as low as possible, electrode sites should easily be accessible, and special features of the awake state should be identifiable. Experience with routinely conducted EEG recordings in the operating theatre and the intensive care unit showed that the channels C3-P3 or C4-P4 provide a sufficient basis for automatic staging of the depth of anaesthesia, which is implemented in the EEG monitor Narkograph.


Economic burden of hypercholesterolemia in high risk of cardiovascular disease population in Mexico.
To estimate the direct and indirect economic burden of hypercholesterolemia in patients with high risk of a cardiovascular event, specifically there were defined 5 groups of patients: 1) familial hypercholesterolemia; 2, 3 and 4) patients with hypercholesterolemia and background of diabetes, myocardial infarction or stroke; 5) diabetes, myocardial infarction and hypercholesterolemia (very high-risk patients) from the Mexican public healthcare institutions. For the estimation of the direct costs the items included correspond to: outpatient care, pharmacological treatment, inpatient hospital care, and surgical procedures. For indirect economic burden, death certificates, before the end of the productive age due to hypercholesterolemia were calculated (premature mortality). The direct economic burden for the 5 groups of patients at risk is MXN $39,601,464,154 (USD $1,987,526,432), while the indirect economic burden amounts to MXN $121,646,689 (USD $6,105,229). The economic impact of hypercholesterolemia in patients with high cardiovascular risk is $39,723,110,843 (equivalent to USD $1,993,631,661) and corresponds to the 0.16% of GDP.


Slow contractions characterize failing rat hearts.
The reduced power of the failing heart can be ascribed to a combination of reduced force and slower contraction. We hypothesized that these two properties are due to different cellular mechanisms. We measured contraction parameters both in vivo and in isolated left ventricular (LV) cardiomyocytes from a rat model of post infarction congestive heart failure (CHF). ECG was measured simultaneously with echocardiography and LV pressure, respectively. Shortening and shortening velocity (SV) in isolated cardiomyocytes were measured during different stimulation protocols. LV end diastolic pressure (LVEDP) was 24.6 +/- 0.7 mmHg in CHF. LV systolic pressure was decreased by 20%, maximum rate of pressure development in the LV (+dP/dtmax) by 36% and time in systole increased by 20% in CHF compared to sham. Electrical remodelling occurred in CHF cells, which were depolarized and had prolonged action potentials (AP) compared to sham cells. Fractional shortening (FS) was increased in CHF compared to sham independent of stimulation protocol. Larger FS was accompanied by increased sarcoplasmic reticulum (SR) Ca2+ load and depended on the electrical remodelling. Time to peak contraction (TTP) was increased in CHF compared to sham cells, but in contrast to FS, TTP was only slightly affected when the cells were stimulated with sham APs and sham diastolic membrane potential (DMP). Contraction duration (corresponding to systolic duration) was 25% longer in CHF than in sham independent on stimulation protocol. We conclude that electrical remodelling affecting DMP and AP duration (APD) significantly affects the size of contraction, whereas the mechanism for slowing of contraction in CHF is different.


Cancellous bone changes in hip osteoarthritis: a short-term longitudinal study using fractal signature analysis.
To quantify changes to the trabecular structure in the femoral heads of patients with hip osteoarthritis (OA). Patients with OA (n=14; F=7), mean (standard deviation age) 50.6 (10.1) years, had macroradiographs at approximately x4 magnification at baseline and 18 months later using a standardized protocol. Following digitization, computerized measurement was obtained of minimum hip joint space width and fractal signature analysis (FSA) measured longitudinal changes separately in the principal compressive (vertical) and horizontal trabeculae at the region of interest within the centre of the head. The patient group had mean annual rate of joint space narrowing of 0.14+/-0.36 mm/yr. FSA detected no significant changes in horizontal trabeculae, whereas the larger principal compressive (vertical) trabeculae (0.96 mm to 1.02 mm) increased significantly in thickness and the fine to medium trabeculae (0.18 mm to 0.54 mm) decreased significantly in number. The increased thickness of the larger trabeculae within the compressive structural element of the femoral head is a response to the increase in stress associated with an overall loss of trabeculae in this region, suggesting the presence of an osteoporosis within the femoral head in OA patients.


Accurate positioning of magnetic microparticles beyond the spatial resolution of clinical MRI scanners using susceptibility artifacts.
Susceptibility-based negative contrast in magnetic resonance imaging (MRI) provides a mean to visualize magnetic microparticles. In the presence of a number of microparticles in the field of view (FOV), the shape of the artifact is affected by the dipole-dipole interaction between the particles. Due to the limited spatial resolution of the clinical MR scanners, the exact positioning of the particles in MR images is not possible. However, the shape of the artifact can shed light on how the particles are distributed within the FOV. In this work, a simulation model and in-vitro experiments were used to study the shape and the amount of the susceptibility artifact for various spacing and angulations between the microparticles. The results showed that for a pair of identical particles with a diameter of D, the signal loss starts to change when particles are separated ~15 × D and they become fully distinguishable when their distance reaches ~ 40 × D.


Plasma Genotyping at the Time of Diagnostic Tissue Biopsy Decreases Time-to-Treatment in Patients With Advanced NSCLC-Results From a Prospective Pilot Study.
The availability of targeted therapies has transformed the management of advanced NSCLC; however, most patients do not undergo guideline-recommended tumor genotyping. The impact of plasma-based next-generation sequencing (NGS) performed simultaneously with diagnostic biopsy in suspected advanced NSCLC has largely been unexplored. We performed a prospective cohort study of patients with suspected advanced lung cancer on the basis of cross-sectional imaging results. Blood from the time of biopsy was sequenced using a commercially available 74-gene panel. The primary outcome measure was time to first-line systemic treatment compared with a retrospective cohort of consecutive patients with advanced NSCLC with reflex tissue NGS. We analyzed the NGS results from 110 patients with newly diagnosed advanced NSCLC: cohorts 1 and 2 included 55 patients each and were well balanced regarding baseline demographics. In cohort 1, plasma NGS identified therapeutically informative driver mutations in 32 patients (58%) (13 KRAS [five KRAS G12C], 13 EGFR, two ERRB2, two MET, one BRAF, one RET). The NGS results were available before the first oncology visit in 85% of cohort 1 versus 9% in cohort 2 (p < 0.0001), with more cohort 1 patients receiving a guideline-concordant treatment recommendation at this visit (74% versus 46%, p = 0.005). Time-to-treatment was significantly shorter in cohort 1 compared with cohort 2 (12 versus 20 d, p = 0.003), with a shorter time-to-treatment in patients with specific driver mutations (10 versus 19 d, p = 0.001). Plasma-based NGS performed at the time of diagnostic biopsy in patients with suspected advanced NSCLC is associated with decreased time-to-treatment compared with usual care.


Mechanical failure of hydroxyapatite- and polysulfone-coated titanium rods in a weight-bearing canine model.
Three types of material that have shown potential as coatings for orthopaedic implants were studied. Using a weight-bearing canine model, Ti-6A1-4V femoral intramedullary rods coated with (1) sintered titanium beads, (2) plasma-sprayed hydroxyapatite, and (3) silyl coupled polysulfone beads were evaluated for mechanical strength and bone ingrowth. The model was designed to secure optimal prosthetic stability by obtaining maximal bony ingrowth during an initial non-weight-bearing phase, then stressing the implant during a full-weight-bearing phase. None of the rods coated with titanium beads failed. All 17 polysulfone-coated rods failed, 13 of them at the interface between the polysulfone coating and the titanium core. Of 18 rods coated with hydroxyapatite, 15 suffered implant breakdown at the interface between the hydroxyapatite coating and the titanium core. This may be due to dissolution of the plasma-sprayed hydroxyapatite in vivo. Testing of retrieved specimens from both hydroxyapatite- and polysulfone-coated implants showed that the shear strength at the coating-rod interface had decreased to less than 40% of the shear strength at manufacture. Despite mechanical failure, histologic study showed extensive bone ingrowth or apposition onto both the polysulfone and hydroxyapatite coatings.


Diabetes guidelines, outcomes, and cost-effectiveness study: a protocol, prototype, and paradigm.
It is a milestone for our profession to have practice guidelines tested in a clinical trial that also provides cost-effectiveness data. Dietetics practitioners now have a model for studies examining MNT in other disorders and diseases. We also have an array of questions that can be asked in future studies. The challenges include examining the long-term management of diseases using MNT; determining changes in quality-of-life issues; and segmenting subjects according to variables likely to affect outcomes, such as duration of the disease. As a result of this and other studies related to diabetes (both completed and in progress), millions of people with NIDDM will be guided to achieve the best glycemic control possible within the framework of their lifestyles. The results of the DCCT may have implications for persons with NIDDM (18), as well as for dietitians (8). The UK Prospective Diabetes Study results should be released in the near future (19), and the VA Cooperative Study on Glycemic Control and Complications in Type II Diabetes (20) is examining intensive therapy for this population. Each of these studies emphasizes a treatment approach that places management of the disease in the hands of the client. This approach clearly is a paradigm shift: no longer are we talking about "diabetic diets." But then, maybe we just need to read a little history. In 1906, Hutchison (21) wrote," ... there is no such thing as 'a diabetic diet.'" And think about the information (or lack thereof) available to him.


