Changes in salivary matrix metalloproteinase-3, -8, and -9 concentrations after 6 weeks of non-surgical periodontal therapy.
Studies using salivary inflammatory biomarkers for diagnosing and monitoring the progression of periodontal disease have garnered increased attention in recent years. The present study aimed to identify changes in clinical parameters and concentrations of salivary matrix metalloproteinases (MMPs) following 6 weeks of non-surgical periodontal therapy (NSPT). A 6-week NSPT program was applied to 51 adults aged ≥ 20 years. The program involved scaling, root planing, and professional toothbrushing for healthy participants and those with periodontal disease. Patients with periodontal disease underwent professional toothbrushing during all three visits. Periodontal pocket depth (PD) and gingival bleeding were assessed at week 0, week 3, and week 6, and saliva samples were collected to measure the concentrations of MMP-3, -8, and -9. All clinical parameters were improved in the periodontal disease groups following the NSPT course. Compared with healthy participants, the patients with periodontal disease showed increased concentrations of salivary MMP-3, -8, and -9. During the 6-week program, patients with periodontal disease also showed significant reductions in PD and gingival bleeding during the third week; no significant reduction was found during the sixth week. Significant reductions in the concentrations of salivary MMP-3, -8, and -9 were also noted in the periodontal disease group at week 3. The sensitivity and specificity of MMP-3 for predicting periodontitis were 81.8% and 55.5%, respectively. The present study found that NSPT resulted in reductions of salivary MMP-3, -8, and -9, and identified the potential of MMP-3 as a biomarker in the diagnosis of periodontal disease. These findings may serve as foundational data for future studies into the development of diagnostic kits for periodontal disease.


[Effect adrenaline and ephedrine against a background of aminazine on systemic, cerebral and extracerebral hemodynamics].
Experiments with anesthetized cats demonstrated chlorpromazine (2 mg/kg) to pervert the vasopressor action of adrenaline (5 mkg/kg) and ephedrine (2 mg/kg) on the systemic arterial pressure, cerebral and extracerebral tonicity of the vessels. The authors believe that with chlorpromazine pretreatment the adrenomimetics produce a selective stimulation of the beta-adrenergic receptors, this accounting for the observed depressor effect.


2[125I]iodomelatonin binding sites in spleens of guinea pigs.
2-[125I]Iodomelatonin was found to bind specifically to the membrane preparations of the spleens of guinea pigs with high affinity. The binding was rapid, stable, saturable and reversible. Scatchard analysis of the binding assays revealed an equilibrium dissociation constant (Kd) of 49.8 +/- 4.12 pmol/l and binding site density (Bmax) of 0.69 +/- 0.082 fmol/mg protein at mid-light (n = 10). There was no significant change in the Kd (41.8 +/- 3.16 pmol/l) or the Bmax (0.58 +/- 0.070 fmol/mg protein) at mid-dark (n = 10). Kinetic analysis showed a Kd of 23.13 +/- 4.81 pmol/l (mean +/- SE, n = 4), in agreement to that derived from the saturation studies. The 2-[125I]iodomelatonin binding sites have the following order of potency: 2-iodomelatonin greater than melatonin greater than 6-chloromelatonin much greater than N-acetylserotonin, 6-hydroxymelatonin greater than 5-methoxytryptamine, 5 methoxytryptophol greater than serotonin, 5-methoxyindole-3-acetic acid greater than 5-hydroxytryptophol, 3-acetylindole, 1-acetylindole-3-carboxyaldehyde, L-tryptophan greater than tryptamine, 5-hydroxyindole-3-acetic acid. Differential centrifugation studies showed that the binding sites are localized mainly in the nuclear fraction (65.5%), the rest are distributed in the microsomal fraction (17.4%), mitochondrial fraction (14.7%) and cytosolic fraction (0.3%). The demonstration of 2-[125I]iodomelatonin binding sites in the spleen suggests the presence of melatonin receptors and a direct mechanism of action of melatonin on the immune system.


Hyperpolarized 3He apparent diffusion coefficient MRI of the lung: reproducibility and volume dependency in healthy volunteers and patients with emphysema.
To measure the apparent diffusion coefficient (ADC) of hyperpolarized (HP) (3)He gas using diffusion weighted MRI in healthy volunteers and patients with emphysema and examine the reproducibility and volume dependency. A total of eight healthy volunteers and 16 patients with emphysema were examined after inhalation of HP (3)He gas mixed with nitrogen (N(2)) during breathhold starting from functional residual capacity (FRC) in supine position. Coronal diffusion-sensitized MR images were acquired. Each subject was imaged on three separate days over a seven-day period and received two different volumes (6% and 15% of total lung capacity [TLC]) of HP (3)He each day. ADC maps and histograms were calculated. The mean and standard deviation (SD) of the ADC at different days and volumes were compared. The reproducibility of the mean ADC and SD over several days was good in both healthy volunteers and patients (SD range of 0.003-0.013 cm(2)/second and 0.001-0.009 cm(2)/second at 6% and 15% of TLC for healthy volunteers, and a SD range of 0.001-0.041 cm(2)/second and 0.001-0.011 cm(2)/second, respectively, for patients). A minor but significant increase in mean ADC with increased inhaled gas volume was observed in both groups. Mean ADC and SD of HP (3)He MRI is reproducible and discriminates well between healthy controls and patients with emphysema at the higher gas volume. This method is robust and may be useful to gain new insights into the pathophysiology and course of emphysema.


Interpolation of solid/liquid partition coefficients, K(d), for iodine in soils.
The measurement of K(d) is difficult for most radionuclides: a different value is expected for every different soil. This study explored a modification of the constituent-K(d) approach used to estimate K(d) in geological materials. Here we selected five soils of very different compositions, four were field soils and one was an artificial potting soil. The soils were blended together in ratios of 1:1, 1:3 and 1:1:2 for all possible (60) 2- and 3-soil combinations. The K(d) was measured for each soil and each of the combined soils using additions of stable iodine. Our hypothesis was that the weighted average of the K(d)s of the original, unblended soils, weighted by the blending ratios, would be a reasonable estimate of the measured K(d)s of the blended soils. The ratios of expected/measured K(d) values did not deviate significantly from unity (a geometric mean of 0.91) for the four field soils. This result suggests that K(d) in the combined field soils could be estimated by the weighted average K(d) for the constituent soils. The resulting variation is consistent with other estimation methods. The practical implication of this finding is that, with K(d) data for a few benchmark soils in a region, one could estimate K(d) for other soils. The potting soil did not conform, and there are several possible explanations for this.


Experimental investigation of fluid drop spreading on heterogeneous and anisotropic porous media.
Study of spreading phenomena on porous substrates is important from theoretical as well as applications point of view. An example of such applications is composite processing, where operations involve displacement of air/volatiles by polymeric fluids through porous media composed of fibers. In this work, dynamics of drop spreading was investigated on fibrous porous substrates used in composite processing. These porous media are heterogeneous and anisotropic. Spreading front of silicon oil drops was tracked on borosilicate glass, quartz, and two different kinds of glass fiber mats: woven fabric and unidirectional. For the woven fabric, spreading front was observed to progress in steps of increasing and decreasing rate. For the unidirectional mat, the spreading front progressed with decreasing rate. The dynamics of spreading were fitted to power law in order to compare results with other porous substrates.


The use of DNA barcode for identifying species of Oxysarcodexia Townsend (Diptera: Sarcophagidae): A preliminary survey.
Oxysarcodexia is one of the Neotropical richest genera within the Sarcophagidae family. Medical, veterinary and forensic importance of these flies are due to their association with corpses, cases of myiasis in humans and domestic animals, and being pathogen carriers. Regarding morphological identification, molecular techniques, especially the DNA-based ones, arise as useful alternatives or complementary methodologies for species identification. Thus, in this study we aimed to investigate the potential of the COI marker (barcode region) to delimit Oxysarcodexia species in comparison with the morphological identification criteria. A COI fragment was amplified and the length of the sequences after alignment were of 648bp (149 parsimoniously informative variable sites). According to the Neighbor-Joining phylogenetic tree, specimens of the same morphological species were clustered in monophyletic clades (82-100% bootstrap branch support). Species-level resolution thus achieved was successful, despite low interspecific divergence (1.8-2.3%) and since interspecific variation was higher than intraspecific divergence (0.1-1.2%). Therefore, the use of COI barcode sequences supports differentiation and identification of the Oxysarcodexia species studied.


Self-efficacy for coping with cancer and quality of life in advanced gastric cancer patients.
Coping is one of the most frequently addressed topics in palliative care. Beliefs and expectations about one's own capacity to cope with cancer will lead to actual coping, which is known to contribute to quality of life (QoL). The current study aimed to describe self-efficacy (SE) for coping with cancer and to evaluate its relationship with QoL in advanced gastric cancer (AGC) patients. A descriptive correlational study was conducted with 202 AGC patients. SE for coping with cancer was measured by the Cancer Behavior Inventory version 3.0 - Korean. QoL was evaluated using the Functional Assessment of Cancer Therapy - Gastric (FACT-Ga) and the Functional Assessment of Chronic Illness Therapy - Spiritual Well-Being (FACIT-Sp) Korean version. Data were analyzed using t-tests, Spearman correlations and multiple regression analyses. SE for seeking and understanding medical information was the highest ranked subscale, while using spiritual coping was the lowest ranked subscale. SE for maintaining activity and independence, accepting cancer/maintaining a positive attitude/making decisions demonstrated a significant contribution to QoL as measured by the FACT-Ga and the FACIT-Sp. SE for using spiritual coping demonstrated a significant contribution to the FACIT-Sp. SE for coping with cancer demonstrated significant contributions to QoL in AGC patients. The assessment of SE for coping with cancer is recommended for practice. Considering its contribution to patients' QoL, interventions to improve SE for coping with cancer need to be pursued in future studies.


Blood lead levels and bone turnover with weight reduction in women.
High bone turnover states are known to raise blood lead levels (BPb). Caloric restriction will increase bone turnover, yet it remains unknown if weight reduction increases BPb due to mobilization of skeletal stores. We measured whole blood Pb levels ((206)Pb) by inductively coupled plasma mass spectrometry in 73 women (age 24-75 years; BMI 23- 61 kg/m(2)) before and after 6 months of severe weight loss (S-WL), moderate weight loss (M-WL), or weight maintenance (WM). Baseline BPb levels were relatively low at 0.2-6.0 microg/dl, and directly associated with age (r=0.49, P<0.0001). After severe WL (-37.4+/-9.3 kg, n=17), BPb increased by 2.1+/-3.9 microg/dl (P<0.05), resulting in BPb levels of 1.3-12.5 microg/dl. M-WL (-5.6+/-2.7 kg, n=39) and WM (0.3+/-1.3 kg, n=17) did not result in an increase in BPb levels (0.5+/-3.2 and 0.0+/-0.7 microg/dl, M-WL and WM, respectively). BPb levels increased more with greater WL (r=0.24, P<0.05). Bone turnover markers increased only with severe WL and were directly correlated with WL. At baseline, higher calcium intake was associated with lower BPb (r=-0.273, P<0.02), however, this association was no longer present after 6 months. Severe weight reduction in obese women increases skeletal bone mobilization and BPb, but values remain well below levels defined as Pb overexposure.


