Adhesive mechanisms governing interferon-producing cell recruitment into lymph nodes.
Natural interferon-producing cells (IPCs) are found in peripheral lymph nodes (PLNs), where they support NK cell, T cell, and B cell responses to pathogens. However, their route of entry and the adhesive mechanisms used to gain access to PLNs remain poorly defined. We report that IPCs can enter PLNs via a hematogenous route, which involves a multistep adhesive process, and that transmigration is enhanced by inflammation. Results indicate that L-selectin on IPCs is required for efficient attachment and rolling on high endothelial venules in vivo in both nonstimulated and inflamed PLNs. IPCs, however, also possess functional ligands for E-selectin that contribute to this process only in the latter case. In conjunction with selectin-mediated adhesion, both beta(1)- and beta(2)-integrins participate in IPC attachment to the inflamed vessel wall, whereas chemotaxis relies in part on the chemokine receptor CCR5. Identification of the adhesive machinery required for IPC trafficking into PLNs may provide opportunities to regulate immune responses reliant on the activity of these cells.


Feasibility of Consumer Grade GNSS Receivers for the Integration in Multi-Sensor-Systems.
Various GNSS applications require low-cost, small-scale, lightweight and power-saving GNSS devices and require high precision in terms of low noise for carrier phase and code observations. Applications vary from navigation approaches to positioning in geo-monitoring units up to integration in multi-sensor-systems. For highest precision, only GNSS receivers are suitable that provide access to raw data such as carrier phase, code ranges, Doppler and signal strength. A system integration is only possible if the overall noise level is known and quantified at the level of the original observations. A benchmark analysis based on a zero baseline is proposed to quantify the stochastic properties. The performance of the consumer grade GNSS receiver is determined and evaluated against geodetic GNSS receivers to better understand the utilization of consumer grade receivers. Results indicate high similarity to the geodetic receiver, even though technical limitations are present. Various stochastic techniques report normally distributed carrier-phase noise of 2 mm and code-range noise of 0.5-0.8 m. This is confirmed by studying the modified Allan standard deviation and code-minus-carrier combinations. Derived parameters serve as important indicators for the integration of GNSS receivers into multi-sensor-systems.


[Inflammatory and neoplastic cholangiopathies.]
The biliary tree consists of mature epithelial cells called cholangiocytes and is subdivided in intra and extrahepatic bile ducts. They facilitate the secretion and modification of the bile constituents and act as transport ducts of bile to the intestine. The alteration of the normal function of cholangiocyte, can lead to the development of multiple biliary diseases, known as cholangiopathies, generally chronic, with a progressive course and which often are lacking of an effective treatment, determining a poor prognosis, even lethal, for the patient. These cholangiopathies have peculiar characteristics both for onset and clinical course. The pathogenetic processes affecting cholangiocytes are not yet fully known. Depending on their nature, these diseases are further subdivided into genetic, idiopathic, which include primary biliary cholangitis, primary sclerosing cholangitis and associated IgG4 cholangitis and malignant such as cholangiocarcinoma or mixed hepato-cholangiocarcinoma. This review is focused on the new insights on the pathophysiological and molecular mechanisms involved in the liver damage cascade which provide the basis of novel therapeutic approaches for these cholangiopathies.


Association Between Endometriosis and Hypercholesterolemia or Hypertension.
An altered hormonal or chronic systemic inflammatory milieu characterizing endometriosis may result in a higher risk of hypercholesterolemia and hypertension. Conversely, elevated low-density lipoprotein in hypercholesterolemia and chronic systemic inflammation resulting from hypertension may increase the risk of endometriosis. We assessed the association of laparoscopically confirmed endometriosis with hypercholesterolemia and hypertension in a large prospective cohort study. In 1989, 116 430 registered female nurses aged 25 to 42 completed the baseline questionnaire and were followed for 20 years. Multivariable Cox proportional hazards models were applied. In 1989, there were 4244 women with laparoscopically confirmed endometriosis and 91 554 women without. After adjusting for demographic, anthropometric, family history, reproductive, dietary, and lifestyle risk factors prospectively, comparing women with laparoscopically confirmed endometriosis to women without, the relative risks were 1.25 (95% confidence interval, 1.21-1.30) for development of hypercholesterolemia and 1.14 (95% confidence interval, 1.09-1.18) for hypertension. Conversely, the relative risks of developing laparoscopically confirmed endometriosis were 1.22 (95% confidence interval, 1.15-1.31) comparing women with hypercholesterolemia to women without and 1.29 (95% confidence interval, 1.18-1.41) comparing women with hypertension to women without. The strength of associations of laparoscopically confirmed endometriosis with hypercholesterolemia or hypertension was strongest among women aged ≤40 and weakened as age increased (P values for interaction <0.001). We observed that ≈45% of the associations between endometriosis and hypercholesterolemia and hypertension could be accounted for by treatment factors after endometriosis diagnosis, including greater frequency of hysterectomy/oophorectomy and earlier age for this surgery. In this large cohort study, laparoscopically confirmed endometriosis was prospectively associated with increased risk of hypercholesterolemia and hypertension. Conversely, hypercholesterolemia and hypertension were prospectively associated with higher risk of laparoscopically confirmed endometriosis.


Anterior petrosal (Kawase) approach to petroclival meningioma: 2-dimensional operative video.
Petroclival meningiomas are challenging lesions that can be treated with several surgical approaches. The authors present a 66-year-old woman with a 1.6-cm left petroclival meningioma that was initially observed and then radiated after it grew 8 years later. Despite radiation, the tumor continued to grow to 4 cm; therefore, the patient was referred to the authors' institution. A left anterior petrosal (Kawase) approach was performed. Postoperatively, the patient had transient cranial nerve IV and VI palsy that improved. The case presentation, surgical anatomy, operative technique, postoperative course, and different surgical approaches are reviewed. The patient gave verbal consent for participating in the surgical video. The video can be found here: https://stream.cadmore.media/r10.3171/2022.1.FOCVID21259.


Microbiological characterisation of Burkholderia cepacia isolates from cystic fibrosis patients: investigation of the exopolysaccharides produced.
Eleven strains of Burkholderia cepacia were isolated directly from clinical specimens: 10 from sputum of cystic fibrosis patients, and one from a vaginal swab. They were biochemically identified using API20NE and confirmed by a PCR-based assay. The genomovar characterisation obtained by specific PCR amplification revealed seven strains belonging to genomovar I, three belonging to genomovar IIIA and one belonging to genomovar IV. All isolates were also typed by ribotyping and random amplification of polymorphic DNA analysis. Some of the characterised strains were examined for the ability to produce exopolysaccharides, with the aim of correlating the genomovar with the exopolysaccharide structure. The polysaccharides were analysed by means of methylation analysis and 1H-NMR spectroscopy in order to determine structural similarities. It was shown that different strains are capable of producing chemically different polysaccharides.


Lysosomal acid proteinase of rabbit liver.
1. Acid proteinase from rabbit liver lysosomes was purified about 1000-fold, on a protein basis. 2. The purification procedure involved isolation of a lysosomal-mitochondrial pellet and conversion of this into an acetone-dried powder. 3. The enzyme was extracted with an acidic buffer and subjected to column chromatography with DEAE-Sephadex and Sephadex G-100. 4. The molecular weight of the enzyme was 50000-52000. 5. Maximal activity against haemoglobin was obtained at pH3.2; serum albumin was attacked, but very much more slowly. 6. Several possible inhibitors of the enzyme were tested. Thiol-blocking reagents, several inhibitors of trypsin and chymotrypsin, and a chelating agent were without effect. 7. The enzyme was competitively inhibited by 3-phenylpyruvic acid at low concentrations. 8. Dithiothreitol caused rapid inactivation of the enzyme at pH8. 9. It is concluded that this enzyme is a form of cathepsin D, which may be widely distributed in lysosomes.


Validity of motor impairment scale in long-term care insurance system of Korea.
To validate the Motor Impairment Scale (MIS) of the Korean long-term care insurance (LTCI) system by comparing with the service time offered for aiding activities of daily living (ADL) and the ADL score. A total of 407 elderly subjects without dementia who had used LTCI services were included in this study. Spearman correlations and multivariate linear regression models were employed to determine the relationship of the upper and lower limb MIS (U-MIS and L-MIS, respectively) to the service time and ADL. Stratified analyses for the facility group (n=121) and the domiciliary group (n=286) were performed. There were significant differences in characteristics between facility group and domiciliary group. The MIS was significantly correlated with service time in facility group (Spearman p=0.41 for U-MIS, Spearman p=0.40 for L-MIS). After adjusting for age, sex, and cognition score, U-MIS was an independent predictor for service time in facility group (p=0.04). In domiciliary group, no significant correlation was found between the MIS and service time. The MIS correlated with all of the ADL items and total ADL score in both groups. After adjusting for other factors including age, sex, and cognitive score, U-MIS and L-MIS were independent variables for explaining the total ADL score in both groups. The validity of the MIS as an evaluation tool in the physically-disabled elderly is higher in facility group than in domiciliary group. As an easy, objective, and simple method, MIS can be a useful tool in the LTCI system of Korea.


Health perception and restorative experience in the therapeutic landscape of urban wetland parks during the COVID-19 pandemic.
The effects of restoration and inspiration in the therapeutic landscape of natural environments on visitors during the COVID-19 pandemic have been well-documented. However, less attention has been paid to the heterogeneity of visitor perceptions of health and the potential impacts of experiences in wetland parks with green and blue spaces on visitors' overall perceived health. In this study, we investigate the impact of the restorative landscapes of wetland parks on visitors' health perceptions in the context of the COVID-19 pandemic. In our survey, 582 respondents participated in an online questionnaire. We analyzed the respondents' health perceptions in terms of latent class analysis, used multinomial logistic regression to determine the factors influencing the potential categorization of health perceptions, and used structural equation modeling to validate the relationships between health perceptions of different groups and landscape perceptions of wetland parks, restorative experiences, and personality optimistic tendencies. The results identified three latent classes of health perceptions. Gender, marital status, education, occupation, income, distance, frequency of activities, and intensity of activities were significant predictors of potential classes of perceived health impacts among wetland park visitors. This study revealed the nature and strength of the relationships between health perception and landscape perception, restorative experience, and dispositional optimism tendencies in wetland parks. These findings can be targeted not only to improve visitor health recovery but also to provide effective references and recommendations for wetland park design, planning, and management practices during and after an epidemic.