Extrahepatic morbidities and mortality of NAFLD: an umbrella review of meta-analyses.
Nonalcoholic fatty liver disease (NAFLD) has reached pandemic proportions currently and may contribute to multiple extrahepatic outcomes. To comprehensively summarise evidence of associations between NAFLD and risk of extrahepatic outcomes. We conducted an umbrella review. We searched PubMed, Web of Science and Cochrane database from inception to 27 November 2021. We included 22 meta-analyses with 374 original studies in our analysis. Subjects with NAFLD had an increased risk of mortality, multiple cardiovascular complications, extrahepatic cancers, diabetes and chronic kidney disease (CKD) than those without NAFLD. Excess risks of several other extrahepatic outcomes including hypothyroidism, urolithiasis, gastro-oesophageal reflux disease, gallstones, depression and worse maternal and foetal outcomes were also observed in this population. However, associations were not significant for prostate cancer, female organ genital cancer, haematological cancer, diabetic retinopathy or osteoporotic fracture. The risks of CVD, diabetes and CKD were similar in obese and non-obese patients. Most associations were heterogeneous across regions; significantly, Europeans with NAFLD were more prone to all-cause mortality than North Americans. The certainty of evidence was graded from only very low to moderate as all included studies were observational. Patients with NAFLD are at heightened risk of extrahepatic outcomes. However, the certainty of evidence is only from very low to moderate. Further studies at low risk of bias are required to support the evidence and elucidate any causal associations.


Labisia pumila protects the bone of estrogen-deficient rat model: a histomorphometric study.
Labisia pumila var. alata (LP) is a phytoestrogenic herb with potential as an alternative to Estrogen Replacement Therapy (ERT) in the treatment of postmenopausal osteoporosis. LP has been reported to produce similar effects to ERT on the bone markers, but could not match ERT in terms of maintaining the bone calcium in postmenopausal osteoporosis rat model. This study aimed to examine in detail the effects of LP on the bone of postmenopausal osteoporosis rat model using bone histomorphometry. Thirty two female rats were randomly divided into groups of: Sham operated (Sham), ovariectomized control (OVXC), ovariectomized with Labisia pumila var. alata (LP) and ovariectomized with ERT (Premarin®) (ERT). The LP and ERT were administered through the route of oral gavage daily at the dose of 17.5 mg/kg and 64.5 μg/kg respectively. Following 2 months of treatment, rats were euthanized and the left femurs were dissected out and prepared for bone histomorphometry. Histomorphometric analysis revealed osteoporotic changes for the ovariectomized rats. Supplementation of LP to ovariectomized rats could prevent these osteoporotic changes, as effective as ERT. This confirmed that LP has potential as an alternative to ERT for prevention of postmenopausal osteoporosis.


Evaluation and statistical judgement of neural responses to sinusoidal stimulation in cases with superimposed drift and noise.
Time histograms of neural responses evoked by sinuosidal stimulation often contain a slow drifting and an irregular noise which disturb Fourier analysis of these responses. Section 2 of this paper evaluates the extent to which a linear drift influences the Fourier analysis, and develops a combined Fourier and linear regression analysis for detecting and correcting for such a linear drift. Usefulness of this correcting method is demonstrated for the time histograms of actual eye movements and Purkinje cell discharges evoked by sinusoidal rotation of rabbits in the horizontal plane. In Sect. 3, the analysis of variance is adopted for estimating the probability of the random occurrence of the response curve extracted by Fourier analysis from noise. This method proved to be useful for avoiding false judgements as to whether the response curve was meaningful, particularly when the response was small relative to the contaminating noise.


The treatment of resistant warts with intralesional bleomycin: a controlled clinical trial.
A controlled double-blind trial was carried out on fifty-nine matched pairs of hand warts in a group of twenty-four patients, with proven resistance to treatment, to study the effectiveness of the intralesional injection of 0.1% solution of bleomycin sulphate in normal saline, compared with a normal saline placebo injected into the paired warts in the same patient. We found that 87.5% of patients showed a more favourable response to bleomycin (P less than 0.001); 76% of the fifty-nine warts treated with bleomycin were cured by one to three injections of up to 0.2 ml of solution. Subsequently 75% of thirty-two patients with resistant hand warts and 66% of fifteen patients with mosaic plantar warts were cured of all their warts. No patient received more than 4 mg of bleomycin. No toxicity was experienced. Local pain was on the whole well tolerated. This form of treatment for resistant warts is reliable, safe and acceptable to patients.


Adverse effects of topical antiglaucoma drugs on the ocular surface.
This study was designed to determine the effect of long-term antiglaucoma topical medication on the ocular surface; measuring basal Schirmer's and tear break-up time tests using conjunctival impression cytology. The ocular surfaces of 30 control subjects (group 1), 24 primary open-angle glaucoma patients treated with 0.5% betaxolol hydrochloride (group 2), 27 primary open-angle glaucoma patients treated with 0.5% timolol maleate (group 3) and 26 primary open-angle glaucoma patients treated with 0.5% betaxolol and 1% dipivefrin hydrochloride (group 4) were evaluated. Basal Schirmer's and tear break-up time tests were measured and ocular surface changes were determined by impression cytology. Impression cytology specimens of each group were graded and scored in the range 0-3 according to Nelson's method. Patients in groups 2, 3 and 4 showed statistically significant fewer normal basal Schirmer's tests (wettability) and tear break-up time tests (P < 0.01). Also, the conjunctival impression cytology scores were significantly higher in groups 2, 3 and 4 than in group 1 (P < 0.01). The conclusion was that it is possible that conjunctival surface and tear film function change after the long-term use of antiglaucoma medication.


Urotensin II induction of neonatal cardiomyocyte hypertrophy involves the CaMKII/PLN/SERCA 2a signaling pathway.
Although studies have shown that Urotensin II (UII) can induce cardiomyocyte hypertrophy and UII-induced cardiomyocyte hypertrophy model has been widely used for hypertrophy research, but its precise mechanism remains unknown. Recent researches have demonstrated that UII-induced cardiomyocyte hypertrophy has a relationship with the changes of intracellular Ca(2+) concentration. Therefore, the aim of this study was to investigate the mechanisms of cardiomyocyte hypertrophy induced by UII and to explore whether the calcium/calmodulin-dependent protein kinase II (CaMKII)-mediated up-regulating of phospholamban (PLN) Thr17-phosphorylation signaling pathway contributed to UII-induced cardiomyocyte hypertrophy. Primary cultures of neonatal rat cardiomyocytes were stimulated for 48h with UII. Cell size, protein/DNA contents and intracellular Ca(2+) were determined. Phosphorylated and total forms of CaMKII, PLN and the total amount of serco/endo-plasmic reticulum ATPases (SERCA 2a) were quantified by western blot. The responses of cardiomyocytes to UII were also evaluated after pretreatment with the CaMKII inhibitor, KN-93. These results showed that UII increased cell size, protein/DNA ratio and intracellular Ca(2+), consistent with a hypertrophic response. Furthermore, the phosphorylation of CaMKII and its downstream target PLN (Thr17), SERCA 2a levels were up-regulated by UII treatment. Conversely, treatment with KN-93 reversed all those effects of UII. Taken together, the results suggest that UII can induce cardiomyocyte hypertrophy through CaMKII-mediated up-regulating of PLN Thr17-phosphorylation signaling pathway.


Factors associated with the premature graduation of children into seatbelts.
This study investigated the factors associated with the premature graduation into seatbelts for Australian children aged 4-11 years. From 699 child restraint use questionnaires, 195 children were identified as meeting the booster seat height-weight criteria (height: 100-145 cm and weight: 14-26 kg). Of these children, 44% were correctly traveling in a booster seat, while 56% had been moved prematurely into a seatbelt. A multivariable logistic regression model showed that there were a number of key predictors associated with the premature graduation to seatbelts. For example, children who were moved prematurely into a seatbelt were more likely to be older, have other children travelling in the vehicle and have younger parents compared to children appropriately restrained in a booster seat. In addition, there was a significant interaction between vehicle type and parent's household income. Based on the findings of this study, a number of recommendations are made for strategies to enhance appropriate restraint use for this age group, as well as for future research.