Effects of mating rates on oviposition, sex ratio and longevity in a predatory mite Neoseiulus cucumeris (Acari: Phytoseiidae).
Two aspects of mating effects on the fecundity, sex ratio and longevity of Neoseiulus cucumeris (Acari: Phytoseiidae) were examined in laboratory experiments: (1) females mated by one, two or three different males (unmated and 3 days old) at 5-day intervals, and (2) females mated by males with different age/mating status (number of females mated previously by the male). Females allowed to mate with a second or third male at 5-day intervals produced 39 eggs on average, but those mated with a single male produced 28 eggs on average. Matings with additional males 5 or 10 days after the first male increased the duration of the oviposition period of these females by 5-7 days and at the same time reduced the post-oviposition period by about 10 days. Overall, females with additional matings by one or two different males at 5-day intervals survived a few days shorter than females without additional males. Mating with a different female each day, a male of N. cucumeris could mate with 5-8 females, which produced a total of 85-116 eggs: females mated with a male during days 1 and 2 in its adulthood and with a male of the last 2 days of life (days 7 and 8) produced about half as many eggs as females mated with a male during 3-6 days of its adulthood. Females mated with males that are too young or too old had a shorter oviposition period and a longer post-oviposition period and longevity than females mated with middle-aged males. In both experiments, rates of oviposition remained similar in females with high or low fecundity. This indicates that in both cases, the increased fecundity is due to the extension of the oviposition period through additional sperm supplied by the second male and or third male (in experiment 1) or more sperm by males not too young nor too old (experiment 2).


Quadriceps maximal power and optimal shortening velocity in 335 men aged 23-88 years.
The ability to develop adequate quadriceps muscle power may be highly predictive of subsequent disability among older persons. Rate as well as quantitative (sarcopenia) and qualitative (among other slowing of muscles) contributors to that age-related power decline are poorly known. The relationship of quadriceps maximal short-term power (P(max)) and corresponding optimal shortening velocity (upsilon(opt)) with age was assessed in 335 healthy men aged 23-88 years. The P(max) and upsilon(opt) were measured on a friction loaded non-isokinetic cycle ergometer. Anthropometric dimensions were used to estimate lean thigh volume (LTVest) and quadriceps mass. The decline in P(max) across the adult life span (10.7% per decade) was greater than the usually reported decrease in maximal muscle strength. Power decreased already after the fourth decade. Both muscle mass (4.1% decline for LTVest or 3.4% for quadriceps mass per decade) and upsilon(opt) (6.6% decline per decade) contributed to the decrease in power. Age contributed to the variability in P(max) independently to the LTVest/quadriceps mass and upsilon(opt). The age-related decrease pattern of P(max) reflects both stabilization (or even increase) of anthropometric measures (LTVest or quadriceps mass) from youth to middleage and systematic decline of upsilon(opt) already from the thirties. This implicates more focus on velocity-orientated training as a means of enhancing leg power and improving functional status.


Microbiome taxonomic and functional profiles of two domestic sewage treatment systems.
Anaerobic systems for domestic sewage treatment, like septic tanks and anaerobic filters, are used in developing countries due to favorable economic and functional features. The anaerobic filter is used for the treatment of the septic tank effluent, to improve the COD removal efficiency of the system. The microbial composition and diversity of the microbiome from two wastewater treatment systems (factory and rural school) were compared through 16S rRNA gene sequencing using MiSeq 2 × 250 bp Illumina sequencing platform. Additionally, 16S rRNA data were used to predict the functional profile of the microbial communities using PICRUSt2. Results indicated that hydrogenotrophic methanogens, like Methanobacterium, were found in higher abundance in both systems compared to acetotrophic methanogens belonging to Methanosaeta genus. Also, important syntrophic microorganisms (Smithella, Syntrophus, Syntrophobacter) were found in the factory and rural school wastewater treatment systems. Microbial communities were also compared between stages (septic tank and anaerobic filter) of each wastewater treatment stage, revealing that, in the case of the rural school, both microbial communities were quite similar most likely due to hydraulic short-circuit issues. Meanwhile, in the factory, microbial communities from the septic tank and anaerobic filter were different. The school system showed lower COD removal rates (2-30%), which were probably related to a higher abundance of Firmicutes members in addition to the hydraulic short-circuit and low abundance of Chloroflexi members. On the other hand, the fiberglass factory presented higher COD removal rates (60-83%), harboring phyla reported as the core microbiome of anaerobic digesters (Bacteroidetes, Chloroflexi, and Proteobacteria phyla). The knowledge of the structure and composition of wastewater treatment systems may provide support for the improvement of the pollutant removal in anaerobic process.


Cardioverter-defibrillator lead-related thrombus treated with prolonged anticoagulation in patient with prothrombotic disorder.
Following an accidental finding of a large atrial lead-related thrombus in a 33-year-old woman with suspected prothrombotic disorder, a conservative treatment with low molecular weight heparin injections and close transthoracic and transesophageal echocardiographic monitoring was used. It led to a complete resolution of the thrombus in 4 weeks without the need for a high-risk operation in this patient.


A new osteosynthesis device for the treatment of proximal humerus fractures. Description of the technique and preliminary results.
The treatment of third proximal humerus complex fractures represents a challenge and osteosynthesis techniques are still controversial. The Authors report a new device that has been planned and used to treat this type of fracture, suitable for both young and elderly patients. The device consists of a perforated prismatic-triangular titanium cage (PTTC), available in different sizes so that it can be inserted in the bone cavity as a bridge. Thus, it supports the cephalic cap and, resting on the metaepiphyseal walls, allows greater and lesser tuberosities to be restored using osteosutures or minimal osteosynthesis devices. Furthermore, bone chips or bone substitutes can be inserted as filling in the perforated parts. From June 2005 to February 2006 we used this osteosynthesis surgical technique to treat 10 patients, 4 females and 6 males, all affected by proximal humerus complex fractures. No specific complications during and after surgery were noticed. The reported results are still to be considered as preliminary, but they are very encouraging. In all the cases the effective internal stabilisation allowed anatomical reduction of fragments, their stable fixation, reconstruction close to standard anatomy and early rehabilitation.


Thermoregulatory mechanisms in Sarcophaga.
The flesh fly, Sarcophaga, is frequently seen feeding on flowers during periods of high radiation when other flies of comparable size avoid exposure because of the dangers of overheating. Sarcophaga is able to maintain its intermittent flower visits due to a cuticle of high thermal reflectance, giving low intrinsic heating rates, and to an ability to shunt blood between thorax and abdomen according to its needs. The fly thus achieves partial thermoregulation and can keep its body temperature within the preferred range for longer periods than its potential entomophilous competitors.


Determination of alcohol compounds using corona discharge ion mobility spectrometry.
Ion mobility spectrometry (IMS) is a very fast, highly sensitive, and inexpensive technique, it permits efficient monitoring of volatile organic compounds like alcohols. In this article, positive ion mobility spectra for six alcohol organic compounds have been systematically studied for the first time using a high-resolution IMS apparatus equipped with a discharge ionization source. Utilizing protonated water cluster ions (H2O)n H+ as the reactant ions and clean air as the drift gas, alcohol organic compounds, ethanol, 1-propanol, 2-propanol, 1-butanol, 1-pentanol and 2-octanol, all exhibit product ion characteristic peaks in their respective ion mobility spectrometry, that is a result of proton transfer reactions between the alcohols and reaction ions (H2O)n H+. The mixture of these alcohols, including two isomers, has been detected, and the results showed that they could be distinguished effectively in the ion mobility spectrum. The reduced mobility values have been determined, which are in very well agreement with the traditional 63Ni-IMS experimental values. The exponential dilution method was used to calibrate the alcohol concentrations, and a detection limit available for the alcohols is in order of magnitude of a few ng/L.


[Early amnion rupture and fetal and newborn defects as an obstetrical and pathomorphological problem].
Early amnion rupture (EAR, EARS, EAROD) may be the cause of amniotic bands and sheets development, which may lead to different fetal defects--from minor finger amputation, chiloschisis or palatoschisis to major amputation, acranius, deep paroschisis or broad body covering cleavage. The aim of this report was to analyse cases of fetal malformation, which might have been caused by EARS. A retrospective analysis of 3173 autopsies performed within a span of 14 years (1989-2003). Among 744 cases of malformations 14 cases of fetuses and newborns presented developmental anomalies, which probably were the consequences of EARS. The EARS is probably more frequent than it is generally presumed, but it is very often impossible to find remnants of bands and sheets. Nevertheless, the presence of at least two typical anomalies excludes a different cause than early amnion rupture and amniotic bands.


Integration of light and plastid signals.
Light and plastid signals promote chloroplast biogenesis and are among the most potent inducers and repressors of photosynthesis-related gene expression, respectively. These signals can be likened to a 'gas and brake system' that promotes efficient chloroplast biogenesis and function. Recent findings indicate that a particular plastid signal can 'rewire' a light signaling network, converting it from an inducer into a repressor of particular photosynthesis-related genes. Therefore, a plastid signal appears to be an endogenous regulator of light signaling rather than a signal acting independently from light. This integration of light and plastid signals may allow plants to proactively manage chloroplast dysfunction when performing chloroplast biogenesis and maintenance in adverse light conditions.