Breast-feeding and contraception in Peru.
This retrospective study examined duration of breast-feeding and concurrent contraceptive use among 5,648 Peruvian women. Data were gathered during 1986-1992 as part of the Demographic and Health Survey (DHS). The women gave birth to 7,951 infants, 95% of whom were breastfed; 44% of the mothers used contraception while breastfeeding. Consistent with the literature, mothers using oral contraception breastfed for significantly less time than those using other methods. Unexpectedly, mothers using periodic abstinence or withdrawal breastfed longer (15.5 and 15.3 months) than those using other methods or non-contraceptors. Among mothers changing contraceptive methods while breastfeeding the same child, those changing to abstinence and withdrawal breastfed longest (18 months). The relationship of duration of breast-feeding with contraceptive use remained after controlling for other predictors of duration of breast-feeding. Additional data are needed to explain this phenomenon in Peru and perhaps elsewhere.


Breast carcinoma with spontaneous regression after needle biopsy: a case report and literature review.
Spontaneous regression (SR) of cancer is a rare condition in which the cancer partially or completely disappears without treatment. We report a case of breast cancer with tumor regression and spontaneously induced T-cell-mediated immunological responses in a surgical specimen obtained after core needle biopsy (CNB). A 52-year-old woman presented with a mass in the right breast. Mammography showed a high-density mass with fine serrated margins in the right lower outer quadrant. Breast ultrasonography showed an irregular hypoechoic mass with a maximum diameter of 22 mm. CNB was performed and revealed an invasive ductal carcinoma with negative estrogen receptors, positive progesterone receptors, and negative HER2 (1+). The Ki67 index was 70% to 80%. Luminal B cT2N1M0 stage IIB right breast cancer was diagnosed. Although preoperative chemotherapy was considered, surgery was selected because of her history of schizophrenia. She underwent right mastectomy and axillary lymph node dissection. A postoperative pathological analysis revealed a 20 mm × 10 mm × 10 mm mass. However, most areas of the mass regressed and appeared as necrotic tissue with no obvious invasive areas. Only intraductal extension was observed in one glandular duct. Axillary lymph node metastases were not observed. These results suggest that the tumor may have spontaneously regressed, possibly because of the CNB procedure. Follow-up without treatment was performed, and no recurrence occurred during 2 years after surgery. Invasive ductal carcinoma may spontaneously regress after preoperative CNB.


Aziridine-Mediated Ligation at Phenylalanine and Tryptophan Sites.
An efficient approach towards peptide synthesis that allows easy access to variety of small peptides via one-pot aziridine-mediated ligation/desulfurization strategy has been described. The protocol afforded a library of phenylalanine- and tryptophan-containing α-peptides in good yields by regioselective ring-opening of aziridine-3-aryl-2-carboxylates with peptide thioacids, followed by desulfurization.


[Hepatitis B vaccination: the danger of AIDS transmission].
The safety of the hepatitis B vaccine H-B- Vax derives from a very strict screening of plasma donors as well as an extensive production process consisting of several purification and three inactivation steps. During a follow up of about 20 000 vaccine recipients over a 7 year-period, no known occurrence of AIDS or other infectious diseases have been associated with the vaccine. Also no known case of AIDS occurred in a group of 200 000 persons at low risk vaccinated since 1981. The hepatitis B vaccine is highly recommended to all people at high risk in Western Germany by the health organizations as well as the WHO.


The history of facial palsy and spasm: Hippocrates to Razi.
Although Sir Charles Bell was the first to provide the anatomic basis for the condition that bears his name, in recent years researchers have shown that other European physicians provided earlier clinical descriptions of peripheral cranial nerve 7 palsy. In this article, we describe the history of facial distortion by Greek, Roman, and Persian physicians, culminating in Razi's detailed description in al-Hawi. Razi distinguished facial muscle spasm from paralysis, distinguished central from peripheral lesions, gave the earliest description of loss of forehead wrinkling, and gave the earliest known description of bilateral facial palsy. In doing so, he accurately described the clinical hallmarks of a condition that we recognize as Bell palsy.


Patient-level and hospital-level variation and related time trends in COVID-19 case fatality rates during the first pandemic wave in England: multilevel modelling analysis of routine data.
A report suggesting large between-hospital variations in mortality after admission for COVID-19 in England attracted much media attention but used crude rates. We aimed to quantify these variations between hospitals and over time during England's first wave (March to July 2020) and assess available patient-level and hospital-level predictors to explain those variations. We used administrative data for England, augmented by hospital-level information. Admissions were extracted with COVID-19 codes. In-hospital death was the primary outcome. Risk-adjusted mortality ratios (standardised mortality ratios) and interhospital variation were calculated using multilevel logistic regression. Early-wave (March to April) and late-wave (May to July) periods were compared. 74 781 admissions had a primary diagnosis of COVID-19, with 21 984 in-hospital deaths (29.4%); the 30-day total mortality rate was 28.8%. The crude in-hospital death rate fell in all ages and overall from 32.9% in March to 13.4% in July. Patient-level predictors included age, male gender, non-white ethnic group (early period only) and several comorbidities (obesity early period only). The only significant hospital-level predictor was daily COVID-19 admissions in the late period; we did not find a relation with staff absences for COVID-19, mechanical ventilation bed occupancies, total bed occupancies or bed occupancies for COVID-19 admissions in either period. Just 4 (3%) and 2 (2%) hospitals were high, and 5 (4%) and 0 hospitals were low funnel plot mortality outliers at 3 SD for early and late periods, respectively, after risk adjustment. We found no strong correlation between early and late hospital-level mortality (r=0.17, p=0.06). There was modest variation in mortality following admission for COVID-19 between English hospitals after adjustment for risk and random variation, in marked contrast to early media reports. Early-period mortality did not predict late-period mortality.


What changes in health behaviour might nurses logically expect from their health education work?
This paper examines nurses' health education work from a philosophical perspective. Two key concepts, choice and autonomy, are explored by analysing examples of the health education work of the practice nurse and the health visitor. As a result, the question, 'what changes in health behaviour might nurses logically expect from their health education work?' is considered. The individualistic assumption within nurses' health education work, that individual patients and clients face certain choices and are able to exert some control over their health status, is reviewed. Choices related to healthy eating, for example, are recognized to be constrained by issues such as finance, time and social circumstances. The choice not to smoke is similarly constrained, for example, by social deprivation, cultural patterns and advertising. The paper both rejects an overly determined conception of patients and clients where they are viewed as unable to make any choices, but also cautions against the danger of victim-blaming. Constraints on patients' and clients' autonomy in health education by nurses are also considered. These limitations on health education work include, for example, a lack of scientific knowledge related to an individual's propensity to develop disease. In contrast, health education work within nursing may also be seen as enabling people to be more autonomous in relation to their health by imparting knowledge about health risks. Health education work by nurses thus emerges from the analysis as a constrained but valuable activity.


Up-Regulation of SIRT1 Reduces Endoplasmic Reticulum Stress and Renal Fibrosis.
Endoplasmic reticulum (ER) stress is emerging as an important factor in the development of organ fibrosis. Therefore, modulation of ER stress may serve as one of the possible therapeutic approaches to renal fibrosis. SIRT1, a class III histone deacetylase, has been found to exert beneficial effects in kidney diseases. However, it is largely unknown whether and how SIRT1 suppresses the ER stress. We postulated that upregulation of SIRT1 would suppress the ER stress through induction of heme oxygenase-1 (HO-1) and thioredoxin. HK-2 tubular cells, experimental mouse models of tunicamycin (TM)-induced ER stress and unilateral ureteral obstruction (UUO) were used. Expression of ER stress-induced protein was measured by Western blot analysis and immunohistochemical staining. ER stress was induced by chemical ER stress inducers [TM [,]thapsigargin (TG)] and non-chemical inducers such as angiotensin II, aldosterone, high glucose and albumin. SIRT1 activator (SRT1720) induced SIRT1 expression in a time- and dose-dependent manner in HK-2 cells. SRT1720 suppressed the TM- or TG-induced ER stress, as shown by inhibition of TM- or TG-induced upregulation of glucose-related protein 78 (GRP78), phosphor-specific eukaryotic translation initiation factor-2α and C/EBP homologous protein through HO-1 and thioredoxin, which were abolished by pretreatment with SIRT1 inhibitor (sirtinol). SRT1720 also suppressed the ER stress induced by angiotensin II, aldosterone, high glucose and albumin. In animal studies, treatment with SRT1720 reduced the tubular expression of GRP78 and increased the expression of HO-1 and thioredoxin. SRT1720 also reduced the UUO-induced renal fibrosis. SIRT1 may serve as a promising therapeutic target by reducing ER stress and fibrosis.


Redox-Active Tin Metal-Organic Framework with a Thiolate-Based Ligand.
Metal-organic frameworks (MOFs) and coordination polymers composed of thiolates as coordinating functional groups are interesting materials with unique optical and electronical properties. Herein, we report the preparation of KGF-4 and KGF-10, two Sn-MOF crystal structures with bonds between Sn and thiolate. KGF-10 was isolated as a pure phase and found to exhibit redox properties and a semiconducting band structure, as confirmed by first-principles (density functional theory) calculations.


Application of POLARIC™ fluorophores in an in vivo tumor model.
Fluorescent and luminescent tools are commonly used to study the dynamics of cancer progression and metastases in real-time. Fluorophores have become essential tools to study biological events. However, few can sustain fluorescence long enough during long-term studies. In the present study, we focused on a series of new amphiphilic fluorophores known as POLARIC™, which emit strong fluorescence in lipid bilayers and can be readily modified using the Suzuki-Miyaura cross-coupling reaction. Appropriate chemical modifications of substituent groups can improve target-site specificity, reduce cytotoxicity and prolong emission. Therefore, in contrast to conventional fluorescent probes, these fluorophores show promise for long-term monitoring of biological processes. In the present study, we conducted long-term observations of tumor growth and metastasis using a POLARIC derivative as a novel fluorescent probe. For this purpose, we studied the metastatic melanoma cell line A375-SM, which proliferates at a high rate. We compared the characteristics of the POLARIC probe with the commercially available fluorescent dye PKH26 and fluorescent protein mRFP1. A375-SM cells were labeled with these fluorescent probes and orthotopically implanted into nude mice. The fluorescence emitted by POLARIC was detected more than five weeks after implantation without causing detectable harmful effects on tumor growth. By contrast, fluorescence of cells labeled with PKH26 could not be detected at this same time. Furthermore, POLARIC-, but not PKH26-labeled cells, were also detected in lung metastases. These results indicate that labeling cells with POLARIC fluorophores can significantly extend the time course of in vivo studies on tumor cell growth.