Preparation of pH-sensitive, long-circulating and EGFR-targeted immunoliposomes.
A long-circulating formulation of pH-sensitive liposomes (PSLs) with antibodies against epidermal growth factor receptor (EGFR) attached was designed, expecting an increase in binding and delivery of liposomes to the target cells including non-small cell lung cancer (NSCLC) cells. Physicochemical properties of the PSLs were measured by SEM and DLS. Leakage of a self-quenching fluorescent probe, calcein, from the liposome was studied for the evaluation of pH-sensitivity. Encapsulation efficiency of gemcitabine (an anti-cancer drug) in PSLs was about 67%. Average size of liposomes was 88 nm in diameter. The PSL of DOPE/CHEMS (6:4 molar ratio) formulation showed a dramatic pH-sensitivity at/around pH 5.5, whereas non-PSL of DPPC/Chol or PC/CHEMS formulation did not. Anti-proliferation effect of gemcitabine-encapsulating PSLs & Ab-PSLs in A549 cells was 2-fold higher than the free drug, which was further elucidated by the apoptosis of the cells by gemcitabine (approximately 10% apoptosis for PSL or Ab-PSL formulation vs. approximately 1% for free drug or non-PSL formulation) using FACS analysis. These data demonstrate delivery of gemcitabine to tumor cells can be improved by long-circulating PSLs or Ab-PSLs formulations in vitro.


Ultimate pH effects on dry-aged beef quality.
This study aimed to evaluate pH effects on moisture loss and meat quality characteristics of dry-aged beef. Strip loins from six normal pH carcasses (pH = 5.47 ± 0.02) and dark cutting (DC) strip loins from six high pH carcasses (pH = 6.69 ± 0.09) were obtained. One strip loin from each carcass was dry aged and one was wet aged, giving four treatments: DRY, DRY-DC, WET, and WET-DC. Loins were aged for 42 d. Ultimate pH did not affect the rate or amount of moisture loss, trim loss, yield, or tenderness in dry-aged beef (P > 0.05). In general, DC steaks had the lowest lightness (L*), redness (a*), and yellowness (b*) values, regardless of aging method (P < 0.05). Discoloration scores and TBARS values for DC steaks remained low throughout retail display. Dry aging significantly reduced bacterial counts mitigating the microbial damages associated with DC. Flavor characteristics of DC were not improved by dry aging when compared to dry-aged loins from carcasses with normal pH.


Glutathione and Bcl-2 targeting facilitates elimination by chemoradiotherapy of human A375 melanoma xenografts overexpressing bcl-xl, bcl-2, and mcl-1.
Bcl-2 is believed to contribute to melanoma chemoresistance. However, expression of Bcl-2 proteins may be different among melanomas. Thus correlations among expression of Bcl-2-related proteins and in vivo melanoma progression, and resistance to combination therapies, was investigated. Human A375 melanoma was injected s.c. into immunodeficient nude mice. Protein expression was studied in tumor samples obtained by laser microdisection. Transfection of siRNA or ectopic overexpression were applied to manipulate proteins which are up- or down-regulated, preferentially, during melanoma progression. Anti-bcl-2 antisense oligonucleotides and chemoradiotherapy (glutathione-depleting agents, paclitaxel protein-binding particles, daunorubicin, X rays) were administered in combination. In vivo A375 cells down-regulated pro-apoptotic bax expression; and up-regulated anti-apoptotic bcl-2, bcl-xl, and mcl-1, however only Bcl-2 appeared critical for long-term tumor cell survival and progression in vivo. Reduction of Bcl-2, combined with partial therapies, decreased melanoma growth. But only Bcl-2 targeting plus the full combination of chemoradiotherapy eradicated A375 melanoma, and led to long-term survival (> 120 days) without recurrence in 80% of mice. Tumor regression was not due to immune stimulation. Hematology and clinical chemistry data were within accepted clinical toxicities. Strategies to target Bcl-2, may increase the effectiveness of antitumor therapies against melanomas overexpressing Bcl-2 and likely other Bcl-2-related antiapoptotic proteins.


Studies on the phylogenesis of pathogenic 'black yeasts'.
This paper deals mainly with the conidium ontogenesis and phylogenesis of black yeasts such as E. jeanselmei, E. gougerotii, E. dermatitidis and E. spinifera. The conidium ontogenesis of E. jeanselmei, E. gougerotii and E. dermatitidis was almost the same. One to five annellated tips were observed through a scanning microscope at the apices of conidiogenous cells, which were bottle- or jar-shaped. Annellations on the tips looked like fringes and the conidiogenous cells of these three species were annellides. Annellated projections occurred on hyphae and annelloconidia were also produced from them. Occasionally, secondary annellides occurred from primary ones. They looked like moniliform hyphae. Daughter conidia sometimes budded directly from mother cells. The shapes and sizes of the conidia of these species were very similar to each other. The conidium ontogenesis of E. spinifera was annellidic as well. However, a single annellated tip usually occurred on an annellide. The annellated tips of the fungus were long and more than 20 annellations were observed on their walls. The conidiogenesis of the four species of Exophiala is only annellidic. There were no differences in the biological examinations except KNO3 assimilation among these four species. The growth of E. jeanselmei and E. gougerotii was poor at 37 degrees C. The GC contents of E. jeanselmei 1171, E. gougerotii B-1800, E. dermatitidis MM-7 and E. spinifera DU-3342 were 54.6, 54.6, 56.6 and 59.7%, respectively.


Boswellic acids as promising agents for the management of brain diseases.
Boswellic acid (BA)s are pentacyclic triterpenic acids present in gum resin of Boswellia species (such as B. serrata and B. carterii). They possess a variety of pharmacological effects such as anti-inflammatory, anti-oxidant, and anti-excitotoxic effects. These properties may have potential therapeutic implication in neurological disorders. Notably, the BAs-induced neuroprotection is proposed to be associated with the ability to reduce neurotoxic aggregates, decrease oxidative stress, and improve cognitive dysfunction. Recently, BAs have been suggested as potential agents for the treatment of brain tumors due to their potential to attenuate cell proliferation, migration, metastasis, angiogenesis, and promote apoptosis during both in vitro and in vivo studies. The present review aims to address these studies and highlights the possible underlying mechanisms of the observed effects. Besides, novel formulations and improving pharmacokinetic properties may enhance the therapeutic efficacy of BAs.


Reduced capillary permeability and capillary density in the skin of GH-deficient adults: improvement after 12 months GH replacement.
Several lines of evidence suggest that the GH-IGF-1 axis affects capillary permeability and angiogenesis. We evaluated skin capillary permeability and capillary density in GH-deficient adults, before and after GH replacement therapy. Seven normotensive, nondiabetic GH-deficient adults (two women) were matched with 14 control subjects. Large-window videodensitometry with sodium fluorescein was performed in all subjects. Capillary permeability was expressed as the average relative light intensity over the first 7 min after the appearance of fluorescein in the skin capillaries; Iav(7). Skin capillary density was determined by counting the visualized capillaries and was expressed as n/mm2. The GH-deficient patients were restudied after 12 months of GH replacement therapy (2 U/day). Both capillary permeability and capillary density were lower in untreated GH-deficient patients than in control subjects (median, interquartile range): Iav(7) in GH-deficient patients 47.1 (45.1-52.2)% vs. 57.5 (50.5-64.8)% in controls, P < 0.05; capillary density in GH-deficient patients 18 (12-24)/mm2 vs. 32 (26-36)/mm2 in controls, P < 0.05. GH treatment normalized plasma IGF-1 from 4.3 (1.0-13.4) to 22.2 (19.8-48.2) nmol/l (P < 0.05). Furthermore, both capillary permeability [Iav(7) 53.1 (48.8-58.4)%, P < 0.05] and capillary density [26 (17-34)/mm2, P < 0.05] increased to a level that was not different from that in control subjects. The present study demonstrates that the growth hormone deficiency syndrome is associated with microvascular alterations, which are responsive to growth hormone replacement therapy.


Predictive clinical factors for the differential diagnosis of childhood extratemporal seizures.
To describe predictive clinical factors for the differentiation between childhood frontal lobe epilepsy (FLE) and posterior cortex epilepsy (PCE). Two independent, blinded investigators analyzed 177 seizures from 35 children (aged 11 months to 12 years) with extratemporal epilepsy selected by postoperative seizure-free outcome. Semiologic seizure components and different periictal signs were observed. Age at onset, auras, seizure frequency, and nocturnal dominance, as well as surgical and histopathologic data, were collected from medical charts. Twenty patients had FLE, and 15 had PCE. Patients from both groups had daily seizures without significant differences in frequency but with higher nocturnal dominance in children with FLE (p < 0.05). Visual aura, nystagmus, and versive seizure were observed exclusively in the PCE group, whereas somatosensory aura and hypermotor seizures appeared only in FLE. Tonic seizures were significantly more frequent in FLE (p < 0.01), whereas the presence of clonic seizure (FLE; p = 0.07) and postictal nose-wiping (PCE; p = 0.05) showed only a trend to localize the seizure-onset zone. Myoclonic seizures, epileptic spasms, psychomotor seizures, atonic seizures, oral and manual automatisms, as well as vocalization and eye deviation appeared in both groups without significant differences in their frequency. Characteristic features described in adults' extratemporal epilepsies were frequently missing during childhood seizures, especially in infants and preschool children. Ictal features help only a little in differentiating childhood FLE from PCE. Nocturnal appearance and the type of aura have high localizing value; therefore an accurate history taking is still an essential element of pediatric presurgical evaluation.