Efficacy of botulinum-A for nocturnal bruxism pain and the occurrence of bruxism events: a meta-analysis and systematic review.
The purpose of this study was to explore the treatment efficacy of botulinum-A (BTX-A) in nocturnal bruxism. Five electronic databases (PubMed, Web of Science, Cochrane, Embase and Clinical Trials) were searched to identify related randomised controlled trials up to September 1, 2020. Five evaluation indices were extracted, namely, the pain at rest and at chewing (PR and PC), the number of bruxism events (NBE) and the self-assessment by patients (SA), to assess the treatment efficacy of BTX-A in bruxism. All data analyses were conducted using Review Manager (Version 5.3; The Cochrane Collaboration, London, United Kingdom). Six studies were included in this review. The sample was composed of 148 participants. Compared with the placebo group, the BTX-A group showed the significantly improved the PR index scores (MD, 1.16 cm; 95%CI, 0.65 to 1.67 cm; p < 0.00001), slightly improved the PC index scores (SMD, 0.25; 95%CI -0.14 to 0.64; p = 0.21), and the NBEs were significantly decreased in the before-injection group compared with that in the after-injection group (MD, 1.72; 95%CI, 0.60 to 2.85; p = 0.003). The results of this study suggest that BTX-A possesses significant therapeutic efficiency for the relief of pain and events of bruxism. However, whether the events of bruxism would recur or rebound after botulinum toxin injection needs more follow-up clinical evidence.


Patient-controlled analgesia: a controlled trial.
Thirty-six patients undergoing lower abdominal surgery were included in a prospective randomized controlled study to compare the effects of patient-controlled analgesia (PCA) and a standard intramuscular/intravenous treatment (conventional analgesia, CA) of postoperative pain. Morphine was used in both groups. There were no significant differences between the two analgesic regimens in respect of linear analogue pain scores, verbal pain-relief scores, amount of morphine used or side-effects. No treatment-induced alterations in vital values were experienced.


Proteomic analysis of cholera toxin adjuvant-stimulated human monocytes identifies Thrombospondin-1 and Integrin-β1 as strongly upregulated molecules involved in adjuvant activity.
Cholera Toxin (CT) as well as its related non-toxic mmCT and dmLT mutant proteins have been shown to be potent adjuvants for mucosally administered vaccines. Their adjuvant activity involves activation of cAMP/protein kinase A (PKA) signaling and inflammasome/IL-1β pathways in antigen presenting cells (APC). To get a further understanding of the signal transduction and downstream pathways activated in APCs by this group of adjuvants we have, employing quantitative proteomic analytic tools, investigated human monocytes at various time points after treatment with CT. We report the activation of three main biological pathways among upregulated proteins, peaking at 16 hours of CT treatment: cellular organization, metabolism, and immune response. Specifically, in the further analyzed immune response pathway we note a strong upregulation of thrombospondin 1 (THBS1) and integrin β1 (ITGB1) in response to CT as well as to mmCT and dmLT, mediated via cAMP/PKA and NFKB signaling. Importantly, inhibition in vitro of THSB1 and ITGB1 in monocytes or primary dendritic cells using siRNA abrogated the ability of the treated APCs to promote an adjuvant-stimulated Th17 cell response when co-cultured with peripheral blood lymphocytes indicating the involvement of these molecules in the adjuvant action on APCs by CT, mmCT and dmLT.


Unraveling the effect of gender dimensions and wood fuel usage on household food security: evidence from Ghana.
Food security discussions have heightened particularly with Sustainable Development Goal (SDG) 2 which focuses on hunger and malnutrition. This study investigates gender dimensions of food security and examines the role of wood fuel on households' food security in Ghana. Data from the most recent round of the Ghana Living Standards Survey (GLSS VII, 2016/2017) were used for this investigation. By employing the Exogeneous Switching Treatment Effect Regression to analyze food security, it was found that significant heterogeneities exist among different gender groups. The largest differences exist between male headed households and de jure female headed households. Further, this study finds that among female headed households, there remain substantial differences in food security. Wood fuel usage, household size and residing in the northern part of the country were found to reduce food security among households while education and income increase household food security. These findings are important for enhanced policy targeting to address food insecurity.


Optical coherence tomographic pattern and focal electroretinogram in patients with retinitis pigmentosa.
The foveal function of patients with retinitis pigmentosa (RP) has been estimated by visual acuity (VA) or visual field (VF) tests. In the present study, the potential of optical coherence tomography (OCT) and focal electroretinogram (fERG) for monitoring macular function in RP patients was investigated. Cross-sectional observational study. A total of 56 eyes of 56 patients with RP underwent ophthalmic examination including VA, VF, fERG, and OCT. Patients were morphologically divided into three groups by the appearance of photoreceptor inner/outer segment junction (IS/OS) that were depicted with OCT; type 1: no IS/OS visible, type 2: IS/OS was visible but the length was < or =2 mm, and type 3: IS/OS >2 mm was confirmed. Functional results for VA and fERG were compared and analysed based on the three groups. The average VA of type 1 patients was significantly lower than that of types 2 or 3 patients (P<0.001). There were no significant VA differences detected between types 2 and 3 patients. While most of the type 1 patients (21/22) showed non-recordable fERG, 3 out of 18 type 2 patients and none of type 3 patients showed non-recordable fERG. Significant differences of the fERG amplitudes were observed among the three groups (a-wave, b-wave, and OP, P<0.001 in all three components). However, the implicit time showed no difference between type 2 and 3. Analysing the IS/OS with OCT and the amplitudes of fERG may be helpful for monitoring RP patients in addition to VA and VF.


Deep venous thrombosis and pulmonary embolism following cardiac catheterization.
We report 4 cases of deep venous thrombosis and/or pulmonary embolism after diagnostic cardiac catheterization. Two of these cases followed left heart catheterization alone.


Goal attainment and satisfaction scores for CMHC clients.
The purpose of this study was to explore the psychometric properties of goal attainment scales and client satisfaction measures. The findings revealed that goal attainment results, like other types of self-report psychotherapy outcome measures, are directly related to (a) indicators of a client's social class, and (b) the manner of treatment termination (unilateral dropout vs. mutual consent). The extent of client--therapist agreement on goal scores was relatively low thereby supporting the necessity of obtaining both perspectives in evaluating treatment outcome. Furthermore, because measures of client satisfaction were found to be sufficiently independent from goal outcome scores, it was concluded that they provide a unique source of program evaluation data. Finally, it was concluded that Goal Attainment Scaling is best considered to be a quality assurance tool for individual client/therapist dyads rather than a mechanism for the determination of the effectiveness of specific mental health programs and services.


Preliminary study of the biomechanical behavior and physical characteristics of tantalum (Ta)-coated prostheses.
Use of Ta biomaterials in medicine started in the middle of the last century. The good biocompatibility and chemical stability, and the unique physical characteristics of Ta metal have resulted in many possible developments of Ta biomaterials. In this study, histopathological observation, histomorphometric analysis, scanning electron microscope (SEM) observation, energy-dispersive X-ray spectroscopy (EDX) analysis, biomechanical testing, and examination of the coating's mechanical strength have been used to evaluate the value of clinical application of Ta-coated prostheses prepared by a plasma-spraying process. Histopathological observation has demonstrated that the periprosthetic new bone tissues tightly and stably adhere to the Ta coating after the implantation, with no signs of loosening. Early after implantation, there is no significant difference in periprosthetic bone volume and ultimate shear strength between Ta-coated and Ti-coated prostheses (P > 0.05). EDX analysis suggests that the ultimate shear stress does not damage Ta coating. Mechanical strength testing shows that the adhesive strength and Vicker's surface hardness (HV) of the Ta coating are significantly higher than those of the Ti coating (P < 0.01). Ta coating has good stability and bone biocompatibility; the extraordinary physical characteristics of Ta coating have great significance in maintaining prosthetic stability and surface porosity after implantation.


Physics-based Models for photonic thermometers.
Resistance thermometry, meticulously developed over the last century, provides a time-tested method for taking temperature measurements. However, fundamental limits to resistance-based approaches along with a desire to reduce the cost of sensor ownership, increase sensor stability and meet the growing needs of emerging economy has produced considerable interest in developing photonic temperature sensors. In this study we utilize Della-Corte-Varshni treatment for thermo-optic coefficient to derive models for temperature-wavelength relationships in silicon ring resonators and Fiber Bragg gratings. Model evaluation is carried out using a Bayesian criteria that selects models for superior out-of-sample predictive accuracy whilst minimizing model complexity. Our work presents physics-based framework for photonic thermometry reference functions, putting constraints on model complexity and parameter bounds, pointing the way towards a reference function that can be utilized for future standardization and inter-comparison of photonic thermometers.


A 2-year follow-up after rotoresection of the prostate: a prospective study.
To evaluate the success of rotoresection of the prostate for benign prostatic hyperplasia (BPH), after a follow-up of 24 months. The 24 patients who were the subject of a previous report were followed for up to 24 months; only one patient was lost to follow-up. The mean (sd) American Urologic Association-7 score decreased from 20.5 (3.8) before surgery to 1.12 (1.56) at 24 months; the mean maximum urinary flow rate increased from 8.7 (2.1) to 21.8 (8.5) mL/s, and the mean total prostate volume decreased from 36.5 (12.9) to 21 (7.9) mL. Early complications were urinary tract infection in 10 patients and mild stress urinary incontinence in 11. One patient had a urethral stricture and another had a posterior urethral stone at 6 months; both were treated successfully with good urinary flow rates thereafter. At 24 months, 23 patients had sterile urine and were continent. Thus far, rotoresection of the prostate is a safe and effective method for treating BPH. The hospital stay was short and the functional results excellent at up to 24 months.


Metachronous squamous-cell carcinoma of the colon and treatment of rectal squamous carcinoma with chemoradiotherapy.
Rectal squamous-cell carcinoma is a rare tumour with an incidence of less than 1 per 1000 cases. We report such a case treated with chemoradiotherapy. The patient developed a metastasis in the spleen and a further squamous tumour in the right colon, both of which were successfully resected. No histological evidence of recurrent rectal tumour has been found. Two years following presentation, the patient remains disease-free although symptomatic from a radiotherapy-induced stricture of the rectum.


Spherical nucleic acids-based nanoplatforms for tumor precision medicine and immunotherapy.
Precise diagnosis and treatment of tumors currently still face considerable challenges due to the development of highly degreed heterogeneity in the dynamic evolution of tumors. With the rapid development of genomics, personalized diagnosis and treatment using specific genes may be a robust strategy to break through the bottleneck of traditional tumor treatment. Nevertheless, efficient in vivo gene delivery has been frequently hampered by the inherent defects of vectors and various biological barriers. Encouragingly, spherical nucleic acids (SNAs) with good modularity and programmability are excellent candidates capable of addressing traditional gene transfer-associated issues, which enables SNAs a precision nanoplatform with great potential for diverse biomedical applications. In this regard, there have been detailed reviews of SNA in drug delivery, gene regulation, and dermatology treatment. Still, to the best of our knowledge, there is no published systematic review summarizing the use of SNAs in oncology precision medicine and immunotherapy, which are considered new guidelines for oncology treatment. To this end, we summarized the notable advances in SNAs-based precision therapy and immunotherapy for tumors following a classification standard of different types of precise spatiotemporal control on active species by SNAs. Specifically, we focus on the structural diversity and programmability of SNAs. Finally, the challenges and possible solutions were discussed in the concluding remarks. This review will promote the rational design and development of SNAs for tumor-precise medicine and immunotherapy.