Ultrastructural localization of nicotinamide adenine dinucleotide phosphatase (NADPase), thiamine pyrophosphatase (TPPase), and cytidine monophosphatase (CMPase) in the Golgi apparatus of early spermatids of the rat.
At the early steps 3-7 of spermiogenesis the hemispherical Golgi apparatus elaborates and is closely associated to the acrosomic system which grows at the surface of the spermatid's nucleus. It shows two distinct zones, a cortex made up of flattened saccules and related membranous tubules, and a medulla containing various types of vesicular profiles. The various components of the cortex of the Golgi apparatus were tested for their reactivity to three phosphatases. Nicotinamide adenine dinucleotide phosphatase activity (NADPase, Smith, 1980) was observed in the middle two to six saccules in the stack with a midsaccule being more reactive than the saccules above and below. A weak and spotty reaction was also noted in the remaining saccules on the trans-face of the stack and in the thick elements making up the GERL on the trans aspect of the stacks of saccules. Thiamine pyrophosphatase activity (TPPase, Novikoff and Goldfisher, 1961) was found in one or two saccules on the trans-face of the stacks but was absent from the other Golgi components. Cytidine monophosphatase activity (CMPase, Novikoff, 1967) was observed in the GERL, in vesicles of the medulla and in the developing acrosomic system. In the intersaccular regions of the cortex the branching membranous tubules showed the same reactivity for the phosphatases to that of the saccules to which they are connected. ER cisternae associated with the Golgi apparatus, anastomotic membranous tubules seen in the peripheral Golgi region, small vesicles, as well as the first saccule on the cis-face of the stacks were all negative for the three enzymes studied. These data indicated that in the cortex of the Golgi apparatus there were several distinct compartments that could be distinguished on the basis of structural and cytochemical features.


The IP3 R Binding Protein Released With Inositol 1,4,5-Trisphosphate Is Expressed in Rodent Reproductive Tissue and Spermatozoa.
Besides its capacity to inhibit the 1,4,5-trisphosphate (IP3) receptor, the regulatory protein IRBIT (IP3 receptor binding protein released with IP3) is also able to control the activity of numerous ion channels and electrolyte transporters and thereby creates an optimal electrolyte composition of various biological fluids. Since a reliable execution of spermatogenesis and sperm maturation critically depends on the establishment of an adequate microenvironment, the expression of IRBIT in male reproductive tissue was examined using immunohistochemical approaches combined with biochemical fractionation methods. The present study documents that IRBIT is expressed in Leydig and Sertoli cells. In addition, pronounced IRBIT expression was detected in sperm precursors during early stages of spermatogenesis as well as in spermatozoa. Analyzing tissue sections of rodent epididymides, IRBIT was found to co-localize with the proton pumping V-ATPase and the cystic fibrosis transmembrane conductance regulator (CFTR) at the apical surface of narrow and clear cells. A similar co-localization of IRBIT with CFTR was also observed for Sertoli cells and developing germ cells. Remarkably, assaying caudal sperm in immunogold electron microscopy, IRBIT was found to localize to the acrosomal cap and the flagellum as well as to the sperm nucleus; moreover, a prominent oligomerization was observed for spermatozoa. The pronounced occurrence of IRBIT in the male reproductive system and mature spermatozoa indicates a potential role for IRBIT in establishing the essential luminal environment for a faithful execution of spermatogenesis and epididymal sperm maturation, and suggest a participation of IRBIT during maturation steps after ejaculation and/or the final fertilization process.


A microparticle enzyme immunoassay to measure sirolimus.
Measurement of sirolimus as a guide to therapy is widely accepted. Since the commercial introduction of the drug, the only method available to measure blood concentrations has been high-performance liquid chromatography (HPLC). Only a limited number of centers have the facilities to perform this technique and, as a result, the measurement of the drug has been performed in central laboratories, often some distance from the clinical centers. This article describes a single-center assessment of a new immunoassay to measure sirolimus, including a comparison between immunoassay results and a chromatographic technique. Calibration accuracy was good, reproducibility at 11 ng/mL was better than 6%, and sensitivity was better than 2 ng/mL; all these parameters are appropriate for routine clinical use. There was a mean positive bias of almost 20% for the measurement of sirolimus in clinical samples from kidney transplant patients receiving the drug, compared with HPLC. This bias was most likely due to cross-reactivity with metabolites of the drug and was of the order noted when an earlier configuration of this immunoassay was used in clinical practice. We conclude that, despite the analytical bias, this immunoassay offers a viable alternative to the use of HPLC and would be an assay suitable for implementing at local centers.


Ultrastructural immunocytochemical localization of substance P in the cat small intestine.
The immunocytochemical peroxidase-antiperoxidase technique was used to identify substance P (SP) in the cat small intestine at the ultrastructural level in the nerve plexuses. In the myenteric plexus the SP containing fibres form synapses with the other nerve terminals and run parallel to the circular muscle. The SP in these fibres is present in the vesicles of 80 to 120 nm or 150 to 250 nm in diameter. The results support the contention that SP containing nerve terminals are present in the enteric nervous system.


Trials in isolated systolic hypertension: an update.
Isolated systolic hypertension (ISH) has proved to be a powerful predisposing factor for cardiovascular diseases in the elderly. Recent placebo-controlled interventional trials such as the Systolic Hypertension in the Elderly Program, the Systolic Hypertension in Europe, and the Systolic Hypertension in China showed that the lowering of systolic blood pressure using a diuretic- or a calcium antagonist-based treatment is associated with a decrease in cardiovascular events. Antihypertensive therapy was found especially effective in preventing stroke in the elderly with ISH. A slowing in the progression of dementia was observed in patients randomized to a calcium antagonist-based treatment. Patients at high cardiovascular risk such as those with diabetes benefited the most from treatment. In another trial performed in patients with left ventricular hypertrophy (Losartan Intervention For Endpoint Reduction), a subset of patients had ISH. In those patients, an angiotensin II antagonist-based treatment was superior to a b-blocker-based treatment in preventing cardiovascular complications. The experience accumulated in patients with ISH showed that combination therapy is often required to control blood pressure. Overall, the evidence available today indicates that pharmacologic treatment of ISH markedly improves the outcome of elderly patients.


Sensitivity of human ovarian carcinoma cells to interferon and other antitumor agents as assessed by an in vitro semi-solid agar technique.
To determine the sensitivity in vitro of human ovarian carcinoma cells to the antiproliferative effects of human leukocyte interferon, 18 samples of ascitic fluid from 15 affected patients were cultured in semi-solid agar by the technique of Hamburger and Salmon. Cultures were examined at weekly intervals after initiation and the number and size of each tumor colony recorded. Growth as defined by increase in total tumor colony number with time was obtained in 45% of the samples, or 53% of the patients, or 67% of the ascitic fluid samples with tumor cells demonstrated by Pap smear. No growth occurred in samples from recently treated patients or in samples devoid of tumor cells as assessed by Pap smear. Response to interferon directly incorporated into the agar culture system or preincubated with cells prior to their inclusion in culture was defined as reduction in total colony number by greater than or equal to 50% and partial response by greater than or equal to 25% reduction. The response rate for samples, The nontreated controls of which showed evidence of growth, was 71%, and that of samples that contained tumor colonies with no increase in growth during the culture period was 75%. Sensitivity to interferon was not related to the histology or grade of the tumor or to the stage of the disease. In general the responsiveness of the tumor cells to interferon ran parallel to the overall responsiveness to a variety of other chemotherapeutic agents. As this culture system has been proven by other investigators to be predictive of in vivo resistance to antitumor drugs with considerable accuracy and also to be predictive of in vivo response to a lesser degree, it will be important to determine whether similar relationships between in vitro and in vivo sensitivity obtain for interferon.


[Persistent sinusoids of the left chamber wall].
Angiographic pictures of persistent sinusoids of the left chamber wall are presented. The clinical significance of this very rare phenomen is not clear yet.


STRUCTURE OF TYPE 5 ADENOVIRUS. I. ANTIGENIC RELATIONSHIP OF VIRUS-STRUCTURAL PROTEINS TO VIRUS-SPECIFIC SOLUBLE ANTIGENS FROM INFECTED CELLS.
Type 5 adenovirus was purified by fluorocarbon (freon 113) treatment followed by banding in a CsCl equilibrium density gradient. This method permitted separation of virus from normal host cell materials and virus-specific soluble antigens. Virus banded in CsCl with a mean bouyant density of 1.3349 gm/cm(3). The three virus-specific soluble antigens (group- and type-specific antigens and toxin) banded together with a mean bouyant density of 1.2832 gm/cm(3). The group-specific antigen was the predominant antigen of the purified virus particle, whereas the group- and type-specific antigens were present in equal titers in the antigen band. Infectious virus particles were inactivated by prolonged dialysis at pH 10.5. Centrifugation of inactivated virus preparations in a CsCl equilibrium density gradient resulted in separation of virus DNA from specific antigen: the antigens banded with a mean bouyant density of 1.2832 gm/cm(3) and the DNA sedimented to the bottom of the tube. The predominant antigen derived from purified virus particles was the group-specific antigen and it was in the same relative proportion to the type-specific antigen as measured in intact particles. The antigens derived from disrupted virus were immunologically identical with the soluble virus antigens present in infected cells.


Identification of putative unique immunogenic ZIKV and DENV1-4 peptides for diagnostic cellular based tests.
Since the re-emergence of Zika virus in 2014 and subsequent association with microcephaly, much work has focused on the development of a vaccine to halt its spread throughout the world. The mosquito vector that transmits this virus is widespread and responsible for the spread of other arboviridae including Dengue. Current diagnostic methods rely on serologic testing that are complicated by cross reactivity and therefore unable to distinguish Zika from Dengue infection in the absence of virus isolation. We performed an in silico analysis to identify potential epitopes that may stimulate a unique T-lymphocyte response to distinguish prior infection with Zika or Dengue. From this analysis, we not only identified epitopes unique to Zika and Dengue, but also identified epitopes unique to each Dengue serotype. These peptides contribute to a pool of peptides identified for vaccine development that can be tested in vitro to confirm immunogenicity, absence of homology and global population coverage. The current lack of accurate diagnostic testing hampers our ability to understand the scope of the epidemic, implications for vaccine implementation and complications related to monoinfection and co-infection with these two closely related viruses.