The effect of transforming growth factor-beta on mechanical properties of the fibrous tissue regenerated in the patellar tendon after resecting the central portion.
No investigators have studied the effects of an application of growth factors on the in vivo tissue regeneration in the tendon after resecting the central portion. The purpose of this study is to clarify whether an application of transforming growth factor (TGF)-beta1 increases the mechanical properties of the regenerated tissue in the patellar tendon after resecting the central portion. Thirty female rabbits were divided into three groups, after a 3 mm wide and 10 mm long tendon substance was resected from the central portion in the patellar tendon. In Group I, 5-ng TGF-beta1 dissolved in 0.1-ml saline was injected into the resected portion in the patellar tendon. In Group II, only 0.1-ml saline was injected into the resected portion. In Group III, nothing was injected. All animals were sacrificed at 6 weeks after surgery. Mechanical and histological evaluations were made concerning the regenerated tissue and the unresected tendon tissue in the patellar tendon. Concerning the regenerated tissue, the tangent modulus and the tensile strength of Group I were significantly greater than those of Groups II and III, while there were no significant differences in these parameters between Groups II and III. The application of TGF-beta1 significantly increases the tangent modulus and the tensile strength of the fibrous tissue regenerated in the patellar tendon after resecting the central portion. This study has provided basic important information on the utility of TGF-beta1 in the in vivo tendon regeneration.


SnapShot: Key Advances in hiPSC Disease Modeling.
This SnapShot presents a timeline of key advances in directed differentiation and disease modeling using human pluripotent stem cells. The selected papers are color-coded for different systems and show progress in the field, from making disease- and tissue-specific hiPSC derivatives to the development of disease models for drug screening and therapeutics and the generation of complex systems that mimic tissue architecture and self-organized structures. To view this SnapShot, open or download the PDF.


Spatial vectorcardiography in the Wolff-Parkinson-White syndrome: correlation with epicardial mapping findings.
The spatial vectorcardiograms (VCG) of 13 patients with WPW syndrome due to single accessory pathways were analyzed and correlated with the excitation analysis obtained on epicardial mapping. The azimuth angle of the initial 10 ms cardiac vector was greater than + 90 degrees (directed right and anteriorly) in patients with a left ventricular free wall; it ranged between 0 degree to 90 degrees (left and anteriorly) in those with a left or right paraseptal free wall and was -30 degrees (left and posteriorly) in one patient with a right ventricular free wall location. The elevation angle of the initial 10 and 20 ms cardiac vector was either zero or positive (inferiorly directed) in those with right and left ventricular free wall pathway. Among six patients with a paraseptal location, the elevation angle was negative (superiorly directed) in four and positive in two. Both the patients with a clockwise inscription of a QRS loop in the horizontal plane (HP) had pathways located to the left ventricle. Among the paraseptal group, at surgery, the accessory pathway could not be excised in two in spite of dissection very close to the IV (interventricular) septum. The elevation angle in both these patients was markedly negative (-45 degrees and -62 degrees) in contrast to the other in whom surgical excision was successful.+


Protective action of Lactobacillus kefir carrying S-layer protein against Salmonella enterica serovar Enteritidis.
Eight Lactobacillus kefir strains isolated from different kefir grains were tested for their ability to antagonize Salmonella enterica serovar Enteritidis (Salmonella enteritidis) interaction with epithelial cells. L. kefir surface properties such as autoaggregation and coaggregation with Salmonella and adhesion to Caco-2/TC-7 cells were evaluated. L. kefir strains showed significantly different adhesion capacities, six strains were able to autoaggregate and four strains coaggregated with Salmonella. Coincubation of Salmonella with coaggregating L. kefir strains significantly decreased its capacity to adhere to and to invade Caco-2/TC-7 cells. This was not observed with non coaggregating L. kefir strains. Spent culture supernatants of L. kefir contain significant amounts of S-layer proteins. Salmonella pretreated with spent culture supernatants (pH 4.5-4.7) from all tested L. kefir strains showed a significant decrease in association and invasion to Caco-2/TC-7 cells. Artificially acidified MRS containing lactic acid to a final concentration and pH equivalent to lactobacilli spent culture supernatants did not show any protective action. Pretreatment of this pathogen with spent culture supernatants reduced microvilli disorganization produced by Salmonella. In addition, Salmonella pretreated with S-layer proteins extracted from coaggregating and non coaggregating L. kefir strains were unable to invade Caco-2/TC-7 cells. After treatment, L. kefir S-layer protein was detected associated with Salmonella, suggesting a protective role of this protein on association and invasion.


New Treatment Options for Mycosis Fungoides.
The article discusses imiquimod treatment for refractory early stage mycosis fungoides, with a review of the literature and three case studies.


Affinity capillary electrophoresis applied to the studies of interactions of a member of heat shock protein family with an immunosuppressant.
The bioaffinity of receptor-ligand interactions is investigated by determining the binding constant (association constant or dissociation constant) of the resulting complex utilizing affinity capillary electrophoresis (ACE). The ACE binding assay was established with a potent immunosuppressant, deoxyspergualin (DSG), that binds specifically to Hsc70, a constitutive or cognate member of heat shock protein 70 (Hsp70) family. Quantitative determination of binding constants under different running buffer systems provide comparative results. The association constants for the interaction between Hsc70 protein and DSG were found to be 5.7 x 10(4) M-1 in a buffer with pH 6.95 and 6.3 x 10(4) M-1 in a buffer with pH 5.30 (or corresponding dissociation constants, 18 and 16 microM, respectively) based on Scatchard analyses. Binding of DSG to a synthetic peptide, SINPDEAVAYGAAVQAAILSGDK, one of the DSG-binding fragments found from tryptic digest of Hsc70 protein, provides further detailed information for the understanding of Hsc70 binding domain. The applicability of using coated capillaries was also evaluated for probing Hsc70-DSG interaction.


Reliability of dynamometric measurements of the pelvic floor musculature.
The objective of this study was to evaluate the reliability of strength and endurance dynamometric measurements of the pelvic floor musculature (PFM). Twenty-nine female participants, primipara and multipara, aged between 27 and 42 and presenting different severity levels of stress urinary incontinence (SUI), participated in the study. They were evaluated using a new pelvic floor dynamometer, an instrumented speculum based on strain-gauged technology. Strength and endurance evaluations were repeated in three successive sessions, each followed by a 4-week period. Maximal strength values were recorded at three dynamometer openings (5 mm, 1 cm, and 1.5 cm between the two dynamometer branches). The maximal rate of force development (MRFD) and percentage of strength lost after 10 and 60 sec were computed from the endurance trial. The generalizability theory was applied to estimate the reliability of the PFM measurements. The reliability was quantified by the index of dependability and the corresponding standard error of measurement (SEM) for one and the mean of three trials performed in one session for the strength measurements and one trial completed in one session for the MRFD and endurance measurements. For the maximal strength measurements, the largest coefficient of dependability was obtained at the 1 cm opening, with a value of 0.88. The corresponding SEM reached 1.49 N. The reliability of the MRFD was also very good with a coefficient of 0.86 and an SEM of 0.056 N/sec. The reliability was minimally affected by the number of trials. The strength loss measurements at 10 and 60 sec were unreliable, with coefficient values of 0.38 and 0.10, respectively. The results of the present study indicate that the reliability of the strength parameters (maximal strength and MRTD measurements) was high enough for future investigations on pelvic floor rehabilitation programs.


Observation-based global soil heterotrophic respiration indicates underestimated turnover and sequestration of soil carbon by terrestrial ecosystem models.
Soil heterotrophic respiration (Rh ) refers to the flux of CO2 released from soil to atmosphere as a result of organic matter decomposition by soil microbes and fauna. As one of the major fluxes in the global carbon cycle, large uncertainties still exist in the estimation of global Rh , which further limits our current understanding of carbon accumulation in soils. Here, we applied a Random Forest algorithm to create a global data set of soil Rh , by linking 761 field observations with both abiotic and biotic predictors. We estimated that global Rh was 48.8 ± 0.9 Pg C year-1 for 1982-2018, which was 16% less than the ensemble mean (58.6 ± 9.9 Pg C year-1 ) of 16 terrestrial ecosystem models. By integrating our observational Rh with independent soil carbon stock data sets, we obtained a global mean soil carbon turnover time of 38.3 ± 11 year. Using observation-based turnover times as a constraint, we found that terrestrial ecosystem models simulated faster carbon turnovers, leading to a 30% (74 Pg C) underestimation of terrestrial ecosystem carbon accumulation for the past century, which was especially pronounced at high latitudes. This underestimation is equivalent to 45% of the total carbon emissions (164 Pg C) caused by global land-use change at the same time. Our analyses highlight the need to constrain ecosystem models using observation-based and locally adapted Rh values to obtain reliable projections of the carbon sink capacity of terrestrial ecosystems.