Silencing of PCDH10 in hepatocellular carcinoma via de novo DNA methylation independent of HBV infection or HBX expression.
PCDH10 is a key tumor suppressive gene for nasopharyngeal, esophageal, and other carcinomas with frequent methylation. In this study, we investigated the potential epigenetic modification of the PCDH10 gene by hepatitis B virus × protein (HBx), a pivotal factor in the progression of HBV replication and potential carcinogenesis. PCDH10 expression was found to be down-regulated in 9/13 (69.2 %) of hepatocellular carcinoma (HCC) cell lines. Decreased PCDH10 expression was correlated with the methylation status of the PCDH10 promoter. Treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (Aza) was sufficient to restore PCDH10 mRNA expression by suppressing PCDH10 promoter methylation in HepG2 cells. Treatment with Trichostatin A alone had no significant effect on PCDH10 expression but enhanced the effect of Aza. PCDH10 methylation was further detected in 76 % (38 of 50) of HCC tissues compared with 40 % (20 of 50) of paired adjacent tissues, with no methylation detected in normal human liver tissues. There were significant correlations between methylation status of PCDH10 and tumor size, serum AFP levels, metastasis or TNM staging (P < 0.05). Moreover, PCDH10 promoter methylation status was not associated with HBV infection in our panel of 50 primary HCC tumors, and transfection with HBX could not alter the status of PCDH10 promoter methylation. Collectively, these observations suggested that the expression of PCDH10 was silenced in HCC via de novo DNA methylation independent of HBV infection or HBX expression, and PCDH10 might form a potentially useful therapeutic target for HCC.


Coil Embolization of Variant Hepatic Arteries During Percutaneous Arterial Port Catheter Placement for Intraarterial Chemotherapy: Analysis of Intrahepatic Perfusion Redistribution and Treatment Efficacy.
The purpose of this study was to analyze the intrahepatic perfusion redistribution after embolization of hepatic arterial variants during percutaneous arterial port catheter placement as well as to investigate the treatment efficacy of intraarterial chemotherapy in perfusion redistribution-dependent compared to redistribution-independent liver areas. This retrospective study included 62 patients (67.7% males, mean age of 56 ± 12 years). A replaced left hepatic artery was encountered in 36/62 (58.1%), a replaced right hepatic artery in 19/62 (30.6%) and a replaced left and right hepatic artery in 7/62 of patients (11.3%), respectively. Subjective perfusion analysis was performed on digital subtracted angiography and computed tomography (CT)/cone-beam computed tomography (CBCT) images evaluating the visibility of the main, segmental and subsegmental branches of the embolized variant hepatic artery, re-perfused from intrahepatic arterial anastomoses. For objective perfusion analysis ROI measurements on CT/CBCT images were taken in the redistribution-dependent and redistribution-independent liver lobe. Response analysis according to RECIST 1.1 was separately calculated for the redistribution-dependent and redistribution-independent liver lobe. Intrahepatic reperfusion of the embolized variant hepatic artery was observed immediately after embolization with visualization of the subsegmental branches in 95.2% of patients. ROI measurements on CT/CBCT images (right lobe mean 76 ± 30.2 HU, left lobe mean 74.4 ± 30.5, p-value 0.88) did not show any differences. Treatment response after intraarterial chemotherapy did not differ between the redistribution-dependent and redistribution-independent liver lobes. Embolization of hepatic arterial variants during percutaneous arterial port catheter placement results in effective intrahepatic perfusion redistribution and does not compromise treatment efficacy of intraarterial chemotherapy in the redistribution-dependent liver lobe.


Deciding What to Do: Developments in Children's Spontaneous Monitoring of Cognitive Demands.
How do children decide which tasks to take on? Understanding whether and when children begin to monitor cognitive demands to guide task selection is important as children gain increasing independence from adults in deciding which tasks to attempt themselves. In this article, we review evidence suggesting a developmental transition in children's consideration of cognitive demands when making choices about tasks: Although younger children are capable of monitoring cognitive demands to guide task selection, spontaneous monitoring of cognitive demands begins to emerge around 5-7 years. We describe frameworks for understanding when and why children begin to monitor cognitive demands, and propose additional factors that likely influence children's decisions to pursue or avoid cognitively demanding tasks.


Trends and Characteristics of New Drug Approvals in China, 2011-2021.
In the past decade, the Chinese drug regulatory system has undergone many changes. A major reform starting in 2015 has significantly reshaped the regulatory processes. It was important to assess the impact of the reform on new drug approvals in China. We analyzed the temporal trends of regulatory characteristics of the new drugs approved by the Chinese regulatory agency from 2011 to 2021, using data collected in the Pharmcube database. A total of 353 new drugs were approved, including 220 small molecule drugs, 86 biological products and 47 vaccines. The annual number of new drug approvals increased dramatically since 2017, reaching a record high of 70 in 2021. The median NDA approval time was 15.4 months in 2017-2021, the shortest in the decade, and was significantly shorter than that in the pre-reform period. The newly instituted expedited pathways such as priority review (PR) and accelerated approval for urgently needed overseas drugs (UNOD) significantly reduced new drug application (NDA) approval times compared with standard review. For imported drugs, in 2017-2021, the median time difference between the first approval in the world and the approval in China was 5 years, representing significant "drug lag". However, the proportion of the imported drugs approved in China within 3 years of its first foreign approval has increased to 24.4% in 2017-2021. The regulatory reform has produced significant, positive immediate outcomes in several metrics of drug regulatory approval. China's regulatory system will continue to evolve as there still are many areas requiring further reform and improvement.


The management of subretinal gas following attempted pneumatic retinal reattachment.
Pneumatic retinopexy is a recently described procedure for treating retinal detachments with cryotherapy and intraocular gas injection, rather than scleral buckling. Prospective studies are underway to assess its safety and efficacy. One potential complication of this technique is persistent detachment due to subretinal gas. We report seven cases of subretinal gas following attempted pneumatic retinal reattachment. In all cases, multiple fish-egg gas bubbles were present following injection; some of these bubbles gained access to the subretinal space during the early postoperative period. The subretinal gas gave the detached retina a pearly, dome-shaped, refractive sheen. Three cases were managed by positioning the patients' heads to allow the subretinal gas to pass through the retinal break back into the vitreous cavity. One case underwent successful scleral buckling that closed the retinal break despite the presence of a small subretinal gas bubble. Three cases required vitrectomy, air-fluid exchange, and cryotherapy or endolaser treatment. In five of the seven eyes the retina was eventually reattached successfully.


An integrated analytical strategy to decipher the metabolic profile of alkaloids in Compound Kushen injection based on UHPLC-ESI-QTOF/MSE.
Compound Kushen injection (CKI) is a kind of sterilised water-soluble traditional Chinese medicine preparation that has been used for the clinical treatment of a variety of cancers (hepatocellular carcinoma, lung cancer, etc.) for 19 years. However, to date, the metabolism-related study on CKI in vivo has not been conducted.An integrated analytical strategy was established to investigate the metabolic profile of alkaloids of CKI in rat plasma, urine, and faeces based on ultra-high performance liquid chromatography-electrospray quadrupole time-of-flight mass spectrometry in MSE mode (UHPLC-ESI-QTOF/MSE).Nineteen prototype alkaloids (including 12 matrine-type alkaloids, 2 cytisine-type alkaloids, 3 lupinine-type alkaloids, and 2 aloperine-type alkaloids) of CKI were identified in vivo. Furthermore, 71 metabolites of alkaloids (including 11 of lupanine-related metabolites, 14 of sophoridine-related metabolites, 14 of lamprolobine-related metabolites, and 32 of baptifoline-related metabolites) were tentatively characterised. Metabolic pathways involved in the metabolism of phase I (include oxidation, reduction, hydrolysis, and desaturation), phase II (mainly include glucuronidation, acetylcysteine or cysteine conjugation, methylation, acetylation, and sulphation), and associated combination reactions.The integrated analytical strategy was successfully used to characterise the prototype alkaloids and their metabolites of CKI in vivo, and the results laying a foundation for further study its pharmacodynamic substances.


Phosphate inhibition of secondary metabolism in Streptomyces hygroscopicus and its reversal by cyclic AMP.
Inorganic phosphate inhibited the biosynthesis of the macrolide antibiotic turimycin in different strains of Streptomyces hygroscopicus. In the wild type strain a depression was observed with increasing phosphate concentrations. A total inhibition was found at 0.1 M phosphate. In a high producing mutant a minimum of turimycin production occured when the phosphate concentration was between 5 mM and 10 mM. Above this concentration the antibiotic synthesis increased again but the production period shifted to a later period of cultivation. Addition of inorganic phosphate resulted in an initial increase of intracellular cyclic AMP content. But a second elevation characterizing the normal level of cyclic AMP throughout the growth phase was prevented by phosphate. Exogenous cyclic AMP as well as positive effectors of the adenylyl cyclase system were able to overcome the phosphate suppression. Cyclic AMP abolished the reduction of protein synthesis following phosphate addition and caused the reappearance of a protein band which may be responsible for the turimycin biosynthesis.


Cardiomyocyte-specific knockout and agonist of peroxisome proliferator-activated receptor-gamma both induce cardiac hypertrophy in mice.
Peroxisome proliferator-activated receptor (PPAR)-gamma is required for adipogenesis but is also found in the cardiovascular system, where it has been proposed to oppose inflammatory pathways and act as a growth suppressor. PPAR-gamma agonists, thiazolidinediones (TZDs), inhibit cardiomyocyte growth in vitro and in pressure overload models. Paradoxically, TZDs also induce cardiac hypertrophy in animal models. To directly determine the role of cardiomyocyte PPAR-gamma, we have developed a cardiomyocyte-specific PPAR-gamma-knockout (CM-PGKO) mouse model. CM-PGKO mice developed cardiac hypertrophy with preserved systolic cardiac function. Treatment with a TZD, rosiglitazone, induced cardiac hypertrophy in both littermate control mice and CM-PGKO mice and activated distinctly different hypertrophic pathways from CM-PGKO. CM-PGKO mice were found to have increased expression of cardiac embryonic genes (atrial natriuretic peptide and beta-myosin heavy chain) and elevated nuclear factor kappaB activity in the heart, effects not found by rosiglitazone treatment. Rosiglitazone increased cardiac phosphorylation of p38 mitogen-activated protein kinase independent of PPAR-gamma, whereas rosiglitazone induced phosphorylation of extracellular signal-related kinase 1/2 in the heart dependent of PPAR-gamma. Phosphorylation of c-Jun N-terminal kinases was not affected by rosiglitazone or CM-PGKO. Surprisingly, despite hypertrophy, Akt phosphorylation was suppressed in CM-PGKO mouse heart. These data show that cardiomyocyte PPAR-gamma suppresses cardiac growth and embryonic gene expression and inhibits nuclear factor kappaB activity in vivo. Further, rosiglitazone causes cardiac hypertrophy at least partially independent of PPAR-gamma in cardiomyocytes and through different mechanisms from CM-PGKO.