Early genetic diagnosis of clarithromycin resistance in Helicobacter pylori.
The drug resistance rate of clinical Helicobacter pylori (H. pylori) isolates has increased. However, the mechanism of drug resistance remains unclear. In this study, drug-resistant H. pylori strains were isolated from different areas and different populations of Chinese for genomic analysis. To investigate drug-resistant genes in H. pylori and find the genes for the early diagnosis of clarithromycin resistance. Three drug-resistant H. pylori strains were isolated from patients with gastritis in Bama County, China. Minimal inhibitory concentrations of clarithromycin, metronidazole, and levofloxacin were determined and complete genome sequencing was performed with annotation. Hp1181 and hp1184 genes were found in these strains and then detected by reverse transcription polymerase chain reaction. The relationships between hp1181 or hp1184 and clarithromycin resistance were ascertained with gene mutant and drug-resistant strains. The homology of the strains with hp26695 was assessed through complete genome detection and identification. Differences in genome sequences, gene quantity, and gene characteristics were detected amongst the three strains. Prediction and analysis of the function of drug-resistant genes indicated that the RNA expression of hp1181 and hp1184 increased in the three strains, which was the same in the artificially induced clarithromycin-resistant bacteria. After gene knockout, the drug sensitivity of the strains was assessed. The strains showing a high degree of homology with hp26695, hp1181, and hp1184 genes were found in these strains; the expression of the genes hp1184 and hp1181 was associated with clarithromycin resistance. Hp1181 and hp1184 mutations may be the earliest and most persistent response to clarithromycin resistance, and they may be the potential target genes for the diagnosis, prevention, and treatment of clarithromycin resistance.


Corrected Lymphocyte Percentages Reduce the Differences in Absolute CD4+ T Lymphocyte Counts between Dual-Platform and Single-Platform Flow Cytometric Approaches.
To determine whether a corrected lymphocyte percentage could reduce bias in the absolute cluster of differentiation (CD)4+ T lymphocyte counts obtained via dual-platform (DP) vs standard single-platform (SP) flow cytometry. The correction factor (CF) for the lymphocyte percentages was calculated at 6 laboratories. The absolute CD4+ T lymphocyte counts in 300 blood specimens infected with human immunodeficiency virus (HIV) were determined using the DP and SP methods. Applying the CFs revealed that 4 sites showed a decrease in the mean bias of absolute CD4+ T lymphocyte counts determined via DP vs standard SP (-109 vs -84 cells/μL, -80 vs -58 cells/μL, -52 vs -45 cells/μL, and -32 vs 1 cells/μL). However, 2 participating laboratories revealed an increase in the difference of the mean bias (-42 vs -49 cells/μL and -20 vs -69 cells/μL). Use of the corrected lymphocyte percentage shows potential for decreasing the difference in CD4 counts between DP and the standard SP method.


Construction of eukaryotic expression plasmid human transforming growth factor beta3 and its transfection into precartilaginous stem cells.
To obtain seed cells for cartilage repair through constructing recombinant human transforming growth factor beta3 vector (hTGF-beta3) and transfecting it into rat's precartilaginous stem cells (PSCs). Gene engineering technique was introduced to construct eukaryotic expression plasmid pcDNA3.1 (+)-hTGF-beta3. PSCs of rats were isolated and purified with method of immunomagnetic microbeads. Then PSCs were cotransfected with plasmid hTGF-beta3 and pcDNA3.1 (+)-enhanced green fluorescence protein (EGFP) by liner polyethyleneimine (PEI). And 48 hours later the transient expression of EGFP was observed under a fluorescence microscope, and the expression of hTGF-beta3 was detected with reverse transcription-polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA). The sequences of the recombinants were consistent with that from Genebank. Cotransfection of EGFP provided fast visual confirmation of successful transduction. The hTGF-beta3 mRNA and protein expression could be detected by RT-PCR and ELISA. The recombinant plasmid is correctly constructed and successfully transfected into rat's PSCs, which is an important step to treat epiphyseal injury or other osteo-cartilage diseases with transgenic therapy.


Melanoma of the scalp: an underdiagnosed malignancy?
We report a case of scalp melanoma that was found incidentally after the patient complained of pruritic lesions on his scalp. The melanoma was 13 mm in diameter and had a Breslow thickness of 0.25 mm. The incidence of melanoma has been on the rise, with a high incidence occurring in men on the head, neck, and trunk. This case stresses the need to thoroughly examine the entire scalp when performing total body screening examinations for skin cancer.


Rasch analysis of the UK Functional Assessment Measure in a sample of patients with traumatic brain injury from the UK national clinical database.
To determine whether the UK Functional Assessment Measure (UK FIM+FAM) fits the Rasch model in patients with complex disability following traumatic brain injury. Psychometric evaluation including preliminary exploratory and confirmatory factor analyses followed by Rasch analysis. A multicentre UK national cohort of 1,956 patients admitted for specialist rehabilitation following traumatic brain injury. The suitability of the Partial Credit Model was confirmed by the likelihood-ratio test (χ2 (df86) =7,325.0, p < 0.001). Exploratory and confirmatory factor analyses supported 3 factors (Motor, Communication, Psychosocial). Rasch analysis of the full scale incorporating the 3 factors as super-items resulted in an acceptable overall model fit (χ2 (df24)=36.72, p = 0.05) and strict uni-dimensionality when tested on a sub-sample of n = 320. These results were replicated in a full sample (n = 1,956) showing uni-dimensionality and good reliability with Person Separation Index = 0.81, but item trait interaction was significant due to the large sample size. No significant differential item functioning was observed for any personal factors. Neither uniform re-scoring of items nor exclusion of participants with extreme scores improved the model fit. The UK FIM+FAM scale satisfies the Rasch model reasonably in traumatic brain injury. A conversion table was produced, but its usefulness in clinical practice requires further exploration and clinical translation.


Measuring hip flexor and extensor strengths across various postures using a fixed belt.
[Purpose] The purpose of this study was to evaluate hip flexor and extensor strength due to differences in posture measurement. [Subjects and Methods] Healthy adults (26 males and 24 females) were enrolled. Using a hand-held dynamometer, hip flexor and extensor strengths were measured in various postures and in a basic posture (sitting posture and hip/knee joint flexed 90°) according to the Manual Muscle Testing procedure. While calculating intraclass correlation coefficients by measurement, hip flexor and extensor strengths were compared in males and females for every posture. [Results] Intraclass correlation coefficients were greater than 0.7 in every measurement. There was no significant difference in hip flexor and extensor strengths in both males and females. Furthermore, there was a significant difference in right and left hip flexor strengths and in left hip extensor strength. [Conclusion] Hip flexor and extensor strengths can be simply and easily measured using a hand-held dynamometer.


Fetal compensatory responses to reduced oxygen delivery.
I have described how various maternal and fetal conditions can affect fetal oxygen delivery. It is clear from much of the recent experimental evidence that fetal oxidative metabolism can be sustained despite reductions in fetal O2 delivery of 40-50%. As long as fetal oxygen reserves are not depleted, fetal metabolic functions will continue aerobically, even though fetal hypoxemia is present. As O2 reserves are exhausted in some tissues, fetal hypoxemia will be associated with tissue hypoxia, the net result of which will be anaerobic metabolism, lactic acidosis, and tissue death. Whether a fetus is adequately oxygenated or not is a function of the quantity of oxygen reserve available. A fetus with a substantial oxygen reserve can compensate fully for most interferences in its oxygen supply and can maintain oxidative metabolism under a variety of conditions. In contrast, a fetus with minimal oxygen reserves will not tolerate even the mildest degree of O2 deficiency without developing tissue hypoxia or even death in utero. The quantity of O2 delivered to the fetus, rather than the specific condition that may be adversely affecting O2 delivery, is the important determinant of the adequacy of fetal oxygenation.


Impregnation of mesoporous silica with poor aqueous soluble molecule using pressurized carbon dioxide: Is the solubility in the supercritical and subcritical phase a critical parameter?
Recently, mesoporous silica (MS) has been used as a material able to maintain amorphous state of active compounds and therefore, enhance the oral bioavailability of BCSII drugs. Among impregnation methods of MS, techniques using supercritical carbon dioxide (Sc-CO2) are promising tools. Solubility of compounds in Sc-CO2 is reported as one of the most critical parameters, which usually limits its use in drug formulation. Indeed, most of compounds have poor solubility in Sc-CO2. The aim of this work is to compare different MS and to study alternative processes using pressurized CO2 for insoluble molecule in Sc-CO2. By using high pressure reactor, DSC, HPLC and in vitro dissolution tests, the crystallinity and dissolution profiles of MS with different pore size (6.6 nm, 25.0 nm and 2.5 nm) impregnated with fenofibrate (FF) under Sc-CO2 were compared to select the most appropriate carrier. Then, the selected MS has been impregnated under supercritical, subcritical and atmospheric conditions. We have shown that the MS pore size of 6.6 nm provides the higher amorphous drug loading capacity as well as the faster and higher drug dissolution. In addition, FF-MS formulations produced with pressurized CO2 as fusion medium, both in subcritical and supercritical conditions; give similar crystallinity and dissolution results compared to those produced with supercritical fluids as solvent. Through this study, we show new possibilities of using CO2 for insoluble compounds in this fluid.


Immunocamouflage: prevention of transfusion-induced graft-versus-host disease via polymer grafting of donor cells.
Graft-versus-host disease (GVHD) can occur following the transfer of allogeneic lymphocytes into immunosuppressed and, in rare cases, immunocompetent recipients. The initiation of GVHD requires the allorecognition of the recipient's disparate MHC molecules by the donor T lymphocytes (T cell). Currently, GVHD is controlled by cyclosporine administration--a potent, but toxic, T-cell suppressing agent. To determine if the nontoxic grafting of methoxypoly(ethylene glycol) (mPEG) to immunologically foreign lymphocytes could prevent allorecognition and GVHD, in vitro and in vivo murine studies were performed. In vitro studies utilizing mixed lymphocyte reactions (MLRs) demonstrate that mPEG modification effectively prevented allorecognition and subsequent T-cell proliferation. The loss of cellular proliferation was not due to mPEG cytotoxicity but rather to the inhibition of cell-cell interactions. Flow cytometric studies showed that T-cell and antigen-presenting cell adhesion molecules (CD2, CD11a), signaling (CD3epsilon, T-cell receptor), and costimulatory molecules (CD28, CD80) were efficiently immunocamouflaged by mPEG derivatization. Interestingly, upon antigenic stimulation mPEG-modified cells demonstrate enhanced apoptosis as evidenced by DNA laddering. In vivo studies using immunocompetent and immunosuppressed mice established that mPEG modification of donor lymphocytes effectively attenuated the in vivo proliferation of donor cells and the initiation of GVHD.