Bone plug length and loading angle determine the primary stability of patellar tendon-bone grafts in press-fit ACL reconstruction.
The present study was conducted to evaluate the influence of bone-plug length on the primary stability of patellar tendon-bone grafts, using a femoral press-fit fixation technique. Forty-eight human PTB grafts with a patellar bone-plug length of 15 mm and 25 mm were obtained from 24 human cadavers (mean age 72 years) and implanted to porcine femora in a press-fit fixation technique. Tensile loading was performed at 10 mm/s until failure at varying loading angles of 0 degrees, 30 degrees and 60 degrees. Compared to 25 mm, a significant decrease of primary graft stability was recorded in the testing of 15-mm bone plugs. For both plug lengths, the ultimate load to failure increased with rising the loading angles. While axial graft loading exclusively caused plug dislocation, the predominant mode of failure was tendon rupture at 60 degrees loading angle. We conclude that 15-mm bone plugs do not result in a sufficient stability for early aggressive rehabilitation and therefore 25-mm bone plugs are recommended for the femoral press-fit technique.


Evaluation of two rapid screening assays for detecting hepatitis C antibodies in resource-constrained settings.
To evaluate the diagnostic accuracy of the OraQuick HCV rapid antibody test from OraSure and the Multisure HCV antibody assay from MP Biomedicals. Five seropanels from patients, intravenous drug users and blood donors with and without HCV infection were used on the two rapid immunochromatographic tests. Sensitivity, specificity and predictive values were calculated. In addition, seropanels from 10 seroconverters were used to assess early identification of HCV infection. The study was undertaken in a laboratory at Paul Ehrlich Institute in Germany. Panel 1 contained of 55 positive and 25 negative samples. The OraQuick HCV test had a sensitivity of 100% (95% CI: 93.5-100) and a specificity of 100% (95% CI: 86.3-100). The Multisure HCV test had a sensitivity of 100% (95% CI: 93.5-100) and a specificity of 96% (95% CI: 79.6-99.9). Panel 2 consisted of 193 pre-characterised anti-HCV-positive patient samples. The OraQuick HCV test identified 191 samples correctly and the Multisure HCV 192. The sensitivity was 99.0% (95% CI: 96.3-99.9) for the OraQuick HCV test and 99.5% (95% CI: 97.1-100) for the Multisure HCV test. Panel 3 was composed of seroconversion samples of 10 patients. The OraQuick HCV test detected all of these 10 infections while the Multisure HCV test detected six and was indeterminate on 2. Panel 4 included 53 anti-HCV negative blood samples from blood donors. Both tests correctly identified all 53. Panel 5 consisted of 26 samples of HCV/HIV co-infected patients. The sensitivity of the OraQuick HCV test was 65.2% (95% CI: 42.8-82.8) after 20 min and 73.9% (95% CI: 51.3-88.9) after 40 min of incubation. The Multisure HCV test had a sensitivity of 96.2% (95% CI: 80.4-99.9). This evaluation revealed good sensitivity for both rapid screening assays. The detection of seroconverters, however, was lower in the MutiSure HCV test. Therefore the MultiSure test should be used with hesitation in high incidence settings. The OraQuick gave HCV false-negative results in almost 25% of the HIV-positive sera. Therefore may the OraQuick be less suited in HIV prevalent areas.


The ability of herpes simplex virus type 1 immediate-early protein Vmw110 to bind to a ubiquitin-specific protease contributes to its roles in the activation of gene expression and stimulation of virus replication.
Herpes simplex virus type 1 immediate-early protein Vmw110 stimulates the onset of virus infection and is required for efficient reactivation from latency. In transfection assays, Vmw110 is a potent activator of gene expression, but its mode of action has yet to be determined. Previous work has shown that Vmw110 localizes to specific intranuclear structures known as ND10, PML bodies, or PODs and causes the disruption of these domains. The ability of Vmw110 to disrupt ND10 correlates with its biological activities in infected and transfected cells. It has also been found that Vmw110 binds strongly and specifically to a ubiquitin-specific protease known as HAUSP, itself a component of a subset of ND10. In this study we have investigated the role of HAUSP in Vmw110 activity; single amino acid residues of Vmw110 required for the interaction were identified, and the effects of mutation of these residues in infected and transfected cells were then assayed. The results indicate that the ability to bind to HAUSP contributes to the functional activities of Vmw110.


Surface characterization, in vitro and in vivo biocompatibility of Mg-0.3Sr-0.3Ca for temporary cardiovascular implant.
Magnesium-based alloys are attractive candidate materials for medical applications. Our earlier work showed that the ternary Mg-0.3Sr-0.3Ca alloy exhibits slower degradation rates than both binary Mg-Sr and Mg-Ca alloys. The ternary alloy immersed in simulated body fluid (SBF) forms a compact surface layer of corrosion products that we hypothesized to be a Sr-substituted hydroxyapatite (HA). The main objectives of the current work are to understand the bio-degradation mechanism of Mg-0.3Sr-0.3Ca, to identify the exact nature of its protective layer and to evaluate the in vitro and in vivo biocompatibility of the alloy for cardiovascular applications. To better simulate the physiological environment, the alloy was immersed in SBF which was daily refreshed. Raman spectroscopy and X-Ray photoelectron spectroscopy (XPS) confirmed the formation of a thin, Sr-substituted HA layer at the interface between the alloy and the corrosion products. In vitro biocompatibility evaluated via indirect cytotoxicity assays using HUVECs showed no toxicity effect and ions extracted from Mg-0.3Sr-0.3Ca in fact increased the viability of HUVECs after one week. In vivo tests were performed by implanting a tubular Mg-0.3Sr-0.3Ca stent along with a WE43 control stent into the right and left femoral artery of a dog. Post implantation and histological analyses showed no thrombosis in the artery with Mg-0.3Sr-0.3Ca stent after 5weeks of implantation while the artery implanted with WE43 stent was extensively occluded and thrombosed. Microscopic observation of the Mg-0.3Sr-0.3Ca implant-tissue interface confirmed the in situ formation of Sr-substituted HA on the surface during in vivo test. These results show that the interfacial layer protects the surface of the Mg-0.3Sr-0.3Ca alloy both in vitro and in vivo, and is the key factor in the bio-corrosion resistance of the alloy.


INR Control of Patients with Mechanical Heart Valve on Long-Term Warfarin Therapy.
Warfarin is an anticoagulant indicated for patients who had undergone mechanical heart valve(s) replacement (MHVR). In these patients, time in therapeutic range (TTR) is important in predicting the bleeding and thrombotic risks. This study aimed to describe the anticoagulation control of warfarin using TTR in patients with MHVR in a tertiary health care referral Center. Data were collected retrospectively by reviewing clinical notes of outpatients who attended international normalized ratio (INR) clinics in November 2015. Patients who had MHVR and who took warfarin were included. The data collected were demographics, relevant laboratory investigations, and patients' prior medical history. TTR was calculated using Rosendaal and traditional methods. A total of 103 patients with MHVR were recruited. The mean age was 51.72 ± 13.97 years and 46.6% were male. A total of 54.4% had mitral valve replacement (MVR), whereas 26.2% had aortic valve replacement (AVR). The mean TTR calculated using the Rosendaal method was 57.1%. There was no significant difference among patients with AVR, MVR, and both valves (AMVR) in terms of TTR (AVR vs. MVR vs. AMVR, 62.94 ± 23.08, 54.12 ± 21.62, 57.63 ± 17.47; p = 0.213). The average dose of warfarin for all groups was approximately 3 mg/day. Moreover, MVR, AVR, and AMVR patients who had TTR (Rosendaal method) ≤60% were 58.9%, 37.0%, and 45.0%, respectively. Only 4.8% had minor bleeding, whereas none had stroke in the period of TTR determination. Despite a majority of patients having <60% TTR, there were low incidences of bleeding and stroke events in this center. There were no factors found to be associated with INR control in this study.


Immunohistochemical Detection of Encephalitozoon cuniculi in Ocular Structures of Immunocompetent Rabbits.
Encephalitozoonosis is a common infectious disease widely spread among rabbits. Its causative agent, Encephalitozoon cuniculi, is considered as a zoonotic and emerging pathogen capable of infecting both immunocompetent and immunocompromised hosts, including humans. In rabbits, clinical signs include neurological, kidney and ocular disease. The aim of this study was to detect E. cuniculi in ocular structures in immunocompetent rabbits after experimental oral infection using immunohistochemistry. In infected animals, E. cuniculi spores were present in periocular connective tissue, sclera, cornea, choroidea, iris, retina and lens, as a round to ovoid organism reacting with a specific anti-E. cuniculi monoclonal antibody as early as 2 weeks after infection. There were no signs of inflammatory lesions in any of the ocular tissues examined at 2, 4, 6 and 8 weeks after infection. In the present study, E. cuniculi was also detected in the lenses of adult rabbits, which indicates that ways of lens infection other than intrauterine and haematogenic are possible.


