No evidence of an association between size and levels of four per- and polyfluorinated substances (PFAS) in perch (Perca fluviatilis).

It was assessed how the size of perch (Perca fluviatilis) is related to levels of four per- and polyfluorinated substances (PFAS) in its muscle tissue. These were PFOS, PFNA, PFOA, and PFHxS, for which the sum, denoted as ΣPFAS4, has a tolerable intake derived by the European Food Safety Authority. The results indicate that, in contrast to, e.g., mercury levels, ΣPFAS4 levels in perch muscle do not increase with increasing weight of the fish, which implies that consuming larger perch does not increase the risk of exceeding the TWI of ΣPFAS4, in relation to consuming smaller perch. Therefore, for risk assessment, analyzing samples of smaller perch is sufficient, demanding less effort to catch. The credibility of the results was strengthened by applying the same statistical model to mercury levels in the same samples. As expected, larger fish had generally higher levels than small fish for mercury.

Fluctuations in loneliness due to changes in frequency of social interactions among older adults: a weekly based diary study.

OBJECTIVES: Loneliness functionally varies and is determined by the degree of interaction with others. We examined weekly fluctuations in reported loneliness as a function of frequency of social interactions in old age. We hypothesized that emotional and social components of loneliness would be related to different types of social relationships. DESIGN: Participants reported their feeling of loneliness and their social interaction quantity (frequency of meetings) via a weekly based diary, over 6 weeks. SETTING: Diary study. PARTICIPANTS: The study included 55 older adults with different dwelling arrangements (M = 73.4, SD = 6.97). MEASUREMENTS: Measures of Loneliness (the De Jong-Gierveld Loneliness Scale), Social Interaction and Contact, and sociodemographic parameters were used. RESULTS: Social and emotional loneliness fluctuated over the course of the 6-week study. Frequency of meeting friends was related to emotional loneliness and total feelings of loneliness. Frequency of meeting close/trusted figures was related to emotional loneliness which appeared the following week. Other variables were not associated with either changes in loneliness or its dimensions. CONCLUSIONS: Loneliness in old age is changeable. The emotional component of loneliness seems to be dominant in determining overall feelings of loneliness and is more sensitive to externally chosen social interaction.

The need to consider the service life of all components of a modern MSW landfill liner system.

The long-term performance of a geosynthetic clay liner (GCL) above a drainage layer and a geocomposite drain (GCD) are investigated. Full-scale tests are used to: (i) assess the integrity of GCL and GCD in a double composite liner below a defect in the primary geomembrane with ageing, and (ii) establish the head at which there was internal erosion in GCL without a carrier geotextile (GTX) such that the bentonite is in direct contact with the underlying gravel drainage. Six years after contact with simulated landfill leachate at 85 °C through an intentional defect on the geomembrane, the GCL resting on the GCD had failed due to degradation of the GTX between the bentonite and the core of the GCD and subsequent erosion of the bentonite into the core structure of the GCD was observed. In addition to complete degradation of its GTX at some locations, the GCD had also experienced extensive stress cracking and rib rollover. The second test demonstrates that if a suitable gravel drainage layer had been used instead of the GCD, the GTX component of the GCL would not have been required for acceptable long-term performance under normal design conditions and indeed could withstand a head of up to 15 m before problems became evident. The findings serve as a warning landfill designers and regulators that more attention must be paid to the service life of all components of double liner systems used in Municipal Solid Waste (MSW) landfills.

Characterization and evaluation of the therapeutic benefits of pure and lanthanides mono- and co-doped zinc oxide nanoparticles.