In vitro and in vivo stability investigations of Cu(II), Zn(II), Ca(II) and Gd(III) complexes with N,N'-bis(2-hydroxyiminopropionyl) propane-1,3-diamine.
Formation constants of copper(II), zinc(II), calcium(II) and gadolinium(III) with N,N'-bis(2-hydroxyiminopropionyl) propane-1,3-diamine (L2) have been studied at 25 degrees C and an ionic strength of 0.15 mol dm(-3). The reasonably high formation constants of the copper with this ligand are due to the ease with which the metal ion deprotonates the amide moieties. The square-planar coordination of L2 towards copper as predicted from UV-visible data may also account for the high selectivity of L2 towards the metal ion. Octanol/water partition coefficients of Cu(II)-L2 complexes indicate that although these complexes are largely hydrophilic, approximately 1.86% of the [CuL2H(-1)] species goes into the octanol layer and hence may promote dermal absorption of copper with a calculated penetration rate of 1.24 x 10(-5) cm h(-1). The [CuL2H(-1)] complex which predominates at pH 7.4 is a poor mimic of native copper-zinc superoxide dismutase. Blood-plasma simulation studies predict that, despite the high concentration of zinc and calcium in vivo, L2 is able to increase the low-molecular-mass fraction of copper. Biodistribution experiments using 64Cu-labelled [CuL2H(-1)] indicate an initial high uptake of this species in the liver, but it is predominantly excreted through the renal system.


Animal Models in the Pathophysiology of Cystic Fibrosis.
Our understanding of the multiorgan pathology of cystic fibrosis (CF) has improved impressively during the last decades, but we still lack a full comprehension of the disease progression. Animal models have greatly contributed to the elucidation of specific mechanisms involved in CF pathophysiology and the development of new therapies. Soon after the cloning of the CF transmembrane conductance regulator (CFTR) gene in 1989, the first mouse model was generated and this model has dominated in vivo CF research ever since. Nonetheless, the failure of murine models to mirror human disease severity in the pancreas and lung has led to the generation of larger animal models such as pigs and ferrets. The following review presents and discusses data from the current animal models used in CF research.


Morbidity control of schistosomiasis by mass drug administration: how can we do it best and what will it take to move on to elimination?
The World Health Organization (WHO) has, for some time, encouraged countries endemic for schistosomiasis to control morbidity from this disease through mass drug administration (MDA) of the well-tolerated drug, praziquantel (PZQ). With the London Declaration in January 2012 and the promise by Merck Serono to eventually donate 250 million PZQ tablets per year, most endemic countries in sub-Saharan Africa have now developed national plans to do MDA for schistosomiasis morbidity control. More recently, based on two World Health Assembly (WHA) resolutions (WHA 54.19 & WHA 65.21) on schistosomiasis, countries are further encouraged to eliminate schistosomiasis, where feasible. The fight against schistosomiasis is therefore in a critical period of tremendous opportunities and equal challenges. How do we do the most effective job of MDA? What tools do we need to do this job better? How will we know when to move from morbidity control to elimination? What combinations of interventions, beyond MDA, are needed to eliminate transmission? The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) has its Secretariat at the University of Georgia and with programs in more than 26 institutions in 19 countries it is trying to answer these very practical questions through multiple large field-based studies and the evaluation or development of better diagnostics for schistosomiasis. This presentation will summarize the current status of morbidity control and elimination programs and the operational research by SCORE that we hope will provide much-needed answers for national program managers so they can most effectively pursue these critical public health programs.


ACPI Conjugated Gold Nanorods as Nanoplatform for Dual Image Guided Activatable Photodynamic and Photothermal Combined Therapy In Vivo.
The nanoplatform GNR-ACPP-PpIX (designated as GNR-ACPI) is designed for dual image guided combined activatable photodynamic therapy (PDT) and photothermal therapy (PTT). In GNR-ACPI, gold nanorods (GNRs) are modified with a protoporphyrin (PpIX, a PDT agent) conjugated activatable cell penetrating peptide (ACPP), which consists of the matrix metalloproteinases-2 (MMP-2) sensitive peptide sequence GPLGLAG. First, the photoactivity of PpIX is effectively quenched by GNRs due to the strong near infrared region light absorption of GNR and the special "U type" structure of ACPP induced close contact between PpIX and GNR. However, once arriving at the tumor site, the GPLGLAG sequence is hydrolyzed by the MMP-2 overexpressed by tumor cells, resulting in the release of the residual cell membrane penetrating peptide (CPP) attached PpIX (CPP-PpIX) with the recovery of photoactivity of PpIX. In addition, with the help of CPP, more efficient cellular uptake of PpIX by tumor cells can be achieved, which will greatly improve the PDT efficacy. Moreover, the GNR can also be utilized for photothermic imaging as well as PTT for tumors. It is found that the combination of PTT and PDT under the guidance of dual-mode imaging greatly enhances the antitumor effects, while possessing negligible systematic toxicity.


A comparative study of fatty acid profile and formation of biofilm in Geobacillus gargensis exposed to variable abiotic stress.
Understanding bacterial fatty acid (FA) profile has a great taxonomic significance as well as clinical importance for diagnosis issues. Both the composition and nature of membrane FAs change under different nutritional, biotic and (or) abiotic stresses, and environmental stress. Bacteria produce both odd-carbon as well as branched-chain fatty acids (BCFAs). This study was designed to examine the effect of abiotic pressure, including salinity, temperature, pH, and oxinic stress on the growth, development, and FA profile in thermophilic Geobacillus gargensis. Under these stresses, 3 parametric ratios, 2-methyl fatty acids/3-methyl fatty acids (iso-/anteiso-FAs), BCFAs/straight-chain saturated fatty acids (SCSFA), and SCSFAs/straight-chain unsaturated fatty acids (SCUFA), in addition to total lipids affected by variable stresses were measured. Our results indicate that the ratio of total iso-/anteiso-FAs increased at the acidic pH range of 4.1-5.2 and decreased with increasing pH. The reverse was true for salt stress when iso-/anteiso-FAs ratio increased with salt concentration. The BCFAs/SCSFAs and SCSFAs/SCUFAs ratios increased at neutral and alkaline pH and high salt concentration, reduced incubation time, and comparatively high temperature (55-65 °C) of the growth medium. The bacterial total lipid percentage deceased with increasing salt concentration, incubation period, but it increased with temperature. The formation of extracellular polymeric substances was observed under all stress conditions and with the addition of sodium dodecyl sulfate (2 and 5 mmol/L) to the growth medium. The membrane phospholipid composition of the bacterium was analyzed by thin-layer chromatography.


Ag(I) and Cu(II) discrete and polymeric complexes based on single- and double-armed oxadiazole-bridging organic clips.
Four new oxadiazole-bridging ligands (L1-L4) were designed and synthesized by the reaction of 2,5-bis(2-hydroxyphenyl)-1,3,4-oxadiazole with isonicotinoyl chloride and nicotinoyl chloride, respectively. L1 and L3 are unsymmetric single-armed ligands (4- or 3-pyridinecarboxylate arm), and L2 and L4 are symmetric double-armed ligands (4- or 3-pyridinecarboxylate arms). Nine new complexes, [Ag(L1)]PF6.CH3OH (1), [Ag(L1)]ClO4.CH3OH (2), Cu(L2)(NO3)2.2(CH2Cl2) (3), [Cu(L2)2](ClO4)2.2(CH2CCl2) (4), Cu(L2)Cl2 (5), [Cu4(L3)2(H2O)2](L3)4(ClO4)4 (6), [Ag(L4)(C2H5OH)]ClO4 (7), [Ag(L4)(C2H5OH)]BF4 (8), and [Ag(L4)(CH3OH)]SO3CF3 (9), were isolated from the solution reactions based on these four new ligands, respectively. L1, L2, and L3 act as convergent ligands and bind metal ions into discrete molecular complexes. In contrast, L4 exhibits a divergent spacer to link metal ions into one-dimensional coordination polymers. New coordination compounds were fully characterized by infrared spectroscopy, elemental analysis, and single-crystal X-ray diffraction. In addition, the luminescent and electrical conductive properties of these new compounds were investigated.


[INTERACTION OF LACTOBACILLUS PLANTARUM 337D UKM B-2627 STRAIN CELLS WITH CLAY MINERALS IN VITRO].
To characterize the interaction of Lactobacillus plantaruni 337D UKM B-2627 strain, which has probiotic properties, with kaolinite and montmorillonite. The methods of infrared spectroscopy, transmission electron microscopy, the adsorption-structural static volumetric method, microbiological and statistical methods were used. The characteristics of the porous space of clay mineral particles were practically did not change compared with initial samples during the interaction with L. plantarum 337D UKM B-2627 strain cells, pore size distribution had become wider due to the emergence of large diameter pores, reduced surface area, but the adsorption capacity and the layered structure of clay minerals preserved. For the first time the ef- fect of kaolinite and montmorillonite on growth of L. plantaruni 337D strain in vitro was studied. The greatest stimulating effect of clay minerals was observed within two hours of cultivation. The specific growth rate of L. plantaruni 337D strain was in 5.2 times higher when cultured in MRS medium with 4 % of kaolinite and 6 times more - in MRS medium with 1 % montmorillonite versus control. The presence in the medium of kaolinite or montmorillonite slowed the process of reducing pH during growth of the L. plantarum 337D strain, compared with the control. In the presence of montmorillonite pH decreased more slowly than in the presence of kaolinite. The difference between initial pH value of medium with 4 % kaolinite and after two h (ApH) was 10 times less in comparison with the control. At the same time, pH of the medium with 1 % or 4 % montmorillonite began to decrease after 4 hours of cultivation. Different effect on the growth of L. plantarum 337D strain due to differences of physical and chemical characteristics of kaolinite and montmorillonite used in the study.