Use of supercritical carbon dioxide technology for fabricating a tissue engineering scaffold for anterior cruciate ligament repair.
Tissue-engineered grafts may be useful in Anterior Cruciate Ligament (ACL) repair and provide a novel, alternative treatment to clinical complications of rupture, harvest site morbidity and biocompatibility associated with autografts, allografts and synthetic grafts. We successfully used supercritical carbon dioxide (Sc-CO2) technology for manufacturing a "smart" biomaterial scaffold, which retains the native protein conformation and tensile strength of the natural ACL but is decellularized for a decreased immunogenic response. We designed and fabricated a new scaffold exhibiting (1) high tensile strength and biomechanical properties comparable to those of the native tissue, (2) thermodynamically-stable extra-cellular matrix (ECM), (3) preserved collagen composition and crosslinking, (4) a decellularized material milieu with potential for future engineering applications and (5) proven feasibility and biocompatibility in an animal model of ligament reconstruction. Because of the "smart" material ECM, this scaffold may have the potential for providing a niche and for directing stem cell growth, differentiations and function pertinent to new tissue formation. Sc-CO2-related technology is advanced and has the capability to provide scaffolds of high strength and durability, which sustain a lifetime of wear and tear under mechanical loading in vivo.


Dual specificity phosphatase 22 relates to skin lesion degree and biologics history, while its longitudinal elevation during treatment reflects better outcome in psoriasis patients.
Dual specificity phosphatase 22 (DUSP22) plays an important role in the regulation of immune and inflammation, but its correlation with clinical features and treatment outcome in psoriasis patients is still unclear. This study was to investigate the longitudinal change of DUSP22 with time, as well as its association with disease activity and treatment response in psoriasis patients. Totally, 120 psoriasis patients, 50 patients with other skin inflammations as disease controls (DCs), and 50 health controls (HCs) were recruited. Serum samples were collected from psoriasis patients at baseline, month (M)1, M3, and M6 after initiation of etanercept-based treatment as well as from DCs and HCs after enrollment to assess DUSP22 level by enzyme-linked immunosorbent assay. DUSP22 was lower in psoriasis patients than in HCs and DCs (both p < 0.001). Besides, in psoriasis patients, DUSP22 was associated with lower psoriasis area severity index (PASI) score (p = 0.001) and systemic biological treatment history (p = 0.023), but not with other demographics, disease characteristics, or treatment history (all p>0.05). In addition, DUSP22 was increased with time (p < 0.001) in total patients. Moreover, DUSP22 at M3 (p = 0.004) and M6 (p < 0.001) was higher in response patients than in non-response patients evaluated by PASI 75. Additionally, DUSP22 at M3 (p < 0.001) and M6 (p = 0.003) was also increased in response patients compared with non-response patients evaluated by PASI 90. DUSP22 decreases and negatively correlates with disease activity, while its longitudinal elevation with time reflects satisfactory treatment response in psoriasis patients.


TNFR1 signaling kinetics: spatiotemporal control of three phases of IKK activation by posttranslational modification.
TNFα is a pleotropic cytokine that plays a central role in the inflammatory response by activating the NF-κB signaling pathway, and is targeted in a range of chronic inflammatory diseases, underscoring the therapeutic importance of understanding its underlying molecular mechanisms. Although K63-linked ubiquitination of RIP1 by TRAF2/5 and cIAP1/2 was thought to serve as a scaffold to activate the NF-κB pathway, the recent accumulation of conflicting results has challenged the necessity of these proteins in NF-κB activation. In addition, several serine/threonine kinases have been implicated in TNFα-induced IKK activation; however, the targeted disruption of these kinases had no effect on transient IKK activation. The recent discovery of RIP1-dependent and -independent activation of the early and delayed phases of IKK and TRAF2 phosphorylation-dependent activation of the prolonged phase of IKK offers a reconciliatory model for the interpretation of contradictory results in the field. Notably, the TNFα-induced inflammatory response is not exclusively controlled by the NF-κB pathway but is subject to regulatory crosstalk between NF-κB and other context-dependent pathways. Thus further elucidation of these spatiotemporally-coordinated signaling mechanisms has the potential to provide novel molecular targets and therapeutic strategies for NF-κB intervention.


Glomerular filtration in the isolated perfused kidney. I. Sieving of macromolecules.
The permeability of the glomerular capillary wall to neutral macromolecules was studied in isolated perfused rat kidneys. Pluronic F108 (BASF, Wyandotte, MI, USA), a polyoxyethylene-polyoxypropylene block copolymer of mol weight approximately 14,000, was used as plasma expander. Pore theory was applied to the fractional clearances of Pluronic F108 and dextran (mol weight 19,400) molecules measured both as a function of glomerular filtration rate. Using the pore model of Verniory et al. [30] the effective pore radius (60.9 A) and the ratio of total pore area and pore length (4.0 cm/nephron) were estimated, and a hydraulic permeability coefficient KF (0.036 nl/s . mm Hg) was calculated. There was no significant difference between the fractional clearance of Pluronic F108 obtained with different Pluronic F108 concentrations over the range 15-35 g/l, hence with largely differing osmotic pressures. It was concluded that the sieving properties of the glomerular membrane of the isolated perfused rat kidney are not detectably different from those in the intact rat, at least in the case of uncharged macromolecules.


Respiratory medication adherence in chronic lung disease of prematurity.
Chronic lung disease of prematurity (CLDP) is a frequent complication of premature birth. Infants and children with CLDP are often prescribed complex medication regimens, which can be difficult for families to manage. We sought to determine whether non-adherence was associated with increased CLDP-related morbidities and to identify predictors of adherence. Recruited caregivers of 194 children with CLDP completed questionnaires regarding self-reported adherence, respiratory outcomes, and quality of life (January 2008-June 2010). Adherence data were available for 176 subjects, of whom 143 had self-reported data only, and 33 had prescription claims data, which were used to calculate a medication possession ratio (MPR). Participants in the Prescription Claims Sample (n = 33) were more likely to have public insurance (P < 0.001). Self-reported adherence substantially overestimated medication possession; the mean MPR was 38.8% (n = 33) and was not associated with self-reported adherence (P = 0.71; n = 26). In a small sample, higher MPR was associated with decreased odds ratios of visiting the emergency department (ED) (OR = 0.75 for a 10% increase in MPR [95%CI: 0.58, 0.97]; P = 0.03; n = 74 questionnaires from 28 participants), activity limitations (OR = 0.71 [95%CI: 0.53, 0.95]; P = 0.02; n = 70 questionnaires from 28 participants), and rescue medication use (OR = 0.84 [95%CI: 0.73-0.98]; P = 0.03; n = 70 questionnaires from 28 participants). Increasing caregiver worries regarding medication efficacy and side effects were associated with lower MPR (P = 0.04 and 0.02, respectively; n = 62 questionnaires from 27 participants). Socio-demographic and clinical risk factors were not predictors of MPR (n = 33). We found that non-adherence with respiratory medications was common in premature infants and children with CLDP. Using multiple timepoints in a small sample, non-adherence was associated with a higher likelihood of respiratory morbidities. Although self-reported adherence and demographic characteristics did not predict MPR, concerns about medications did. We suggest that addressing caregiver concerns about medications may improve adherence and ultimately decrease CLDP-related morbidities. Larger, prospective studies are needed to confirm these findings and determine which factors predict non-adherence.


Systematic Review of All-Arthroscopic Versus Mini-Open Repair of Rotator Cuff Tears: A Meta-Analysis.
The objective of this study was to compare outcomes in patients with rotator cuff tears undergoing all-arthroscopic versus mini-open rotator cuff repair. A systematic review and meta-analysis of outcomes of all-arthroscopic repair versus mini-open repair in patients with rotator cuff repair was conducted. Studies meeting the inclusion criteria were screened and included from systematic literature search for electronic databases including Medline, Embase, Cochrane CENTRAL, and CINAHL library was conducted from 1969 and 2015. A total of 18 comparative studies including 4 randomized clinical trials (RCTs) were included. Pooled results indicate that there was no difference in the functional outcomes, range of motion, visual analog scale (VAS) score, and short-form 36 (SF-36) subscales. However, Constant-Murley functional score was found to be significantly better in patients with mini-open repair. However, the results of the review should be interpreted with caution due to small size and small number of studies contributing to analysis in some of the outcomes. All-arthroscopic and mini-open repair surgical techniques for the management of rotator cuff repair are associated with similar outcomes and can be used interchangeably based on the patient and rotator tear characteristics.