The effect of Lanthanides-doping on the structural, optical, morphological, antibacterial and anticancer properties of zinc oxide (ZnO) nanoparticles was investigated. Pure ZnO, Zn0.9La0.1O, Zn0.9Ce0.1O, and Zn0.9La0.05Ce0.05O were fabricated through the chemical co-precipitation route. The structural and morphological properties were studied using the X-ray diffraction (XRD) and transmission electron microscopy (TEM), respectively. The optical properties were analyzed by photoluminescence spectroscopy (PL). The inhibitory effect of the synthesized nanoparticles (NPs) was assessed against six bacterial strains using the agar well diffusion and broth micro-dilution methods. The anticancer potential of the synthesized NPs was assessed against two human colon cancer cell lines Caco-2 and HCT-116. The appearance of the La2O3 and CeO2 secondary phases upon doping La3+ and Ce3+ ions induced structural and morphological changes. The large distorted hexagonal morphology of pure ZnO is transformed into small sized distorted hexagonal form. The photoluminescence spectra revealed the point defects resulting from Lanthanum (La) and cerium (Ce) doping. The prepared NPs significantly inhibited the growth of the six investigated bacteria and induced cytotoxic effects and morphological changes against Caco-2 and HCT-116 cell lines. This study showed that doping ZnO with lanthanide ions such as La3+ and Ce3+ provide promising biological applications. These NPs showed a potent antibacterial and anticancer effect towards the investigated bacterial strains and colon cancer cell lines. These findings point to the importance of the biological applications of NPs, and the possibility of investigating other biomedical applications for NPs.

Evaluation of single domain antibodies as nuclear tracers for imaging of the immune checkpoint receptor human lymphocyte activation gene-3 in cancer.

Recent advancements in the field of immune-oncology have led to a significant increase in life expectancy of patients with diverse forms of cancer, such as hematologic malignancies, melanoma and lung cancer. Unfortunately, these encouraging results are not observed in the majority of patients, who remain unresponsive and/or encounter adverse events. Currently, researchers are collecting more insight into the cellular and molecular mechanisms that underlie these variable responses. As an example, the human lymphocyte activation gene-3 (huLAG-3), an inhibitory immune checkpoint receptor, is increasingly studied as a therapeutic target in immune-oncology. Noninvasive molecular imaging of the immune checkpoint programmed death protein-1 (PD-1) or its ligand PD-L1 has shown its value as a strategy to guide and monitor PD-1/PD-L1-targeted immune checkpoint therapy. Yet, radiotracers that allow dynamic, whole body imaging of huLAG-3 expression are not yet described. We here developed single-domain antibodies (sdAbs) that bind huLAG-3 and showed that these sdAbs can image huLAG-3 in tumors, therefore representing promising tools for further development into clinically applicable radiotracers.

The diagnosis, clinical findings and treatment options for Parkinson's disease patients attending a tertiary referral voice clinic.

BACKGROUND: Parkinson's disease is a degenerative disorder of the central nervous system, mainly affecting motor functions including the voice. The aetiology of dysphonia changes throughout the course of disease progression. OBJECTIVES: This study aimed to determine the laryngeal changes seen in early-, mid- and late-stage Parkinson's disease. Thirteen patients with Parkinson's disease are presented, representing the largest series of voice patients with Parkinson's disease seen in a voice clinic in the literature. METHOD: Age, gender, severity of handicap caused by voice disorder and possible associated reflux symptoms were examined. RESULTS: Laryngeal function appeared to change gradually with progression of the disease, and may have been affected by the presence of pre-existing laryngeal pathology. CONCLUSION: Laryngeal function in Parkinson's disease appears to go through a series of changes that may be helped by both therapeutic and surgical interventions. These patients should be treated within the confines of a voice clinic multidisciplinary model.

Two new proanthocyanidin trimers isolated from Cistus incanus L. demonstrate potent anti-inflammatory activity and selectivity to cyclooxygenase isoenzymes inhibition.