Esophageal stents for iatrogenic esophageal perforations during cardiac surgery.
The usefulness and safety of transesophageal echocardiography during cardiac surgery have been well described in the literature. However, rare complications of this procedure can occur and should be familiar to surgeons and anesthesiologists. A series of two cases of esophageal perforation by echoprobe during cardiac surgery treated successfully by endoscopic stenting are reported.


Contrast Induced Acute Kidney Injury and its Impact on Mid-Term Kidney Function, Cardiovascular Events and Mortality.
The existence and clinical relevance of contrast induced acute kidney injury (CI-AKI) is still heavily debated and angiographic procedures are often withheld in fear of CI-AKI, especially in CKD-patients. We investigated the incidence of CI-AKI in cardiovascular high risk patients undergoing intra-arterial angiography and its impact on mid-term kidney function, cardiovascular events and mortality. We conducted a prospective observational trial on patients undergoing planned intra-arterial angiographic procedures. All subjects received standardized intravenous hydration prior to contrast application. CI-AKI was defined according to a ≥25% increase of creatinine from baseline to either 24hrs or 48hrs after angiography. Plasma creatinine and eGFR were recorded from the institutional medical record system one and three months after hospital discharge. Patients were followed up for two years to investigate the long term effects of CI-AKI on cardiovascular events and mortality. We studied 706 (317 female) patients with a mean eGFR of 52.0 ± 15 ml·min-1·1.73 m-2. The incidence of CI-AKI was 10.2% (72 patients). In 94 (13.3%) patients serum creatinine decreased ≥25% either 24 or 48 hours after angiography. Patients with CI-AKI had a lower creatinine and a higher eGFR at baseline, but no other independent predictors of CI-AKI could be identified. Kidney function was not different between both groups one and three months after discharge. After a two year follow up the overall incidence of cardiovascular events was 56.5% in the CI-AKI group and 58.8% in the Non CI-AKI group (p = 0.8), the incidence of myocardial infarctions, however, was higher in CI-AKI-patients. Overall survival was also not different between patients with CI-AKI (88.6%) and without CI-AKI (84.7%, p = 0.48). The occurrence of CI-AKI did not have any negative impact on mid-term kidney function, the incidence of cardiovascular events and mortality. Considerable fluctuations of serum creatinine interfere with the presumed diagnosis of CI-AKI. Necessary angiographic procedures should not be withheld in fear of CI-AKI.


Tectorigenin ameliorated high-fat diet-induced nonalcoholic fatty liver disease through anti-inflammation and modulating gut microbiota in mice.
Nonalcoholic fatty liver disease (NAFLD) is a complex pathogenesis of liver disease combined with liver inflammation and gut microbiota dysbiosis. Tectorigenin (Tg) is derived from many plants with excellent anti-inflammation activity. However, the beneficial effect of Tg on NAFLD associated with gut microbiota remained unclear. This study aimed to investigate the underlying beneficial effect of Tg on NAFLD in high-fat diet (HFD)-fed mice. Results showed that Tg alleviated lipid profiles and liver steatosis, and reduced serum lipopolysaccharide (LPS) and total bile acid (TBA) levels. Besides, RT-qPCR and Western blot suggested that Tg alleviated hepatic lipid accumulation through inhibiting the lipogenesis and promoting the lipolysis, prevented gut-derived LPS-induced liver inflammatory via restoring intestinal barrier and restraining pro-inflammatory cytokines release, meanwhile, promoted the BA circulation via activating BA receptor and promoting BA synthesis. Moreover, Tg reverted the HFD-induced gut microbial dysbiosis by promoting the growth of beneficial Akkermansia, and inhibiting the proportions of harmful microbes, including Blautia, Lachnoclostridium, Lachnospiraceae_UCG-006, Roseburia, Romboutsia and Faecalibaculum, which were highly correlated with NAFLD-related parameters in serum and liver. Thus, Tg could attenuate NAFLD through mediating the liver-gut axis, and it could be used as a dietary supplement for NAFLD treatment via its anti-inflammatory and prebiotic effects.


[Evaluation of functional periodicity of the pituitary gland by harmonic analysis.--IV) Circadian prolactin secretion in women with breast cancer].
Secretory periodicity of prolactin (PRL) is preserved in women with breast cancer in spontaneous or surgical menopause. Hormone titres occurring during the day may be occasionally significantly higher in respect to the ones observe in normal controls at the same hours. The periodicity features calculated by the Fourier's method show however normal indices, namely mesor (mean PRL titres in the 24 hours) phase, amplitude and frequency of oscillations.


Milk-flow, ultrasonographic, theloscopic, and histopathological characteristics of the teat in cows with toxic mastitis.
The milk-flow, imaging, and histopathological characteristics of the teat in five cows with toxic mastitis were investigated. Teats were grouped into type I (without gross and histopathological abnormality), type II (no abnormal gross findings, but with histopathological abnormality), and type III (with gross and histopathological abnormality). Normal teats from six cows served as controls. Type II and III teats had lower milk-flow, compared with the controls. Ultrasonography revealed no abnormal findings, except for irregular mucosal surface in type II teats and absence of hyperechoic line along the teat canal in type III teats. The theloscopic findings varied from normal to mucosal abnormalities in type II and III teats. Histopathology demonstrated epithelial changes, congestion, hemorrhage, edema, cellular infiltration, and elastic fiber degradation in type II and III teats, with the type III teats showing severe changes. Toxic mastitis was characterized by impaired milk-flow and various degrees of imaging and histopathological abnormality.


Cholinergic topography in Alzheimer brains: a comparison with changes in the monoaminergic profile.
The topographical distribution of the choline acetyltransferase (ChAT) activity and the number of muscarinic binding sites was studied in the anterio-posterior direction of the caudate nucleus, hippocampus, globus pallidus and putamen of four subjects with senile dementia of Alzheimer type (AD/SDAT) and in the same regions in six controls. Intranuclear gradients were observed both for ChAT and muscarinic receptors. The data obtained were compared with data on noradrenaline (NA) concentration. With longer duration of the disease a decrease was found in the noradrenergic and cholinergic systems. One patient died acutely after a rather short duration of the disease. In this patient no change in ChAT activity was found while the NA concentration was decreased in all brain regions. An upregulation of the number of muscarinic receptors was observed in the caudate nucleus and putamen of all cases, except for the case with the shortest duration of the disease.


Dehydroepiandrosterone status in postmenopausal women is determined by the gene for the vitamin D receptor.
Data documenting the indirect interaction of vitamin D and bone metabolism via hormonal systems are rare. The authors analysed the predictive role of the vitamin D receptor (VDR) gene for circulating sex steroids and their precursors in postmenopausal women. Using the PCR technique, the polymorphic FokI, ApaI, TaqI and BsmI sites of the VDR gene were determined in relation to serum dehydroepiandrosterone sulphate (DHEAS), androstenedione (AD), testosterone, and estradiol levels. After adjustment to body mass and years since menopause, circulating DHEAS was higher in the Ff genotype than in ff (p < 0.001) and FF genotypes (p < 0.05, ANCOVA followed by least significant difference multiple comparison tests). The Ff genotype also contributed to the highest BMD at the hip (p < 0.01 as compared to ff genotype) and at the spine (p < 0.05). No significant associations were found between ApaI, TaqI and BsmI polymorphisms and serum DHEAS or between FokI, ApaI, TaqI or BsmI and serum androstenedione, testosterone or estradiol. The study shows that the VDR gene predicts synthesis and/or metabolism of sexual steroid preursor DHEA in parallel with bone mineral density (BMD). The results indicate that DHEA production and bone mass share a common genetic control through VDR.


Misconceptions and realities about teaching online.
This article is intended to guide online course developers and teachers. A brief review of the literature on the misconceptions of beginning online teachers reveals that most accept the notion that putting one's lecture notes online produces effective learning, or that technology will make education more convenient and cost-effective for all concerned. Effective online learning requires a high level of responsibility for learning on the part of students and a reduction of the teacher-student power differential. This, in turn, has major implications for faculty and course development, student selection criteria, the cost of instruction, and the outcomes of education. Effective online teaching focuses on processes of learning rather than outcomes, and is consistent with modern principles of learning that emphasize focusing on issues of high interest to learners, teaching students to use skills of active and effective learning, providing prompt feedback, and enabling students to establish learning goals and employ alternative paths to achieving those goals. Multiple ways of operationalizing these goals online are presented. Tips are offered concerning selection of students who are capable of benefiting from the online experience, developing curriculum that is user-friendly, using resources that stimulate good writing and critical thinking, and limiting class size to a manageable number.


Intercellular adhesion molecule 1 (ICAM1) Lys56Met and Gly241Arg gene variants, plasma-soluble ICAM1 concentrations, and risk of incident cardiovascular events in 23,014 initially healthy white women.
The objective of this study was to examine the association of 2 nonsynonymous intercellular adhesion molecule 1 (ICAM1) gene variants (Lys56Met and Gly241Arg) with baseline plasma soluble ICAM1 concentrations and with risk of total and selected cardiovascular disease (CVD) events in a prospective cohort of 23 014 apparently healthy white American women followed for 10 years. ICAM1 variations have been associated with plasma soluble ICAM1 concentrations and inflammatory conditions, including atherosclerosis. However, to date, no large prospective, genetic-epidemiological data set is available that would allow evaluation of the degree of association of these gene variants with risk of CVD. ICAM1 genotypes and baseline plasma soluble ICAM1 concentrations were determined. The primary outcome measure was a composite CVD end point (incident ischemic stroke, myocardial infarction, or death due to ischemic CVD); other measures were incident ischemic stroke, myocardial infarction, and coronary revascularization. During follow-up, 751 total incident CVD events, 187 incident myocardial infarction cases, 203 incident ischemic stroke cases, and 433 coronary revascularization events occurred. All observed genotype frequencies were in Hardy-Weinberg equilibrium across the whole sample population. We found baseline plasma soluble ICAM1 concentrations to be significantly reduced among carriers of Met56 allele (P<0.0001) and Arg241 allele (P<0.0001) as compared with the respective noncarriers of these variants. However, the polymorphisms tested and the respective haplotypes were neither associated with overall risk nor with risk with risk for selected CVD events regardless of whether analyses were adjusted for traditional CVD risk factors/confounders (all P values >0.10). In this large prospective study, we found an association of the nonsynonymous gene variants tested with reduced baseline plasma soluble ICAM1 concentrations. However, no evidence was found for an association of the gene variants tested with the overall or selected CVD end points examined, suggesting that these variants may not add useful aids to current risk predictors for early assessment of cardiovascular events.