An unusual case of severe left ventricle outflow tract obstruction due to a coexistence of Takotsubo cardiomyopathy with septal hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is a genetic disorder presenting with a pathological increase of left ventricle (LV) wall thicknesses. The most frequent morphological form is characterized by an abnormal LV basal septal hypertrophy. Tako-Tsubo cardiomyopathy (TTC) is a transient left ventricular systolic dysfunction induced by high physical or emotional stress. Its occurrence with HCM is unusual. However, this presentation occurs more often with the classic asymmetrical septal hypertrophy compared with the apical variant. This case demonstrates that the coexistence of TTC with septal HCM in an elderly patient may lead to a severe hemodinamic instability picture.


The dorsal subiculum mediates the acquisition of conditioned reinstatement of cocaine-seeking.
Contextual stimuli present during a single lifetime cocaine self-administration experience acquire occasion-setting actions sufficient to persistently elicit cocaine-seeking behavior in rats, with effects lasting nearly 1 year. The goal of this study was to identify neural substrates mediating the acquisition of drug-related conditioning taking place during a single cocaine self-administration experience with focus on the subicular formation, a brain site that has been implicated in associative learning relevant for conditioned reward-seeking including conditioned reinstatement. Male Wistar rats were given 2 h of response-contingent access to intravenous cocaine or saline in the presence of distinct stimuli that served as contextual stimuli associated with the availability and subjective effects of cocaine (S(+)) vs saline (S(-)). Before onset of the sessions, rats received bilateral microinjections of tetrodotoxin (TTX) into the ventral subiculum (VSUB) or dorsal subiculum (DSUB). Following extinction of responding by withholding cocaine, rats were subjected to reinstatement tests in which exposure to the cocaine- (but not saline) associated stimulus produced strong recovery of responding. This effect was completely abolished in rats with transient TTX inactivation of the DSUB during the conditioning session. TTX inactivation of the VSUB during conditioning did not alter the response-reinstating effects of the cocaine cue. The results suggest that functional integrity of the DSUB, but not VSUB, is critical for the acquisition of conditioned cocaine-seeking controlled by contextual stimuli under conditions where such learning occurs during a single conditioning trial.


The lived experience of serenity: using Parse's research method.
Parse's research method was used to investigate the meaning of serenity for survivors of a life-threatening illness or traumatic event. Ten survivors of cancer told their stories of the meaning of serenity as they had lived it in their lives. Descriptions were aided by photographs chosen by each participant to represent the meaning of serenity for them. The structure of serenity was generated through the extraction-synthesis process. Four main concepts--steering-yielding with the flow, savoring remembered visions of engaging surroundings, abiding with aloneness-togetherness, and attesting to a loving presence--emerged and led to a theoretical structure of serenity from the human becoming perspective. Findings confirm serenity as a multidimensional process.


[Arguments against pressure-lowering treatment of ocular hypertension. Prophylactic treatment is unnecessary].
The main argument against a pressure-lowering treatment for patients with ocular hypertension (OHT) is the principle of "first do no harm". The imprecision of intraocular pressure (IOP) measurements and the fact that increased IOP is only a risk factor for glaucoma raise major doubts on a clinical definition of OHT. The use of IOP-lowering treatment in the absence of functional or morphological glaucomatous changes should only be initiated if the IOP is very high (>32 mmHg). If the IOP is between 21 and 32 mmHg the glaucoma conversion risk of the individual patient should be estimated. The risk factors as proven in major prospective trials (OHTS/EGPS) should be assessed using the risk calculator. Only patients with a high risk (>13%) of conversion profit from prophylactic IOP-lowering treatment. For all patients with intermediate or low risk of conversion the potential side-effects (local and systemic) of the treatment outweigh the possible benefit, so that the principle of "watchful waiting" is the best for patients with OHT. If morphological or functional progression is observed IOP-lowering treatment should be started immediately.


Development of a regional food composition table for West Africa.
Knowledge of the nutrient content of foods is fundamental for virtually all nutrition-related projects, programmes and policies. Low quality compositional data may lead to inappropriate policies and funds spent unnecessarily. Existing food composition tables (FCT) for most West African countries date back to 1960 and 1970 and contain in general few foods and components without documentation. As a result of the recommendations by the Economic Community of West African States (ECOWAS) Nutrition forum and other high level meetings, FAO/INFOODS, WAHO/ECOWAS and Bioversity International developed the West African FCT. It contains 472 foods and 28 components. Emphasis was given to include data on food biodiversity by incorporating cultivars/varieties and underutilized foods. The West African FCT enables users to address diet-related health problems, strengthen local development, enhance trade and promote biodiversity. In addition it contributes to poverty alleviation in both rural and urban areas. The FCT needs to be updated regularly and it is the most recent example of INFOODS for regional food composition activities.


Rapid detection of Salmonella enterica in raw milk samples using Stn gene-based biosensor.
In this study, a DNA-based nanosensor using specific NH2 labeled single standard probe was developed against stn gene of Salmonella enterica in milk samples. The single-stranded DNA probe was immobilized on carboxylated multiwalled carbon nanotube and gold nanoparticle (c-MWCNT/AuNP) electrode using 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC): N-hydroxy succinimide-based cross-linking chemistry. Electrochemical characterization was performed using cyclic voltammetry (CV) and Differential Pulse Voltammetry (DPV) techniques. The electrode surface at each step of fabrication was characterized using scanning electron microscopy. The sensitivity and lower limit of detection were found to be 728.42 (μA/cm2)/ng and 1.8 pg/6 μl (0.3 pg/ml), respectively, with regression coefficient (R 2) of 0.843 using DPV. The sensor was further validated using raw and artificial milk samples, and results were compared with conventional methods of detection. The developed sensor was found to be highly sensitive and stable up to 6 months, with only 10% loss of initial peak current in CV analysis on storage at 4 °C.


Knowledge and attitudes about burn complications in medical students.
Burn injury in developing countries is a major cause of morbidity and mortality. Pakistan faces a widespread problem of burn complications. The objective of this cross sectional study was to assess knowledge and attitudes in medical students regarding burn complications. A 12-question survey was distributed among 3rd, 4th and 5th year students of public sector medical colleges of Karachi, Pakistan. Out of 353 respondents, the proportion of students that were aware of burn complications was the following, with an expected response of 100% for each complication: depression [86%], fear [53.3%], post-traumatic stress disorder [40.8%], suicidal tendencies [35.1%], sleep disorder [30%], anxiety [27%], guilt [12.7%], personality changes [7%], eating disorder [5.4%], cardiac arrest [68%], hypothermia [64.3%], contractures [61%], infection [43.6%], chronic pain [41.6%], scarring [33%], chronic inflammation [24.9%], and muscle wasting [22.9%]. Most students were of the view that scarring occurs in third-degree burns [68%] only; being unaware of its presence in second-degree burns. 19.3% of the students incorrectly thought that surgery is needed for the healing of all burn patients. There appears to be a lack of basic knowledge about the physiological and psychological complications of burns among medical students of Pakistan.


Monoclonal antibody based immunoassay: An alternative way for aquatic environmental selenium detection.
Environmental concerns about human health encouraged increasing methodological interest in selenium (Se), which is an essential non-metal trace element and varies within a narrow concentration range between essential and toxic. In this study, two types of long-armed Se haptens (Se-hapten-lc-NHS) were synthesized for the first time using active ester formalization. In producing monoclonal antibodies (mAbs), the derivatization of haptenized Se at para- (meta-) and ortho-sites showed different properties. Finally, a mAb derived from hybridoma 5A52 was confirmed to be capable of establishing an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA). There was a successful quantitative determination of Se4+ with a detection range of 17 to 207 pmol mL-1 and a limit of detection of approximately 3.9 pmol mL-1. The mAb was found to be remarkably sensitive and specific, with no evidence of cross-reactivity with other ions. The assay was validated for four kinds of Se forms in water samples and showed satisfactory recoveries between 80 % and 108 %, with coefficients of variation of 2.1 %-11 %. The method proposed in our study offers a useful protocol for the rapid screening of Se and provides an alternative solution for the analysis of Se in aquatic environments.


Within-day bidirectional associations between physical activity and affect: A real-time ambulatory study in persons with and without depressive and anxiety disorders.
Ambulatory assessments offer opportunities to study physical activity level (PAL) and affect at the group and person-level. We examined bidirectional associations between PAL and affect in a 3-h timeframe and evaluated whether associations differ between people with and without current or remitted depression/anxiety. Two-week ecological momentary assessment (EMA) and actigraphy data of 359 participants with current (n = 93), remitted (n = 176), or no (n = 90) Composite International Diagnostic Interview depression/anxiety diagnoses were obtained from the Netherlands Study of Depression and Anxiety. Positive affect (PA) and negative affect (NA) were assessed by EMA 5 times per day. Average PAL between EMA assessments were calculated from actigraphy data. At the group-level, higher PAL was associated with subsequent higher PA (b = 0.109, p < .001) and lower NA (b = -0.043, p < .001), while higher PA (b = 0.066, p < .001) and lower NA (b = -0.053, p < .001) were associated with subsequent higher PAL. The association between higher PAL and subsequent lower NA was stronger for current depression/anxiety patients than controls (p = .01). At the person-level, analyses revealed heterogeneity in bidirectional associations. Higher PAL may improve affect, especially among depression/anxiety patients. As the relationships vary at the person-level, ambulatory assessments may help identify who would benefit from behavioral interventions.