Two new proanthocyanidin trimers have been isolated from Cistus incanus herb; gallocatechin-(4α→6)-gallocatechin-(4α→8)-gallocatechin (compound 1) and epigallocatechin-3-O-gallate-(4ß→8)-epigallocatechin-3-O-gallate-(4ß→8)-gallocatechin (compound 2). The structures were determined on the basis of 1D- and 2D-NMR (HSQC, HMBC) of their peracetylated derivatives, MALDI-TOF-MS and by acid-catalysed degradation with phloroglucinol. A more abundant proanthocyanidin oligomer was also isolated, purified and its chemical constitution studied by (13)C-NMR and phloroglucinol degradation. The mean molecular weight of the polymer was estimated to be about 7 to 8 flavan-3-ol-units with a ratio of procyanidin : prodelphinidin units at 1:5, some of which are derivatised by gallic acid. Water extract and higher oligomeric proanthocyanidin fractions of C. incanus significantly inhibited TPA-induced oedema when applied topically at doses of 0.5 and 1 mg/ear in mice. Furthermore, the extracts and the pure compounds inhibited COX-1 and COX-2 activities. In addition, compound 2 exhibited an IC50 of 4.5 µM against COX-2 indicating its high selectivity towards COX-2.

Some quality attributes of low fat ice cream substituted with hulless barley flour and barley ß-glucan.

The purpose of this paper is to investigate some quality attributes of low fat ice cream (LFIC) substituted with hulless barley flour (HBF) and barley ß-glucan (BBG). The methodology included in this paper is based on adding HBF (1, 2, 3 and 4 %) as a partial substitution of skim milk powder (SMP) and BBG (0.40 %) as a complete substitution of carboxy methyl cellulose (CMC). All mixes and resultant ice cream samples were evaluated for their physicochemical properties as well as the sensory quality attributes.The results indicated that substitution of SMP with HBF significantly increased total solids (TS), fat and crude fiber, while crude protein and ash significantly decreased in ice cream mixes. BBG exhibited the same manner of control. Specific gravity was gradually increased with adding HBFand BBG in the mixes and therefore the overrun percent was significantly changed in the resultant ice cream. Adding HBF in ice cream formula led to significant decrease in acidity with higher freezing point and the product showed higher ability to meltdown. BBG treatment showed the same trend of control. Values of flow time and viscosity significantly increased with increasing HBF in the ice cream mixes, but these values significantly decreased in BBG mix. The time required to freeze ice cream mixes was decreased with increasing the ratio of HBF but, increased in BBG treatment. The substitution of SMP with 1 and 2 % HBF significantly (P ≤ 0.05) enhanced sensory attributes of ice cream samples. While, BBG treatment achieved mild score and acceptability.

Test de Parche como método diagnóstico de las reacciones adversas a medicamentos / Patch test as a diagnostic method for adverse drug reactions

Las reacciones adversas a medicamentos (RAM) son un motivo frecuente de consulta en la práctica dermatológica. La hipersensibilidad a fármacos es una causa común de RAM, y es de gran relevancia confirmar este mecanismo para que el paciente evite futuras exposiciones. El test de parche tiene un rol relevante en el proceso diagnóstico de las reacciones de hipersensibilidad no inmediatas, otros test como la intradermorreacción o el test de provocación son más invasivos o de alto riesgo, y los exámenes in vitro para reacciones tardías no se encuentran fácilmente disponibles. El problema es que existe escasa estandarización del procedimiento y el valor predictivo del examen es incierto. En esta revisión exponemos la mejor evidencia disponible, lo que permitirá al especialista decidir cuándo hacer este examen y cómo interpretar sus resultados.

Adverse drugs reactions (ADR) are a frequent diagnosis in dermatological practice. Drug hypersensitivity is a common ADR etiology, and it is greatly relevant to confirm this mechanism to avoid future exposures of the patient to the culprit drug. Patch test has an outstanding role in non-immediate hypersensitivity reactions diagnosis process, other tests like intradermal reaction or provocation test are more aggressive or implies more risk, and in-vitro test for non-inmediate reactions are not easily available. One of the main problems of patch test is the lack of standarization of the procedure and the uncertain predictive value. In this review is exposed the best evidence available, so the specialist could decide when to do the test and how interpret its results.