Laboratory Evaluations of the Fractions Efficacy of Annona senegalensis (Annonaceae) Leaf Extract on Immature Stage Development of Malarial and Filarial Mosquito Vectors.
Within the framework to control mosquitoes, ovicidal, larvicidal and pupicidal activity of Annona senegalensis leaf extract and its 4 fractions against Anopheles gambiae and Culex quinquefasciatus were evaluated in the laboratory conditions. Ovicidal test was performed by submitting at least 100 eggs of mosquitoes to 125, 250, 500, 1000 and 2000 ppm concentrations, while larvicidal and pupicidal effects were assessed by submitting 25 larvae or pupae to the concentrations of 2500, 1250, 625 and 312.5 ppm of plant extract or fractions of A. senegalensis. The eggs of An. gambiae were most affected by N-hexane (0.00% hatchability) and chloroform (03.67% hatchability) fractions compared to Cx. quinquefasciatus where at least 25 % hatchability were recorded at 2000 ppm. For larvicidal test, N-hexane (LC50= 298.8 ppm) and chloroform (LC50= 418.3 ppm) fractions were more effective than other fractions on An. gambiae larvae while, a moderate effectiveness was also observed with N-hexane (LC50= 2087.6 ppm), chloroform (LC50= 9010.1 ppm) fractions on Cx. quinquefasciatus larvae. The highest mortality percent of the pupae were also recorded with N-hexane and chloroform fractions on An. gambiae at 2500 ppm. As for Cx. quinquefasciatus only 50 % and 36 % mortality were recorded with N-hexane and chloroform fractions respectively. The extract of A. senegalensis was toxic on immature stage of mosquito species tested. By splitting methanolic crude extract, only N-hexane and chloroform fractions were revealed to possess a mosquitocidal effects and could be considered and utilized for future immature mosquito vectors control.


[Place of bisphosphonates in the primary andsecondary prophylaxis of osteoporotic fractures: the role of parenteral therapy--proposal to modify the standards of treatment].
Oral bisphosphonates are currently known as medicines of a first choice in the treatment of osteoporosis and in preventing age-related fractures. However, despite their advantages, these medicines are not free of limitations. The most significant one is a complicated way of tablet administration, requiring from patients to remain upright position and to take a tablet before a meal. This may make the administration of other, chronic medicines, such as thyroid hormones, more difficult. Complications of the therapy include dyspepsia and gastrointestinal disorders. Approximately 48% of individuals taking bisphosphonates once a week resign from therapy within one year from the beginning of the treatment. There is a group of individuals who cannot take bisphosphonates orally at all. The alternative here is an intravenous injection. Therefore, there is a need for modifications of the existing therapeutic standards for osteoporosis. It is also necessary to emphasise the significance of intravenous medicines in the treatment of this disease.


Neutrophils do not contribute to infarction, oxidative stress, and NO synthase activity in severe brain ischemia.
Polymorphonuclear leukocytes (PMNs) were reported to contribute to ischemia-reperfusion-induced brain damage. The present work examined whether PMN infiltration is deleterious in a severe model of transient focal cerebral ischemia and in which part PMNs contribute to oxidative stress and nitric oxide (NO) production. A 20-min occlusion of the left middle cerebral artery and both common carotid arteries was performed in rats. Infarction was maximal 24 h after reperfusion, while accumulation of PMNs in infarcted tissue was not significant before 48 h. Moreover, neutropenia induced by vinblastine (0.5 mg/kg iv) significantly decreased by 60-80% PMN infiltration 48 h after reperfusion but did not reduce the infarct volume. Thus PMNs do not contribute to cerebral injury in our model. Furthermore, decreased PMN infiltration modified neither oxidative stress evaluated by glutathione concentrations nor NO synthase activities 48 h after reperfusion. In conclusion, our results suggest that PMNs are not involved in severe cerebral ischemia and that anti-PMN strategies may be inefficient in some pathological conditions.


The extraction and analysis of cylindrospermopsin from human serum and urine.
The naturally derived cyanotoxin, cylindrospermopsin (CYN), has been detected in freshwater systems worldwide and poses a threat to human health. The methods for the extraction and detection of this toxin in source water are well documented, but methods for CYN determination in exposed individuals have not been investigated. In this study, the extraction and detection of CYN from two different matrices, serum and urine, was explored. Both serum and urine matrices inherently produce interference with analytical analyses and require extensive clean-up. Methods for extraction of CYN from both matrices were developed and validated using fortified samples. Serum extraction included homogenization followed by protein precipitation and solid phase extraction (SPE). Urine samples were processed using filtration, pH manipulation, and SPE. Analyses using a commercially available enzyme-linked immunosorbent assay (ELISA) and liquid chromatography coupled with mass spectrometry (LC/MS/MS) were assessed. Matrix effects inhibited ELISA's use as a quantitative tool for both matrices. LC/MS/MS was determined to be the most effective and reproducible means to detect and quantify CYN. The method detection limits determined in this study using LC/MS/MS were 0.25 and 0.50 ng mL⁻¹ for serum and urine, respectively. This method can be used to test individuals exposed to blooms of cyanobacteria producing CYN.


Calorie restriction as an intervention in ageing.
Ageing causes loss of function in tissues and organs, is accompanied by a chronic inflammatory process and affects life- and healthspan. Calorie restriction (CR) is a non-genetic intervention that prevents age-associated diseases and extends longevity in most of the animal models studied so far. CR produces a pleiotropic effect and improves multiple metabolic pathways, generating benefits to the whole organism. Among the effects of CR, modulation of mitochondrial activity and a decrease in oxidative damage are two of the hallmarks. Oxidative damage is reduced by the induction of endogenous antioxidant systems and modulation of the peroxidability index in cell membranes. Mitochondrial activity changes are regulated by inhibition of IGF-1 and Target of Rapamycin (TOR)-dependent activities and activation of AMP-dependent kinase (AMPK) and the sirtuin family of proteins. The activity of PGC-1α and FoxO is regulated by these systems and is involved in mitochondria biogenesis, oxidative metabolism activity and mitochondrial turnover. The use of mimetics and the regulation of common factors have demonstrated that these molecular pathways are essential to explain the effect of CR in the organism. Finally, the anti-inflammatory effect of CR is an interesting emerging factor to be taken into consideration. In the present revision we focus on the general effect of CR and other mimetics in longevity, focusing especially on the cardiovascular system and skeletal muscle.


Cadmium exposure impairs skeletal muscle function by altering lipid signature and inducing inflammation in C57BL/6J mice.
Cadmium (Cd) is a well-known environmental pollutant with high toxicity. Despite a variety of studies have demonstrated that Cd exposure induces multiple organ damages in humans, there is still a lack of knowledge of Cd induced skeletal muscle impairment. Exercise is a non-invasive, effective intervention to improve human health and combat diseases. In this study, we aimed to evaluate the toxic effects of Cd exposure on skeletal muscle function and explore the possibility of exercise for attenuating skeletal muscle toxicity of chronic Cd exposure. C57BL/6J mice were exposed to Cd via drinking water containing CdCl2 10 mg/dL for 8 weeks while a moderate exercise was daily induced by a motorized treadmill to mice. It was found that Cd exposure significantly reduced the ratio of gastrocnemius and body weight, decreased mouse exercise capacity, weakened muscle strength, promoted lipid accumulation and up-regulated pro-apoptotic genes in the skeletal muscle. Non-targeted lipidomics analysis indicated that Cd exposure disturbed lipid metabolism, altered lipid signatures and elevated pro-inflammatory lipid species in the skeletal muscle. Moreover, Cd exposure evoked an intense inflammatory response in the skeletal muscle by up-regulating pro-inflammatory cytokine production such as Eotaxin (CCL11), TNF-α, IL-1β, IL-6, RANTES (CCL5) and so on. Notably, treadmill exercise effectively protected against Cd induced skeletal muscle impairment indicated by the effects of inhibiting lipid metabolism disturbance, suppressing pro-inflammatory cytokine production and preserving skeletal muscle function. These results demonstrated that environment relevant Cd exposure impairs skeletal muscle function and exercise effectively antagonizes the Cd toxicity in the skeletal muscle and preserves skeletal muscle function. This study provided the novel evidence for unraveling Cd toxicity on the skeletal muscle function and highlighted the possibility of considering exercise as a countermeasure for Cd induced skeletal muscle impairment at population level.


Sonic vibration induces the nucleation of actin in the absence of magnesium ions and cytochalasins inhibit the elongation of the nuclei.
Polymerization of actin was completely inhibited by metal chelating agents, such as EDTA or diaminocyclohexanetetraacetic acid, even in the presence of 0.1 M KCl and excess ATP. Addition of 1 mM MgCl2, but not CaCl2, caused full polymerization in the presence of 10 mM diaminocyclohexanetetraacetic acid, suggesting that micromolar concentrations of Mg ions are required for the polymerization of actin. However, it turned out that sonic vibration induced a very rapid polymerization of actin in the absence of Mg ions. The sonication-induced polymerization of actin was greatly inhibited by cytochalasins D and B, and partially by beta-actinin. This can be explained by assuming that the fast growing ends of the formed nuclei are blocked by the cytochalasins, and the slowly growing ends with beta-actinin. The elongation of added F-actin fragments was also similarly inhibited by the cytochalasins and beta-actinin in the absence of Mg ions. It appears that sonic vibration enhances nuclei formation of actin monomers by mechanical agitation in the absence of Mg ions, which stabilize formed nuclei.