Tuberculosis Progression Does Not Necessarily Equate with a Failure of Immune Control.
Despite the obvious impact of tuberculosis on global health, there is currently no effective vaccine and there is increasing resistance against established front-line drug regiments. Our current understanding of disease progression in tuberculosis is shaped by data collected from the failure of immune control. We feel that this represents a biased approach, which constrains our capacity to understand both disease control and progression. In this opinion piece, we re-examine these questions in the context of recently published data from fluorescent bacterial reporter strains and the analysis of the different macrophage lineages present at sites of infection. We believe that this analysis provides alternative models for disease progression, which are not addressed through current vaccine or immune-therapeutic strategies.


An LC-MS Assay to Measure Superoxide Radicals and Hydrogen Peroxide in the Blood System.
Red blood cells are constantly exposed to reactive species under physiological or pathological conditions or during administration of xenobiotics. Regardless of the source, its accurate quantification is paramount in the area of theragnostics, which had been elusive up until now. Even if there are a lot of approaches to evaluate the oxidative stress, very sensitive methods are missing for the blood system. We therefore sought to apply a highly sensitive approach, by liquid chromatography coupled to mass spectrometry (UPLC-MS), for the quantification of reactive species such as superoxide radical and hydrogen peroxide using dihydroethidium (DHE) and coumarin boronic acid (CBA) probes respectively through the detection of 2-hydroxyethidium (2OH-E+) and 7-hydroxycoumarin (COH). The use of the high-resolution mass spectrometry associated to UPLC ensured a selective detection of superoxide and hydrogen peroxide in the blood system under diverse conditions such as oxidized red blood cells (RBCs), untreated and treated parasitized RBCs. Moreover, this technique allowed the determination of reactive species in human plasma. This protocol provides a huge opportunity for in-depth study of several pathological conditions vis-a-vis their treatment in modern medicine.


Fingolimod Affects Transcription of Genes Encoding Enzymes of Ceramide Metabolism in Animal Model of Alzheimer's Disease.
The imbalance in sphingolipid signaling may be critically linked to the upstream events in the neurodegenerative cascade of Alzheimer's disease (AD). We analyzed the influence of mutant (V717I) amyloid β precursor protein (AβPP) transgene on sphingolipid metabolism enzymes in mouse hippocampus. At 3 months of age AβPP/Aβ presence upregulated enzymes of ceramide turnover on the salvage pathway: ceramide synthases (CERS2, CERS4, CERS6) and also ceramidase ACER3. At 6 months, only CERS6 was elevated, and no ceramide synthase was increased at 12 months. However, sphingomyelin synthases, which utilize ceramide on the sphingomyelinase pathway, were reduced (SGMS1 at 12 and SGMS2 at 6 months). mRNAs for sphingomyelin synthases SGMS1 and SGMS2 were also significantly downregulated in human AD hippocampus and neocortex when compared with age-matched controls. Our findings suggest early-phase deregulation of sphingolipid homeostasis in favor of ceramide signaling. Fingolimod (FTY720), a modulator of sphingosine-1-phosphate receptors countered the AβPP-dependent upregulation of hippocampal ceramide synthase CERS2 at 3 months. Moreover, at 12 months, FTY720 increased enzymes of ceramide-sphingosine turnover: CERS4, ASAH1, and ACER3. We also observed influence of fingolimod on the expression of the sphingomyelinase pathway enzymes. FTY720 counteracted the AβPP-linked reduction of sphingomyelin synthases SGMS1/2 (at 12 and 6 months, respectively) and led to elevation of sphingomyelinase SMPD2 (at 6 and 12 months). Therefore, our results demonstrate potentially beneficial, age-specific effects of fingolimod on transcription of sphingolipid metabolism enzymes in an animal model of AD.


Monitoring the respiratory system of the mechanically ventilated patient.
Bedside monitoring of respiratory status is designed to measure specific parameters and alert the clinician when these parameters exceed the limits of a desired range. Parameters should include measures of respiratory mechanics, oxygenation, and ventilation. Monitoring is the only form of communication between the physician and a patient receiving neuromuscular blocking agents. Airway pressure tracing alone, or in conjunction with concurrent flow, measures respiratory system mechanics, resistance, compliance, and the work of breathing. Pulse oximetry reflects oxygenation, while mixed venous oximetry indicates the balance between oxygen supply and demand. Capnography is a noninvasive way of assessing ventilation. Taken as a whole, noninvasive monitoring provides useful information, reflecting trends in oxygenation, ventilation, and mechanics. This article reviews the concepts of noninvasive monitoring of critically ill patients. Emphasis is given to the patient receiving neuromuscular blocking agents.


A case series in individuals with multiple sclerosis using direct current electrical stimulation to inhibit spasticity and improve functional outcomes.
Multiple sclerosis (MS) has a high incidence of debilitating spasticity. Central Nervous System (CNS) intrafusal settings have an impact on spasticity level. Mechanoreceptors of the Peripheral Nervous System (PNS) communicate monosynaptically with the central nervous system (CNS). This case series assesses feasibility of multimodal treatment of individuals with MS using a direct current electrical stimulation (DC) to influence mechanoreceptors. Seven MS diagnosed participants with Expanded Disability Status Scale (EDSS) = 6.0-8.0 completed 18 visits over 6 weeks of using DC combined with neuromuscular reeducation. Design included pre-, post- outcome measures of EDSS, 12-item MS Walking Scale (MSWS-12), Range of Motion (ROM), Manual Muscle Testing (MMT), Modified Ashworth Test (MAT), Timed 25-Foot walk (T25WT), Timed Up and Go (TUG) and the Multiple Sclerosis Impact Scale-29 (MSIS-29). 125 out of a possible 126 visits were completed, demonstrating a high level of tolerance. Individual results included trends towards improvement in spasticity and agonists. This case series design of seven heterogenous subjects with MS is a low sample size for statistical analysis and should be considered a pilot. The study demonstrates a high level of feasibility and possible correlations to consider. Further research is warranted.


Factors of importance for return to work, experienced by patients with chronic pain that have completed a multimodal rehabilitation program - a focus group study.
To reduce the individual, societal, and economic burden of the high sick leave rates due to chronic pain, it is essential to find effective strategies for increasing return to work (RTW). Although multimodal rehabilitation programs (MMRPs) may have positive effects on RTW, the results are inconsistent. This study explores the factors that contribute to decreasing sick leave and increasing RTW in patients with chronic pain who completed a MMRP. Four focus groups and three individual interviews were conducted. In total, 18 patients were interviewed. All patients had chronic pain and had completed a MMRP. They were either employed or unemployed, either working to some degree or fully on sick leave. The data were analysed using qualitative content analysis. Three main categories were identified: Knowledge and understanding-prerequisites for tailored solutions; Individual adaptations-necessary but difficult to implement; and Stakeholder collaboration-needs improvement. The participants described a variety of facilitating and limiting factors that created complex prerequisites for RTW. This finding makes it clear that these patients need tailored interventions and strong collaboration among all stakeholders throughout the rehabilitation process. Tailored interventions and collaborations could improve the effectiveness of MMRPs.IMPLICATIONS FOR REHABILITATIONPatients with chronic pain need tailored solutions and adaptations based on their individual needs in the RTW rehabilitation process.To return to work, patients with chronic pain needs support to strengthen their selfconfidence and to be prepared with knowledge and strategies about their abilities and their rights and obligations in relation to the labour market.A well-designed and communicated RTW rehabilitation plan supports the patient in the RTW rehabilitation process.To improve the possibility for employees and employers to create a sustainable work situation, stakeholder reconciliation meetings should be held routinely over time to strengthen the transfer of knowledge and collaboration.


Consequences of phosphate imbalance.
Phosphorus is the sixth most abundant element in the body after oxygen, hydrogen, carbon, nitrogen, and calcium. It comprises about 1% of the total body weight of humans. Eighty-five percent of it is stored in the bone in the form of hydroxyapatite crystal; 14% is in the soft tissues in the form of energy-storing bonds with nucleotides (ATP, GTP), nucleic acids in chromosomes and ribosomes, 2,3-DPG in the red blood cells, and phospholipids in the cells' membranes. Less than 1% is in the extracellular fluids. Phosphate balance is maintained by multiple systems. The gut is responsible for the absorption of two thirds of the 4-30 mg/kg/day of phosphate intake. Absorption sites are all along the gut; in humans the most active site is the jejunum. The kidney filters 90% of the plasma phosphate and reabsorbs it in the tubuli. In states of hypophosphatemia the kidney can reabsorb the filtered phosphates very efficiently, reducing the amount excreted in the urine virtually to zero. The healthy kidney can excrete high loads of phosphate and rid the body of phosphate overload. Through the vitamin D-PTH axis the endocrine system regulates the phosphate balance by influencing the kidney, gut, and bone. Other hormones, including thyroid, insulin, glucagon, glucocorticosteroid, and thyrocalcitonin, play a lesser role in regulation of phosphate metabolism. Because of the complex control of phosphate homeostasis, various clinical conditions may lead to hypophosphatemia. These include nutritional repletion, gastrointestinal malabsorption, use of phosphate binders, starvation, diabetes mellitus, and increased urinary losses due to tubular dysfunction. The clinical picture of phosphate depletion is manifested in different organs and is due mainly to the fall in intracellular levels of ATP and decreased availability of oxygen to the tissues, secondary to 2,3-DPG depletion. The various manifestations of phosphate depletion are listed in Table 2. The treatment of hypophosphatemia consists of administering enteral or parenteral phosphate salts. An important aspect of dealing with the potentially serious effects of phosphate depletion is to prevent the depletion from happening in the first place. Hyperphosphatemia can occur in renal failure, hemolysis, tumor lysis syndrome, and rhabdomyolysis. The treatment of hyperphosphatemia usually consists of fluid administration (in the absence of kidney failure). In chronic hyperphosphatemia, phosphate binders such as aluminum and magnesium salts can reduce the phosphate load. The use of these phosphate binders is limited by their potential side effects.


Cinematherapy and film as an educational tool in undergraduate psychiatry teaching: a case report and review of the literature.
Film possesses an extraordinary power and offers an unrivalled medium for entertainment and escapism. There are many films that revolve around a mental illness theme and the medical specialty that most commonly features in motion picture is psychiatry. Over the last few decades films have become increasingly used as an educational tool in the teaching of psychiatry topics such as mental state examination to undergraduate students. Above and beyond its utility in pedagogy, film also has the power to heal and the term cinematherapy has been coined to reflect this. Indeed, there are case studies of people with first-hand experience of psychopathology who report that watching films with a mental illness theme has contributed to their recovery. We provide a first person narrative from an individual with schizophrenia in which he expounds on the concepts of cinematherpy and metaphorical imagery in films which theme on psychosis.