Tuberculosis incidence trends in Saudi Arabia over 20 years: 1991-2010.

OBJECTIVE: To evaluate tuberculosis (TB) incidence rates and trends over a period of 20 years (1991-2010) and assess the impact of the National TB Control Program (NTP) on incidence trends. METHODS: This is a retrospective study of TB surveillance data reported by the Ministry of Health. We evaluated TB incidence data by nationality, age, and region of the country and assessed incidence trends over 20 years of study. Chi-squared test was used to assess trend change and its significance. RESULTS: There were a total of 64,345 reported TB cases over the study period. Of these 48% were Non-Saudis. TB annual incidence rate ranged between 14 and 17/100,000. For Saudis, the rate ranged between 8.6 and 12.2/100,000. Non-Saudis had 2-3 times higher incidence. Disease trend was rising over the first 10 years of the study period then it started to fall slightly. The incidence increased with age, but only people older than 45 years showed a declining trend. Regional variations were observed. Makkah and Jazan regions had the highest incidence rates. Disease trends were rising over the last 10 years in Makkah and Central regions. CONCLUSION: TB control seems to be facing some challenges in several regions of the Kingdom. NTP needs to evaluate and improve TB control strategies in order to reduce disease incidence to elimination levels.

Rectal hyposensitivity for non-noxious stimuli, postprandial hypersensitivity and its correlation with symptoms in complete spinal cord injury with neurogenic bowel dysfunction.

STUDY DESIGN: Prospective clinical study. OBJECTIVES: To assess fasting and postprandial (PP) perception of rectal distension and its correlation with symptoms in patients with spinal cord injury (SCI) and neurogenic bowel dysfunction compared to ten healthy subjects (HS). SETTING: Experimental Medicine and Motility Unit, Mexico General Hospital and National Institute of Rehabilitation. METHODS: Twenty patients with complete SCI at cervical, thoracic and lumbar levels [American Spinal Injury Association (ASIA) A] were studied. Rectal sensitivity was evaluated with a barostat. RESULTS: In SCI patients, while lower the rectal tone more time was used for defecate (R=0.50, P=0.048) and more PP episodes of fecal incontinence occur (R=0.54, P=0.030). The thresholds for non-noxious stimuli of first (23.6 mmHg, CI 19.5-27.7) vs 14.0 (CI 10.9-17.1), P=0.004; gas (27.9 mmHg, CI 19.9-35.8) vs 17.9 mmHg (CI 14.25-21.69), P=0.02 and urge-to-defecate sensation (33.2 mmHg, CI 27.5-38.8) vs 22.4 mmHg (CI 17.9-26.9), P=0.01 were reported by SCI patients at higher pressure than HS, respectively. SCI patients reported PP pain sensation at a lower pressure than controls (27.8 mmHg, CI 21.5-34.2 vs 36.5 mmHg, CI 31.8-41.2), P=0.04. CONCLUSION: SCI patients preserve rectal sensation, present rectal hyposensitivity for non-noxious stimuli and PP hypersensitivity. Lower rectal tone was related to the time used for defecate and with fecal incontinence. The results suggest that an intact neural transmission between the spinal cord and higher centres is indispensable for noxious stimulus, but not for non-noxious stimuli. Also, barostat sensitivity studies can complement ASIA criteria to verify a complete injury.