Mutational analysis of sites in sepiapterin reductase phosphorylated by Ca2+/calmodulin-dependent protein kinase II.
Sepiapterin reductase (SPR) catalyzes the last step in the pathway of tetrahydrobiopterin biosynthesis in tissues. SPR is phosphorylated by Ca2+-dependent protein kinases, which indicates that Ca2+-activated protein kinases may play a role in the regulation of SPR in vivo. Phosphorylation sites of rat sepiapterin reductase (rSPR) by Ca2+/calmodulin-dependent protein kinase II were determined in the present study. Using specific monoclonal anti-phospho-Ser and -Thr antibodies, we found that only Ser residues of rSPR were phosphorylated. We constructed several point mutants of SPR by systematically replacing the three Ser residues by Ala ones. These mutants showed that all three Ser residues, i.e. S46, S196, and S214, of rSPR were phosphorylated. We also recognized that only Ser-213 of human SPR was phosphorylated. Each of these serine residues in SPR was found in the consensus sequence (Arg-X-X-Ser/Thr) of the phosphorylation site.


Initial evaluation of chest pain.
Chest pain is among the most frequently evaluated presenting complaints in the emergency department (ED). Diagnostic etiologies range from benign to life-threatening. Failure to diagnose the life-threatening chest emergencies-specifically acute coronary syndrome, aortic dissection, and pulmonary embolism-can lead to catastrophic medical and legal outcomes for the patient and physician respectively. This article focuses on clinical and risk management strategies to minimize misdiagnosis and produce favorable medical and medicolegal outcomes.


Treatment strategies for a rapidly evolving landscape in chronic lymphocytic leukemia management.
With the advent of targeted therapies for chronic lymphocytic leukemia (CLL), treatment choice has expanded and patients are living longer. Careful consideration is needed regarding treatment duration and sequence, how best to meet patients' needs, balancing toxicities while improving long-term survival and maximizing depth of response. This review addresses these considerations and discusses current targeted treatment dilemmas. Targeted therapies have dramatically transformed the CLL treatment landscape. Two treatment paradigms have emerged using B-cell lymphoma 2 inhibitors (BCL2i) and Bruton's tyrosine kinase (BTK): (i) fixed duration and (ii) continuous treatment. The BCL2i venetoclax can attain deep remissions with a fixed-duration approach, resulting in high rates of undetectable minimal residual disease (uMRD) in treatment-naïve and relapsed/refractory (R/R) patients with CLL. BTKis such as ibrutinib and acalabrutinib achieve high objective response rates and long-term disease control, although they rarely attain complete response or uMRD status as monotherapy. Numerous studies are evaluating the clinical utility of BTKi and BCL2i as combination therapies, where deep remissions have been found to occur. MRD status may also be a useful marker for deciding when to stop continuous therapy, and randomized trials on MRD-guided treatment strategies are currently ongoing. The current treatment choice between continuous or fixed-duration therapy should be based on comorbidities, risks, preferences, and treatment goals, whilst areas of emerging clinical interest include the potential utility of BTKi-BCL2i combination therapies, as well as an MRD-guided treatment strategies in the future.


Differential expression of HLA-DR and DR-linked determinants on human leukemias and lymphoid cells.
Leukemic and normal hemopoietic cells were examined with the monoclonal anti-bodies DA2 and Genox 353 for the presence of HLA-DR and DR-linked (DC/MB) determinants, respectively. Although most non-T acute leukemias and leukemic cell lines expressed the monomorphic DR determinant detected by DA2, fewer than expected expressed the DR-linked polymorphic specificity detected by Genox 353. TdT+ lymphoid precursors from normal bone marrow were also DA2+ but Genox 353-. T cells and thymocytes which were DA2-, Genox 353- became DA2+, Genox 353+ after activation in vitro. Immunoprecipitation using DA2 and Genox 353 gave bands on polyacrylamide gel-electrophoresis which were of different molecular weights. In addition, DA2 could absorb out Genox 353 determinants from a cell lysate whereas Genox 353 could not absorb out DA2 determinants. It is concluded that DA2 and Genox 353 detect HLA-DR and DR-linked (DC1/MB1) determinants, respectively, and that these are differentially expressed on hemopoietic cells during differentiation.


Ethinyl estradiol, not progestogens, reduces lamotrigine serum concentrations.
To study the interaction between lamotrigine (LTG) and hormonal contraception. LTG serum concentrations of female patients using either no hormonal contraception (n=18), an ethinyl estradiol (EE)-containing (n=11), or a progestogen (PG)-only-containing compound (n=16) were analyzed. Patients were recruited prospectively, and blood samples were drawn during drug fasting and at steady-state conditions. Comedication with enzyme inducers, valproate, topiramate, or sertraline was not allowed. Some patients changed groups and thus served as their own controls. Samples were analyzed by a gas chromatography/ mass spectroscopy method. The Mann-Whitney U test was used for statistical comparison of the groups. The LTG serum concentration-to-dose ratio (CDR), expressed as (mg/L)/(mg/d) was significantly lower in women using EE than in the control group (mean+/-SD, 0.010+/-0.004 vs. 0.017+/-0.006; p=0.003). The CDR in women using PG was 0.02+/-0.007, which was not statistically different from controls. No difference was found in CDR between women using either oral, topical, or parenteral PG. Five women switched from the control to the EE group and experienced a considerable reduction in CDR. An increase of the CDR toward control level was seen in the two women who changed from EE to PG. It is the EE component of oral contraceptives that interacts with LTG. The PG-only compounds did not alter LTG serum concentrations in this study. These findings should be considered when counselling women with epilepsy in the childbearing ages.


New π-arene ruthenium(II) piano-stool complexes with nitrogen ligands.
The synthesis, characterization, DNA interaction and antiproliferative behavior of new π-arene ruthenium(II) piano-stool complexes with nitrogen ligands are described. Three series of organometallic compounds of formulae [RuCl(2)(η(6)-p-cym)L] were synthesized (with L=2-, 3- or 4-methylpyridine; L=2,3-, 2,4-, 2,5-, 3,4-, 3,5-dimethylpyridine and L=1,2-, 1,3- 1,4-methylaminobenzene). The crystal structures of [RuCl(2)(p-cym)(4-methylpyridine)], [RuCl(2)(p-cym)(3,4-dimethylpyridine)] and [RuCl(2)(p-cym)(1,4-methylaminobenzene)] were resolved and the characterization was completed by spectroscopic UV-vis, FT-IR and (1)H NMR studies. Electrochemical experiments were performed by cyclic voltammetry to estimate the redox potential of the Ru(II)/Ru(III) couple. The interaction with plasmid pBR322 DNA was studied through the examination of the electrophoretical mobility and atomic force microscopy, and interaction with ct-DNA by circular dichroism, viscosity measurements and fluorescence studies based on the DNA-ethidium bromide complex. The antiproliferative behavior of the series with L=methylpyridine was assayed against two tumor cell lines, i.e. LoVo and MiaPaca. The results revealed a moderate cytotoxicity with a higher activity for the LoVo cell line compared to the MiaPaca one.


PP2Cm overexpression alleviates MI/R injury mediated by a BCAA catabolism defect and oxidative stress in diabetic mice.
Diabetic patients are sensitive to myocardial ischemia-reperfusion (MI/R) injury. During diabetes, branched-chain amino acid (BCAA) catabolism is defective and mitochondrial phosphatase 2C (PP2Cm) expression is reduced. This study aims to elucidate the relationship between PP2Cm downregulation and BCAA catabolism defect in diabetic mice against MI/R injury. PP2Cm was significantly downregulated in hearts of diabetic mice. The cardiac function was improved and the myocardial infarct size and apoptosis were decreased in diabetic mice overexpressing PP2Cm after MI/R. In diabetic mice, the cardiac BCAA and its metabolites branched-chain keto-acids (BCKA) levels, and p-BCKDE1α (E1 subunit of BCKA dehydrogenase)/BCKDE1α ratio were increased while the BCKD activity was decreased. Treatment of diabetic mice subjected to MI/R injury with BT2, a BCKD kinase (BDK) inhibitor, alleviated the BCAA catabolism defect, and improved the cardiac function alongside reduced apoptosis. PP2Cm overexpression alleviated the BCAA catabolism defect and MI/R injury. Similarly, MnTBAP ameliorated the oxidative stress and MI/R injury. BCKA treatment of H9C2 cells under simulated ischemia/reperfusion (SI/R) injury significantly decreased cell viability and increased LDH release and apoptosis. These effects were alleviated by BT2 and MnTBAP treatments. These results suggested that PP2Cm directly mediates the BCAA catabolism defect and oxidative stress observed after MI/R in diabetes. Overexpression of PP2Cm alleviates MI/R injury by reducing the catabolism of BCAA and oxidative stress.


Phenylalanine 368 of multidrug resistance-associated protein 4 (MRP4/ABCC4) plays a crucial role in substrate-specific transport activity.
Multidrug resistance-associated protein 4 (MRP4) is a membrane transporter that mediates the cellular efflux of a wide range of anionic drugs and endogenous molecules. MRP4 transport can influence the pharmacokinetics of drugs and their metabolites, therefore more knowledge about the molecular determinants important for its transport function would be of relevance. Here, we substituted amino acids Phe(368), Trp(995), and Arg(998) with conservative or non-conservative residues, and determined the effect on transport of the model substrates estradiol 17-β-d-glucuronide (E(2)17βG), cyclic guanosine monophosphate (cGMP), methotrexate (MTX), and folic acid into membrane vesicles isolated from baculovirus transduced HEK293 cells overexpressing the mutant MRP4 proteins. This revealed that all Arg(998) mutations appeared to be deleterious, whereas the effect of a Phe(368) or Trp(995) replacement was dependent on the amino acid introduced and the substrate studied. Substitution of Phe(368) with Trp (F368W) induced a gain-of-function of E(2)17βG transport and a loss-of-function of MTX transport, which could not be attributed to an altered substrate binding. Moreover, we did not observe any modification in ATP or ADP handling for F368W. These results, in combination with docking of substrates in a homology model of MRP4 in the inward- and outward-facing conformation, suggest that Phe(368) and Trp(995) do not play an important role in the initial binding of substrates. They, however, might interact with the substrates during rearrangement of helixes for substrate translocation, funneling the substrates to the exit site in the outward-facing conformation.