Effect of modulation of epithelial-mesenchymal transition regulators Snail1 and Snail2 on cancer cell radiosensitivity by targeting of the cell cycle, cell apoptosis and cell migration/invasion.
Cancer is one of the leading causes of cancer-associated mortality worldwide. Several strategies of treatment, including radiotherapy, have been developed and used to treat this disease. However, post-treatment metastasis and resistance to treatment are two major causes for the limited effectiveness of radiotherapy in cancer patients. Epithelial-mesenchymal transition (EMT) is regulated by SNAIL family transcription factors, including Snail1 and Snail2 (Slug), and serves important roles in progression and cancer resistance to treatment. Snail1 and Slug also have been shown to be implicated in cancer treatment resistance. For resolving the resistance to treatment problems, combining the modulation of gene expression with radiotherapy is a novel strategy to treat patients with cancer. The present review focuses on the effect of Snail1 and Slug on cancer radiosensitivity by targeting cell apoptosis, the cell cycle and cell migration/invasion.


A prospective study of the role of sleep related disordered breathing as a risk factor for motor vehicle crashes and the development of systemic complications in non-commercial drivers.
Sleep related disordered breathing (SRDB), is an established risk factor for motor vehicle crashes (MVCs) involving commercial drivers. The role of SRDB in motor vehicle crashes involving non-commercial drivers is not well established. Drivers involved in MVCs who were admitted to an American College of Surgeons accredited Level I trauma center for treatment of their injuries, and who could give informed consent and provide verbal responses to screening questionnaires were eligible for enrolment in this study. Two questionnaires previously validated for screening patients at risk for sleep disturbances (The Epworth Sleepiness Scale (ESS) and The Berlin Questionnaire (BQ)) were administered. Questionnaire results associated with an 85% sensitivity for predicting obstructive sleep apnea were considered positive. In this study we tested the hypothesis that patients at risk for SRDB, as measured by validated questionnaires, are at an increased risk being involved in MVCs. Between March and October 2010, 71 consecutive patients were offered enrolment in this study with 56 agreeing to participate in this study. Six were previously diagnosed with SRDB with only one being compliant and effectively treated at the time of their MVC. Forty-two patients (75%) had responses to the questionnaires that indicated that the patients were at high risk for SRDB. Six patients suffered systemic complications, including pleural effusions, pneumonia and arrhythmias, during their hospitalization with five (83%) having abnormal questionnaire responses indicating that the patient was at high risk for SRDB. The high incidence of positive responses to the sleep questionnaires is consistent with the hypothesis that SRDB is potentially a significant risk factor for MVCs. Furthermore the observation that systemic complications were seen more commonly in those with SRDB, while not unexpected, is a novel observation. Further studies are needed to validate these findings in a larger cohort of patients as well as determining if these patients are truly at a greater risk for systemic complications. If replicated these observations would suggest that effective therapy for disordered sleep could play a significant role in an injury prevention process.


Access to yellow fever travel vaccination centres in England, Wales, and Northern Ireland: A geographical study.
More than 700,000 trips were made by residents in England, Wales, and Northern Ireland (EWNI) in 2015 to tropical countries endemic for yellow fever, a potentially deadly, yet vaccine-preventable disease transmitted by mosquitoes. The aim of this study was to map the geographical accessibility of yellow fever vaccination centres (YFVC) in EWNI. The location of 3208 YFVC were geocoded and the average geodetic distance to nearest YFVC was calculated for each population unit. Data on trips abroad and centres were obtained regionally for EWNI and nationally for the World Top20 countries in terms of travel. The mean distance to nearest YFVC was 2.4 km and only 1% of the population had to travel more than 16.1 km to their nearest centre. The number of vaccines administered regionally in EWNI was found correlated with the number of trips to yellow fever countries. The number of centres per 100,000 trips was 6.1 in EWNI, which was below United States (12.1) and above the rest of Top20 countries. The service availability was in line with demand regionally. With the exception of remote, rural areas, yellow fever vaccination services were widely available with only short distances to cover for the travelling public.


Parasitic meningoencephalitis in nurse sharks (Ginglymostoma cirratum).
Based on microscopic examination of the brains of seven wild-caught nurse sharks (Ginglymostoma cirratum), we observed a severe meningoencephalitis associated with numerous parasitic granulomas. The parasites were larval nematodes with morphological characteristics of the Superfamily Dracunculoidea. Although meningeal larval aggregates were associated with chronic inflammation, additional parasitic nodules found on the endocardial surface and perimandibular region did not provoke an inflammatory response. Neither the route of infection nor life cycle were determined.


Granulomatosis with Polyangiitis (Wegener Granulomatosis) with Unusual Presentation.
We came across a 32 years old male admitted in our hospital with prolonged low-grade fever, haemoptysis, leg swelling, weight loss, purpuric rashes and malaena. He received anti-TB treatment at another hospital without any improvement. He was pale with bullous and purpuric lesions over legs and feet. He also had features of consolidation over both lung fields. His CRP was 312mg/L, Urine R/M/E showed 40-50 RBC/HPF, Chest X-ray showed features of bilateral consolidation, c-ANCA-10U/L (positive); Tracheal aspirate for AFB was found to be negative. We diagnosed the case as Granulomatosis with Polyangitis (WG) and started treatment with steroid and cyclophosphamide. But the patient could not be saved probably due to delay in starting management.


Sequential control of hepatitis B virus in a mouse model of acute, self-resolving hepatitis B.
The determinants of an immune response to the human hepatitis B virus (HBV) are poorly understood. As studies in man and chimpanzees are limited, we aimed at developing a model of self-limiting hepatitis B in mice that helps to dissect the control of HBV by humoral and cellular immune responses. Adenoviral vectors containing 1.3-fold HBV genomes allowed an efficient and reproducible transfer of HBV genomes into mouse livers and initiated HBV replication in mice. HBV transcripts were detected in mouse livers for more than 3 months. HBsAg and HBeAg peaked around day 6 and slowly declined thereafter. A two-phase mild to moderate liver inflammation with elevated serum alanine transaminase activities was observed around day 7 and around day 70 when the vast majority of HBV-specific T cells were detected in the liver. HBV was initially controlled when specific and nonspecific T cells infiltrated the liver and intrahepatic interferon γ levels peaked around day 7, but replicated again from day 10 to day 24 and persisted at low levels thereafter despite the presence of HBV-specific T cells. Finally, HBV replication was terminated after a sufficient B-cell response had been mounted- indicated by anti-HBs seroconversion around day 35. HBV-specific T cells infiltrated the liver a second time around day 70 postinfection. This demonstrates that the established mouse model allows studying the onset and termination of HBV infection and will help to dissect the determinants of HBV control and clearance by the immune response.


Perception of the threat of War in Israel- implications for future preparedness planning.
It has been recently reported that the preparedness of the Israeli public to a war scenario is mediocre. These findings suggest a need to study the psychosocial mechanisms behind individual motivation to engage in preparedness behavior. One component of these mechanisms is the perception of threat. The purpose of this study is to portray the perception of the threat of war by the Israeli public and to deduce possible implications for resilience-promoting policies. Portions of the data accumulated in a telephone-based random sampling of 503 households (representing the Israeli population) performed in October 2013 were utilized to examine the perception of the threat of war by Israelis. The questionnaire was used to examine the level of household preparedness, as well as attitudes toward perception of threat, preparedness responsibility, willingness to search for information, and sense of preparedness. Statistical analysis was performed to determine the correlations between different components of threat perception, and to evaluate the preparedness promoting features of specific perception factors. The data suggest that the perception of threat is influenced by different socio-demographic factors. In particular, age, religion and education seem to play an important role in the perception of threat. Compared to data collected almost a decade ago, the likelihood perception and threat intrusiveness rates were significantly reduced. The regression analysis suggests that perception of the severity of the impact on a family's routine and willingness to search for information, two known preparedness promoting factors, can be predicted by various socio-demographic and threat perception components. The data suggest that the Israeli public, post the Second Lebanon War (2006) and the Gaza conflicts of 2009 and 2012, perceives the probabilities of war and being affected by it as diminished. The Israeli public demonstrates what can be considered as the unique characteristics of a war-victimized population. Implications for a future resilience-promoting policy were discussed.


Triplet state quenching of phenosafranine dye by indolic compounds studied by transient absorption spectroscopy.
The interaction of the triplet state of the synthetic dye phenosafranine (3,7-diamino-5-phenylphenazinium chloride) with indolic compounds of biological relevance was investigated in water by means of laser flash photolysis. The rate constants for the triplet quenching were determined. The quenching process may be explained by an electron transfer from the indole to the dye in its triplet state. The rate constants present a typical dependence of an electron transfer process with the one-electron oxidation potential of the indole. Indole-3-acetic acid and its homologous indole propionic and indole butyric acids are the most effective quenchers with rate constants reaching the diffusion limit. Rate constants for indole itself, tryptophan and indole-3 carboxylic acid are one order of magnitude lower. The electron transfer nature of the quenching reaction is further confirmed by the detection of the semi-reduced form of the dye by its transient absorption. The absorption coefficients of the transient species were estimated, and the quantum yield of the charge separation process was determined. The efficiency of formation of radical species is between 60 and 90% of the triplets intercepted.


Interaction between human lung fibroblasts and T-lymphocytes prevents activation of CD4+ cells.
T lymphocytes are demonstrated to play an important role in several chronic pulmonary inflammatory diseases. In this study we provide evidence that human lung fibroblasts are capable of mutually interacting with T-lymphocytes leading to functionally significant responses by T-cells and fibroblasts. Human lung fibroblast were co-cultured with PMA-ionomycin activated T-CD4 lymphocytes for 36 hours. Surface as well as intracellular proteins expression, relevant to fibroblasts and lymphocytes activation, were evaluated by means of flow cytometry and RT-PCR. Proliferative responses of T lymphocytes to concanavalin A were evaluated by the MTT assay. In lung fibroblasts, activated lymphocytes promote an increase of expression of cyclooxygenase-2 and ICAM-1, expressed as mean fluorescence intensity (MFI), from 5.4 +/- 0.9 and 0.7 +/- 0.15 to 9.1 +/- 1.5 and 38.6 +/- 7.8, respectively. Fibroblasts, in turn, induce a significant reduction of transcription and protein expression of CD69, LFA-1 and CD28 in activated lymphocytes and CD3 in resting lymphocytes. In activated T lymphocytes, LFA-1, CD28 and CD69 expression was 16.6 +/- 0.7, 18.9 +/- 1.9 and 6.6 +/- 1.3, respectively, and was significantly reduced by fibroblasts to 9.4 +/- 0.7, 9.4 +/- 1.4 and 3.5 +/- 1.0. CD3 expression in resting lymphocytes was 11.9 +/- 1.4 and was significantly reduced by fibroblasts to 6.4 +/- 1.1. Intracellular cytokines, TNF-alpha and IL-10, were evaluated in T lymphocytes. Co-incubation with fibroblasts reduced the number of TNF-alpha positive lymphocytes from 54.4% +/- 6.12 to 30.8 +/- 2.8, while IL-10 positive cells were unaffected. Finally, co-culture with fibroblasts significantly reduced Con A proliferative response of T lymphocytes, measured as MTT absorbance, from 0.24 +/- 0.02 nm to 0.16 +/- 0.02 nm. Interestingly, while the activation of fibroblasts is mediated by a soluble factor, a cognate interaction ICAM-1 mediated was demonstrated to be responsible for the modulation of LFA-1, CD28 and CD69. Findings from this study suggest that fibroblasts play a role in the local regulation of the immune response, being able to modulate effector functions of cells recruited into sites of inflammation.