Medical and surgical management of esophageal and gastric motor dysfunction.

he occurrence of esophageal and gastric motor dysfunctions happens, when the software of the esophagus and the stomach is injured. This is really a program previously established in the enteric nervous system as a constituent of the newly called neurogastroenterology. The enteric nervous system is composed of small aggregations of nerve cells, enteric ganglia, the neural connections between these ganglia, and nerve fibers that supply effectors tissues, including the muscle of the gut wall. The wide range of enteric neuropathies that includes esophageal achalasia and gastroparesis highlights the importance of the enteric nervous system. A classification of functional gastrointestinal disorders based on symptoms has received attention. However, a classification based solely in symptoms and consensus may lack an integral approach of disease. As an alternative to the Rome classification, an international working team in Bangkok presented a classification of motility disorders as a physiology-based diagnosis. Besides, the Chicago Classification of esophageal motility was developed to facilitate the interpretation of clinical high-resolution esophageal pressure topography studies. This review covers exclusively the medical and surgical management of the esophageal and gastric motor dysfunction using evidence from well-designed studies. Motor control of the esophagus and the stomach, motor esophageal and gastric alterations, treatment failure, side effects of PPIs, overlap of gastrointestinal symptoms, predictors of treatment, burden of GERD medical management, data related to conservative treatment vs. antireflux surgery, and postsurgical esophagus and gastric motor dysfunction are also taken into account.

Vasculitis de vaso pequeño asociada a un producto oral usado para la caída del pelo / Small vessels vasculitis associated with a oral medication for loss hair

Se presenta el caso de una mujer de 36 años que consultó por lesiones vasculíticas en extremidades inferiores que aparecieron con relación al uso de un producto oral comercializado para la caída del pelo que contiene prosilium, vitaminas B6, B5, B8, hierro, zinc y vitamina E. Algunos elementos evolucionaron hacia la necrosis, especialmente en la pierna derecha. Los análisis de laboratorio permitieron excluir otras patologías asociadas con vasculitis, diagnosticándose una vasculitis cutánea de vaso pequeño posiblemente asociado a alguno de los componentes de dicho producto.

A 36 year old woman went for a consultation because of vasculitic lesions in her lower extremities that appeared after the use of a commercial oral product for hair loss which contains prosilium, vitamin B6, B5, B8, E, iron, and zinc. Some elements evolved towards necrosis, especially in the right leg. Laboratory analysis excluded other causes of vasculitis. The final diagnosis was a cutaneous vasculitis possible associated with some of the components of the hair loss product.

A randomized, double-blind, placebo-controlled trial of polyethylene glycol effects on fasting and postprandial rectal sensitivity and symptoms in hypersensitive constipation-predominant irritable bowel syndrome.

AIM: To assess the effect of polyethylene glycol 3350 (PEG) on fasting and postprandial (PP) perception of rectal distension and symptoms in hypersensitive constipation-predominant irritable bowel syndrome (IBS-C). METHODS: Forty-two patients meeting Rome II criteria for IBS-C and with a pain threshold of < 32 mmHg were included in a randomized, double-blind, placebo-controlled trial. Patients received either oral PEG, 3.45 g t.i.d. orally for 30 days or placebo. Rectal sensitivity was assessed before and after treatment with a barostat using the ascending method of limits, during basal and PP periods. RESULTS: No changes in fasting and PP rectal tone and thresholds for first sensation, gas sensation, urge to defecate, and pain was observed with PEG in relation to placebo. In both groups, pressure at which patients crossed the thresholds for noxious (PEG: from 28 ± 8.8 to 22 ± 6.9 mmHg) and non noxious (PEG: from 16 ± 4.9 to 12 ± 3.6 mmHg) stimuli decreased compared with pretreatment values. PEG improved consistency of faeces and showed a trend to diminish blood in faeces. PEG and placebo increased bowel movements per week (P < 0.001), and relieved symptoms without significant side-effects. CONCLUSIONS: Both PEG 3350 and placebo were clinically useful in patients with IBS-C, an effect that cannot be explained by changes in rectal tone and sensation. The results support the concept that visceral sensitivity is not stable and has a heterogeneous response to drugs, and suggest the existence of a post healing hypersensitivity state.