First case report of pustules associated with Escherichia fergusonii in the chinese pangolin (Manis pentadactyla aurita).
Escherichia fergusonii is a common conditionally pathogenic bacterium that infects humans and animals. E. fergusonii has been reported to cause diarrhea, respiratory disease, and septicemia, but it is rarely reported to cause skin infections in animals. E. fergusonii has been isolated from the skin and muscular tissue of Chinese pangolin (Manis pentadactyla aurita). To date, there have been no reports of Chinese pangolins with clinical signs of skin diseases. This case report describes the clinical case of a subadult (bodyweight: 1.1 kg) female Chinese pangolin from wild rescue with pustules and subcutaneous suppurative infection due to E. fergusonii in the abdominal skin. Bacterial culture, Biochemical analysis, PCR and histopathology were utilized to identify the bacteria in the pustule puncture fluid and infected tissue. To the best of our knowledge, this is the first report of E. fergusonii-related pustules on a Chinese pangolin. This case report presents the first observed skin infection in a Chinese pangolin. E. fergusonii infection should be considered as a possible differential diagnosis of pustules and subcutaneous suppurative skin conditions in Chinese pangolins, and we also provide several recommendations for the diagnosis and treatment of this disease.


BMP-4 upregulates Kit expression in mouse melanoblasts prior to the Kit-dependent cycle of melanogenesis.
Genes encoding Kit and the Kit ligand (KL) play essential roles in the differentiation of melanoblasts. We previously established three immortal but distinct cell populations of mouse neural crest (NC) cells. NCCmelb4M5 cells do not express Kit and grow independently of KL; they have the potential to differentiate into NCCmelb4 cells, which are Kit-positive melanocyte precursors. NCCmelan5 cells show the characteristics of differentiated melanocytes. All three cell lines demonstrated bone morphogenetic protein (BMP) receptor expression. BMP-4 upregulated Kit protein and mRNA expression in most immature NCCmelb4M5 cells. Noggin, a BMP-4 antagonist, dramatically decreased the Kit expression induced by BMP-4. Western blot analysis revealed that extrinsic BMP-4 leads to the phosphorylation of Smads in NCCmelb4M5 cells. Using transfected Kit-promoter reporter, we showed BMP-4 could activate Kit promoter in transfected NCCmelb4M5 cells. We conclude that BMP-4 is active and is involved in the regulation of Kit expression on most immature melanocyte precursors. We further investigated the influence of BMP-4 in vitro using primary NC cells cultured from wild-type mice. Addition of BMP-4 to the medium increased the number of Kit-positive cells compared to diluent-treated controls. We have identified BMP-4 as an important factor for prenatal Kit-negative melanoblasts just prior to entering the Kit-dependent cycle of melanogenesis.


Reliability of 2 protocols for assessing pressure pain threshold in healthy young adults.
The purposes of this study were to determine whether there were differences in mean values or reliability for 2 frequently used protocols for pressure pain threshold (PPT) and to calculate how large a difference in PPT is necessary to be 95% confident that a real change has occurred. Thirteen participants (8 females) aged 22.3 (±2.3) years from a university community were included. Two testers evaluated participants using 2 protocols, in which PPT was measured 3 times at 8 different body locations. The "cluster protocol" consisted of 3 successive measurements at each location with a 30-second rest between each measurement. The "circuit protocol" consisted of 1 measurement taken at each anatomical location until "the circuit" was complete and then repeated a total of 3 times. A 2-way analysis of variance did not reveal significant differences between protocols at any body location (P = .46-.98). Intertester reliability was good to excellent for all locations (intraclass correlation coefficient, 0.84-0.96), and limits of agreement ranged from 108 to 223 kPa. Either the cluster or circuit protocol can be used to measure PPT in clinical or research setting. A difference of 160 kPa is considered sufficient to indicate a real difference between repeated measures of PPT regardless of protocol used for testing.


Medical risks in older pilots: a systematic review on incapacitation and age.
Our ageing society faces an ageing work force. The target of this systematic review was to analyse whether pilots have a measurable age-dependent increased risk of incapacitation due to medical reasons. Publications listed in PubMed, NCBI and EMBASE were identified using defined terms. Two independent raters analysed 2,342 retrieved publications by predefined criteria. Ten publications met the inclusion criteria. Four publications use a similar numerator (in-flight incapacitation) and identical denominator (flight hours) and show in-flight incapacitation of pilots happening 0.19-0.45 times/10(6) flight hours. Two of these studies did not analyse the possible correlation of incapacitation and age, and two did not use the denominator flight hours here. Age dependency of incapacitation is analysed in seven publications: Three analyse in-flight incapacitation and four analyse general incapacitation to fly. All but one--the only one including professional pilots older than 60 years--show an age-depending increase in incapacitation. The increase in in-flight incapacitation is far less than the increase in general flight incapacitation. Medical in-flight incapacitation is a very rare event. Whether the increase in in-flight incapacitation results in an increase in accidents or can be compensated for by error reduction through experience cannot be answered. A register of all pilots with a clear identification system to follow their career and health, their accidents and impairments, might help to reconsider the grounding of pilots over 60 and to define better criteria than mere age.


[Medical care center structures in the outpatient sector: a model for the future of internal medicine?]
Since the early 2000s, legislators have allowed the establishment of medical care centers to supplement and increase the flexibility of medical cooperation models. Several legal changes in subsequent years were unable to prevent that, contrary to the original intention, almost 90% of the newly founded facilities were established in urban cores and medium-sized centers; that concentration processes and monopolization were encouraged; and that the freedom of choice for patients was restricted. In order to counter the risk of undermining the free exercise of the medical profession and the dictates of economics over patient-oriented medicine in the outpatient sector, corporations, scientific societies, and professional associations are demanding more transparency and narrower limits for non-physician capital investors. There are currently more than 3000 medical care centers in Germany employing around 20,000 physicians, many of whom are internal medicine specialists. Regionally networked medical care center structures combine the advantages of optimized patient care with the growing desire of the younger generation of physicians for flexible working conditions within employment. With increasing acceptance on the part of the medical profession, networked medical care centers are able to create local structures for the expansion of modern intersectoral care and, at the same time, can be available for outpatient specialist training in internal medicine.


Associations of depression and seasonality with morning-evening preference: Comparison of contributions of its morning and evening components.
Despite predominance of positive findings on associations of morning-evening preference with seasonality and depression, it remains to be clarified whether morning and evening components of this preference equally contribute to these associations and whether these associations persist after accounting for confounding variables. Data on retrospectively reported seasonal changes in well-being, mood, and behaviors were collected from 2398 residents of West Siberia, South and North Yakutia, Chukotka, Alaska, and Turkmenistan. Other self-reports included mental and physical health, sleep duration, and adaptabilities of the sleep-wake cycle. Depression was found to be linked to morning rather than evening component of morning-evening preference, i.e., morning lateness. Morning lateness was also linked to retrospectively reported degree of seasonal changes rather than to severity of problems associated with such changes. Variation in morning-evening preference explained not more than 2% and 4% of the total variation in depression and seasonality, respectively. The associations became even weaker but remained significant after accounting for other differences between respondents, such as their gender, age, physical health, and adaptability of their sleep-wake cycle. These results have practical relevance for understanding of the roles playing by morning earliness and insensitivity to seasonal changes in the environment to protection against different mood disorders.


Rheological studies on calcium-sensitive gelation of actin filaments by actinogelin.
Actinogelin, a regulatory protein of cell motility, enhanced gelation of actin filaments in the absence of calcium ions, only on standing still or with very low velocity gradients ( less than 0.1 s-1). The Ca2+-sensitive action of actinogelin on action filaments was dependent on a weak external force. In the presence of a micromolar level of Ca2+, actinogelin did not affect the network formation of actin filaments at all.


Hexachlorocyclohexane differentially alters the antioxidant status of the brain regions in rat.
Hexachlorocyclohexane (HCH), a highly persistent organochlorine insecticide, is neurotoxic at acute doses and causes degenerative effects on chronic exposure. HCH has been reported to induce oxidative stress in cells and tissues. Mammalian brain is sensitive to oxidative stress which is implicated in neurodegenerative diseases. Effect of HCH on the brain regions, cortex, cerebellum, midbrain and brainstem, has been investigated by studying the response of antioxidant enzymes in rats treated orally with HCH at 25 and 100mg/kg b.w. for 2 weeks. Lipid peroxidation and glutathione depletion was seen in all the brain regions of HCH treated rats. The brain regions showed distinct variation in the antioxidant enzyme activities. Activities of glutathione peroxidase, glutathione reductase, glutathione-S-transferase and catalase were markedly induced whereas superoxide dismutase was inhibited at higher dose in all the brain regions. Marked induction and inhibition of the antioxidant enzymes, especially in the cortex and to varying degrees in other brain regions, was seen in HCH treated rats. These biochemical changes suggest vulnerability to oxidative stress in the brain is region-specific. Whether these changes are adaptive or compromise the capacity of the brain to deal with the HCH-induced oxidative stress that could lead to degenerative neurotoxic manifestations remain to be understood.


Methyl-prednisolone in neurologic complications of Mycoplasma pneumonia.
In patients with Mycoplasma pneumonia extrapulmonary manifestations such as encephalitis, meningitis, cerebellar and brain stem involvement, cranial nerve lesions, peripheral neuropathy, polymyositis have been observed. We report a 16-year-old girl with M. pneumonia infection, acute behavioral changes and coma. Treatment with high dose methyl-prednisolone and clarithromycin led to rapid clinical improvement.


Barriers to metabolic care for adults with serious mental illness: provider perspectives.
This study assessed barriers to metabolic care for persons with serious mental illness (SMI) by surveying experienced healthcare providers. Sixty-eight medical, mental health, and other stakeholders who care for patients with SMI attended a CME conference focused on medical management of SMI patients in 2007. They completed a 27-item survey assessing barriers to and systemic responsibility for metabolic care. The top three ranked barriers were: "separate mental health and primary care systems," "patient's lack of resources," and "[mental health] providers are not trained to do basic primary care." Results indicated that ratings of CMHC responsibility for SMI metabolic care (M = 5.2, SD = 1.5) were significantly lower than ratings of public health (M = 5.7, SD = 1.4), t(66) = 2.3, p = 0.027, and primary care providers (M = 6.3, SD = 1.1), t(67) = 4.7,p <0.001. Experienced providers identified a lack of integrated care and patient characteristics as important barriers to metabolic care and concluded that the primary care and public health systems are primarily responsible for metabolic treatment.


Standardization of basophil degranulation for pharmacological studies.
There is a need of a standard basophil degranulation test for diagnosis and for immunopharmacological studies. In order to obtain a sufficient concentration of basophils blood was sedimented at 1 g which gave a yield of 1500-3000 basophils/microliter instead of 50/microliter in whole blood. As the course of degranulation is exponential, it can be linearised using a logarithmic approximation Y = A0 + A1 log D where D is the allergen concentration. The application of this mathematical method permitted the collection of statistical information about the test itself. The coefficient of variation was less than 10%. The test can be used to compare the allergenic potency of different extracts of the same allergen.