Interactive dressings and topical agents.
Wound healing is a complex process that often becomes problematic in complicated patients. When abnormal wound healing occurs, there are many possible ways to intervene. One intervention is through the use of dressings and topical agents. This article is a review of the latest dressings and topical agents available in the United States. Recommendations for use are made based on the most current data in the medical literature.


IgG4-related tubulointerstitial nephritis presenting with psychiatric manifestations and skin lesions.
We describe a 21-year male with mood disorder on lithium therapy and psoriasis-like skin lesions presenting with rapidly progressive renal failure. The kidney biopsy showed acute tubulointerstitial nephritis with immunoglobulin G4-positive plasma cell infiltration. He was started on oral steroids with a provisional diagnosis of IgG4-related tubulointerstitial nephritis. All dermatological, psychiatric and renal manifestations dramatically improved, and he was taken off lithium. He had a relapse of his psychiatric symptoms on stopping steroids, and they again responded to steroids.


Unusual clinical presentation of spinal echinococcal cyst imitating a malignant tumour.
Spinal echinococcal cyst is very uncommon and may have variable clinical presentations. We describe an exceptional case of intradural and extramedullary spinal echinococcal cyst, misguided as a spinal tumour on radiological examination and was diagnosed as echinococcal cyst on fine needle aspiration biopsy smears and subsequently on histopathological examination.


Data processing and analysis in the Multicenter Morphometric Mammary Carcinoma Project (MMMCP).
In the Multicenter Morphometric Mammary Carcinoma Project (MMMCP), the prognostic value and reproducibility of routinely assessed quantitative pathological parameters in breast cancer is prospectively studied in approximately 3000 patients. Considering the high number of patients and the fact that many laboratories and hospitals throughout the Netherlands participate in this project, data acquisition, processing and analysis is an important component of the project. The data collection scheme, the structure of the database and the processing of data are described.


Estimation of salivary and serum basic fibroblast growth factor in treated and untreated patients with oral squamous cell carcinoma.
The purpose of this study was to evaluate salivary and serum basic fibroblast growth factor (bFGF) level in OSCC patients to provide a reliable biomarker for the early detection, monitoring, and prognosis of OSCC patients. The study enrolled 90 subjects, equally grouped as recently diagnosed & untreated OSCC patients (Group I), treated OSCC without any recurrence (Group II) & as control (Group III). Enzyme-linked immunosorbent assay was employed to measure bFGF concentrations in saliva and serum samples of all three groups. The results were tabulated and analyzed statistically. Group I showed high-level of bFGF expression profile in saliva (8.80 ± 1.26 pg/ml) whereas the levels of bFGF in group II (2.69 ± 0.17 pg/ml) and Group III (3.17 ± 0.43 pg/ml) are significantly lower than group I. Serum bFGF levels were also high in group I (6.33 ± 0.81 pg/ml) and decreased significantly in group II (3.52 ± 0.45 pg/ml) however, the control group showed elevated range of levels (7.63 ± 0.88 pg/ml). This study demonstrates the reliability of salivary bFGF marker as diagnostic as well as prognostic marker. Serum bFGF could also be used as prognostic marker only in Oral Squamous cell carcinoma patients.


Impact of forest disturbance on the pollen influx in lake sediments during the last century.
The pollen accumulation rates of four lakes in different regions of Estonia were estimated in order to study the relationship between pollen influx and the character and intensity of disturbances in the pollen catchment area. The pollen influx data obtained are in accordance with model calculations on the size of the pollen source areas. The influx of arboreal pollen and that of the dominant taxa (mainly Pinus) in the lakes investigated shows that, in the case of small lakes (area 3-6ha) in a forested landscapes, the bulk of the pollen originates from an area within 100-200m around the lake. The distribution patterns of influx from two lakes situated close to each other but at different distances from forest fires show that past disturbances can be reliably detected when the disturbance occurred in the immediate vicinity of the lake and at least 25% of the local pollen source area was involved. In the case of a large lake (137ha) only fires embracing thousands of hectares can be detected in the pollen diagrams.


Nicotinamide phosphoribosyltransferase as a biomarker for the diagnosis of infectious pleural effusions.
Nicotinamide phosphoribosyltransferase (NAMPT) has been reported to be involved in infectious diseases, but it is unknown whether it plays a role in infectious pleural effusions (IPEs). We observed the levels of NAMPT in pleural effusions of different etiologies and investigated the clinical value of NAMPT in the differential diagnosis of infectious pleural effusions. A total of 111 patients with pleural effusion were enrolled in the study, including 25 parapneumonic effusions (PPEs) (17 uncomplicated PPEs, 3 complicated PPEs, and 5 empyemas), 30 tuberculous pleural effusions (TPEs), 36 malignant pleural effusions (MPEs), and 20 transudative effusions. Pleural fluid NAMPT levels were highest in the patients with empyemas [575.4 (457.7, 649.3) ng/ml], followed by those with complicated PPEs [113.5 (103.5, 155.29) ng/ml], uncomplicated PPEs [24.9 (20.2, 46.7) ng/ml] and TPEs [88 (19.4, 182.6) ng/ml], and lower in patients with MPEs [11.5 (6.5, 18.4) ng/ml] and transudative effusions [4.3 (2.6, 5.1) ng/ml]. Pleural fluid NAMPT levels were significantly higher in PPEs (P < 0.001) or TPEs (P < 0.001) than in MPEs. Moreover, Pleural fluid NAMPT levels were positively correlated with the neutrophil percentage and lactate dehydrogenase (LDH) levels and inversely correlated with glucose levels in both PPEs and TPEs, indicating that NAMPT was implicated in the neutrophil-associated inflammatory response in infectious pleural effusion. Further, multivariate logistic regression analysis showed pleural fluid NAMPT was a significant predictor distinguishing PPEs from MPEs [odds ratio (OR) 1.180, 95% confidence interval (CI) 1.052-1.324, P = 0.005]. Receiver-operating characteristic (ROC) analysis demonstrated that NAMPT was a promising diagnostic factor for the diagnosis of infectious effusions, with the areas under the curve for pleural fluid NAMPT distinguishing PPEs from MPEs, TPEs from MPEs, and IPEs (PPEs and TPEs) from NIPEs were 0.92, 0.85, and 0.88, respectively. In conclusion, pleural fluid NAMPT could be used as a biomarker for the diagnosis of infectious pleural effusions.


Magnolol inhibits colonic motility through down-regulation of voltage-sensitive L-type Ca2+ channels of colonic smooth muscle cells in rats.
This study aimed to investigate the effect of magnolol (5,5'-diallyl-2,2'-biphenyldiol) on contraction in distal colonic segments of rats and the underlying mechanisms. Colonic segments were mounted in organ baths for isometric force measurement. Whole-cell voltage-sensitive L-type Ca(2+) currents were recorded on isolated single colonic smooth muscle cells using patch-clamp technique. The spontaneous contractions and acetylcholine (ACh)- and Bay K 8644-induced contractions were inhibited by magnolol (3-100 μM). In the presence of Bay K8644 (100 nM), magnolol (10-100 μM) inhibited the contraction induced by 10 μM ACh. By contrast, tetrodotoxin (100 nM) and Nώ-nitro-L-arginine methyl ester (L-NAME 100 μM) did not change the inhibitory effect of magnolol (10 μM). In addition, magnolol (3-100 μM) inhibited the L-type Ca(2+) currents. The present results suggest that magnolol inhibits colonic smooth muscle contraction through downregulating L-type Ca(2+) channel activity.


A new device for impression transfer for non-parallel endosseus implants.
The three-dimensional orientation of dental implant is transferred to a model by means of transfer device and impression material. If more than one implant is inserted and fixtures are not perfectly parallel, the impression may become distorted when removed from the mouth. In this case, a transfer that can be disengaged from the internal implant-abutment connection and removed together with the tray could be useful. An impression transfer device composed of a proper transfer, an inner hexagon and a central screw is described. When the central screw and the hexagon are removed, the proper transfer is free to move horizontally and the tray can be removed from the mouth without distortion of the impression material.


Aging skin and food supplements: the myth and the truth.
The frenzied rhythm of our times leads our patients not only to resource to diet integrators-remorselessly overcoming difficulties or prejudices-to fulfill increasingly frequent nutritional needs due to decreasingly "correct" eating habits, but also to fight against a myriad of skin conditions. The rationale of a combined approach for the antiaging treatment of skin is based on the synergic effect between functional substances applied locally, where the problem arises, and other agents working from the inside to correct a need, to restore altered functions or conditions and to guarantee the correct intake of nutrients or active substances. This work discusses the active ingredients mostly used in the oral treatment of skin aging, together with the scientific evidences that do or do not support their use.