Temporal trend and cross-sectional characterization of urinary concentrations of glyphosate in Japanese children from 2006 to 2015.
Over the past two decades, domestic shipments of glyphosate (Gly), in the form of an ionic salt, have been increasing steadily in Japan. This increase has raising concerns about the effects of chemical exposure on children. The International Agency for Research on Cancer classified Gly as a "probably carcinogenic to humans (Group 2A)" in 2015. The purpose of the current study was to analyze Gly in urine samples of Japanese children to determine temporal changes, seasonal changes, and gender differences. First-morning urine samples were obtained from 50 Japanese children (4-6-year-old) in October of 2006, 2011, and 2015 (total = 150) to investigate the temporal trends in urinary Gly concentrations. Additionally, first-morning urine samples were collected from 3-year-old children in August-September of 2012 (summer; n = 42) and in February of 2013 (winter; n = 42) to investigate the seasonal and gender differences, and the correlations between urinary Gly concentrations and insecticide exposure biomarkers. Urine samples were analyzed to measure for Gly using a liquid chromatography with tandem mass spectrometry (LC-MS/MS). Detectable Gly concentrations were found in 41% of the 234 children. The 75th percentile and maximum concentrations of urinary Gly were 0.20 and 1.33 μg/L, respectively. The urinary Gly concentration in 2015 was significantly higher than in 2006, suggesting that the Gly exposure levels have been increasing. No seasonal or gender-specific differences in urinary Gly concentrations were observed, and no correlation with insecticide exposure biomarkers was found. This study revealed that Gly exposure trends show an increase between 2006 and 2015, and that season and gender were not the exposure-determining factors. Overall, urinary concentrations of Gly were comparable with studies from other countries.


Hepatic AL Amyloidosis without Significant Light Chain Elevation in a Patient Treated with CyBorD Plus Daratumumab.
BACKGROUND Immunoglobulin light chain (AL) amyloidosis is a plasma cell disorder in which excess light chain deposits in tissues, resulting in organ dysfunction and damage. Typically, AL amyloidosis presents as a systemic disease affecting multiple organs, and most patients have elevated serum free light chains. However, the presentation of AL amyloidosis is highly variable. The purpose of this case report is to raise awareness of the atypical presentations of AL amyloidosis in order to facilitate more rapid diagnosis, which has the potential to prevent additional organ damage when appropriate therapy is provided. CASE REPORT We describe a case of AL amyloidosis with amyloid deposition confined to the liver and bone marrow and lack of significant serum light chain elevation. The patient initially presented with a spontaneous hepatic hematoma, and was ultimately found to have hepatic AL amyloidosis, with monoclonal plasma cells in the bone marrow and monoclonal protein on serum protein electrophoresis. Our patient responded to treatment with cyclophosphamide-bortezomib-dexamethasone, the anti-CD38 antibody daratumumab, and autologous stem cell transplant, resulting in hematological and organ response. CONCLUSIONS AL amyloidosis can present with end-organ damage confined to isolated organs, and it can present without the expected elevation in serum light chains. Such patients can benefit from appropriate treatment, including traditional chemotherapy, daratumumab, and stem cell transplant. As effective treatments for AL amyloidosis are now available, prompt diagnosis has the potential to limit end-organ damage and potentially improve patient outcomes.


Isolation of lectins by affinity chromatography with porcine plasma proteins immobilized on agarose.
To develop a convenient method to isolate lectins, we prepared an affinity gel by coupling plasma proteins with agarose beads under conditions where the pH did not exceed 7.5. The validity of the use of this affinity gel in combination with elution using a hapten saccharide was confirmed by isolation of concanavalin A from Jack bean meal. Successful application of the method was demonstrated by isolation of two novel vegetable lectins from udo (Aralia cordate) and wasabi (Wasabia japonica). The method would be useful to isolate new lectins from various sources including plant and animal tissues.


Zeta potential determination as a new way of stationary phases characterization for liquid chromatography.
A set of seven homemade octadecyl silica-based bonded phases was investigated. Their zeta potential data in methanol and ACN as well as in methanol-water and ACN-water solution were obtained using Zetasizer. The influence of both the coverage density of bonded ligands and the end-capping of the modified surface on these data was investigated. Presented results may give useful information about the accessibility of the residual silanols in different mobile phases during the chromatographic analysis. Those measurements may be useful to choose chemically bonded stationary phases for CEC. The results also confirm the phenomena of anion exclusion from the pores of stationary-bonded phase.


[Education for chronic cardiologic diseases in a transversal multidisciplinary unit: the experience of a general hospital center].
Treatments for congestive heart failure, hypertension and cardiovascular risk have significantly changed and have become more complex. The have also become more and more effective thanks to the results of great clinical studies that have enabled European and North-American societies to issues recommendations. The observance of the pharmacological and non-pharmacological treatments requires the education of patients and their family following guidelines that have been clearly defined by the European Society of Cardiology. This education, in which the technic of communication is very important, is common to a lot of chronic diseases and requires adequate material and human resources in order to have an optimal quality of treatment. In a society in which spending is on rise, getting such resources is not easy. However, putting in common resources of several departments can be a good solution. The experience of the Hospital Center of Douai (France) lead to the creation of a Transversal Education Unit at the end of the year 2003. This unit centralizes the efforts of several departments of care like pneumology, pediatrics, diabetology, nutrition and cardiology and allows patients suffering from co-morbidities to have access to various programs of this unit.


In-patient costs of agitation and containment in a mental health catchment area.
There is a scarce number of studies on the cost of agitation and containment interventions and their results are still inconclusive. We aimed to calculate the economic consequences of agitation events in an in-patient psychiatric facility providing care for an urban catchment area. A mixed approach combining secondary analysis of clinical databases, surveys and expert knowledge was used to model the 2013 direct costs of agitation and containment events for adult inpatients with mental disorders in an area of 640,572 adult inhabitants in South Barcelona (Spain). To calculate costs, a seven-step methodology with novel definition of agitation was used along with a staff survey, a database of containment events, and data on aggressive incidents. A micro-costing analysis of specific containment interventions was used to estimate both prevalence and direct costs from the healthcare provider perspective, by means of a mixed approach with a probabilistic model evaluated on real data. Due to the complex interaction of the multivariate covariances, a sensitivity analysis was conducted to have empirical bounds of variability. During 2013, 918 patients were admitted to the Acute Inpatient Unit. Of these, 52.8% were men, with a mean age of 44.6 years (SD = 15.5), 74.4% were compulsory admissions, 40.1% were diagnosed with schizophrenia or non-affective psychosis, with a mean length of stay of 24.6 days (SD = 16.9). The annual estimate of total agitation events was 508. The cost of containment interventions ranges from 282€ at the lowest level of agitation to 822€ when verbal containment plus seclusion and restraint have to be used. The annual total cost of agitation was 280,535€, representing 6.87% of the total costs of acute hospitalisation in the local area. Agitation events are frequent and costly. Strategies to reduce their number and severity should be implemented to reduce costs to the Health System and alleviate patient suffering.


Prevalence of computer vision syndrome: A systematic review and meta-analysis.
This review aimed to estimate the prevalence of computer vision syndrome (CVS) in the general population and subgroups. A search was conducted in the following the databases: PubMed, SCOPUS, EMBASE, and Web of Science until February 13, 2023. We included studies that assessed the prevalence of CVS in any population. The Joanna Briggs Institute's critical appraisal tool was used to evaluate the methodological quality. A meta-analysis of the prevalence of CVS was done using a random-effects model, assessing the sources of heterogeneity using subgroup and meta-regression analyses. A total of 103 cross-sectional studies with 66 577 participants were included. The prevalence of CVS was 69.0% (95% CI: 62.3 to 75.3; I2: 99.7%), ranging from 12.1 to 97.3% across studies. Point prevalence was higher in women than in men (71.4 vs. 61.8%), university students (76.1%), Africa (71.2%), Asia (69.9%), contact lens wearers (73.1% vs. 63.8%) in studies conducted before the COVID-19 pandemic (72.8%), and in those that did not use the CVS-Q questionnaire (75.4%). In meta-regression, using the CVS-Q scale was associated with a lower prevalence of CVS. Seven out of ten people suffer from CVS. Preventive strategies and interventions are needed to decrease the prevalence of this condition which can affect productivity and quality of life. Future studies should standardize a definition of CVS.


An evaluation of a method for the detection of sensory ganglia in product derived from advanced meat recovery systems.
A method is described for the identification of dorsal root ganglia (DRG)-associated sensory neurons within advanced meat recovery (AMR) product derived from bovine vertebral columns. This method relies on the unique microanatomy of sensory neurons and immunohistochemical staining, primarily for glial fibrillary acidic protein. Sensory neurons are variably sized unipolar neurons, exhibiting a single-cell process that is rarely seen in histologic sections. These neurons are surrounded by a prominent ring of glial fibrillary acidic protein-positive satellite cells that produce a distinctive and readily identifiable staining pattern in histologic sections. Fragmented DRG were detected to the 0.25% level in samples of ground beef or nonvertebral-origin AMR product spiked with these sensory ganglia. Similarly examined commercially produced nonvertebral-origin AMR product (n = 157) did not contain sensory ganglia, while 3.3% of vertebral-origin AMR product (n = 364) contained fragmented DRG.