Sífilis en pacientes portadores de VIH o con SIDA en un servicio de enfermedades de transmisión sexual / Syphilis cases in HIV or AIDS patients in a sexually transmitted disease clinic

En relación a casos no esperados de sífilis en pacientes VIH + o con SIDA en control en un policlínico de enfermedades de transmisión sexual, se decidió revisar las fichas clínicas. Se consignaron parámetros clínicos como: número de casos, edad, sexo, preferencia sexual, etapa de la enfermedad, existencia de terapia, y parámetros de laboratorio como VDRL y recuento de linfocitos CD4. Se revisaron 1.703 historias clínicas que correspondieron a un período de 19 años. Se detectaron 171 casos de sífilis, siendo esta patología más frecuente en los pacientes de sexo masculino, de los cuales un 83 por ciento eran hombres que tenían sexo con hombres. La edad promedio fue 36,2 años y un 45 por ciento de los casos registrados fueron contagiosos debido a que clínicamente se diagnosticaron en etapas primarias y secundarias. El grupo de homosexuales presentó con mayor frecuencia sífilis y además es el grupo que fue contagiado más de una vez, en algunos casos, a pesar de estar en terapia antirretroviral.

Concerning unexpected syphilis cases in HIV or AIDS patients who were controlled in a sexually transmitted disease clinic, we decided to analyze the clinical files. We analyzed clinical variables, such as number of cases, age, gender, sexual preference, disease stage, existence of therapy and laboratory tests like VDRL and lymphocytic CD4. 1,703 files were revised over a 19 year period, detecting 171 syphilis cases, which were more frequent in men who had sex with men (83 percent). Average age was 36.2, and 45 percent of the registered cases were contagious, since they were clinically diagnosed at primary and secondary stages. Homosexuals were the group that most frequently presented syphilis, as well as having been infected more than once, in some cases, even though they were undergoing antiretroviral therapy.

Effects of traditionally used anxiolytic botanicals on enzymes of the gamma-aminobutyric acid (GABA) system.

In Canada, the use of botanical natural health products (NHPs) for anxiety disorders is on the rise, and a critical evaluation of their safety and efficacy is required. The purpose of this study was to determine whether commercially available botanicals directly affect the primary brain enzymes responsible for gamma-aminobutyric acid (GABA) metabolism. Anxiolytic plants may interact with either glutamic acid decarboxylase (GAD) or GABA transaminase (GABA-T) and ultimately influence brain GABA levels and neurotransmission. Two in vitro rat brain homogenate assays were developed to determine the inhibitory concentrations (IC50) of aqueous and ethanolic plant extracts. Approximately 70% of all extracts that were tested showed little or no inhibitory effect (IC50 values greater than 1 mg/mL) and are therefore unlikely to affect GABA metabolism as tested. The aqueous extract of Melissa officinalis (lemon balm) exhibited the greatest inhibition of GABA-T activity (IC50 = 0.35 mg/mL). Extracts from Centella asiatica (gotu kola) and Valeriana officinalis (valerian) stimulated GAD activity by over 40% at a dose of 1 mg/mL. On the other hand, both Matricaria recutita (German chamomile) and Humulus lupulus (hops) showed significant inhibition of GAD activity (0.11-0.65 mg/mL). Several of these species may therefore warrant further pharmacological investigation. The relation between enzyme activity and possible in vivo mode of action is discussed.

Dermatosis acantolíticas: a propósito de un caso / Acantholytic dermatosis: a case report

Se presenta el caso de una paciente de 64 años que ha tenido episodios recurrentes de lesiones vesiculosas en su extremidad inferior derecha, diagnosticándose una dermatosis acantolítica. Existe un espectro de enfermedades acantolíticas que histopatológicamente presentan acantolisis, pero que no comparten factores genéticos. El diagnóstico clínico puede ser extremadamente difícil y es la suma de herencia, clínica, histopatología y evolución, la que permite llegar a un diagnóstico. Se realiza una reseña de todas estas enfermedades.

We present the case of 64-year-old female patient with recurrent episodes of vesicles in her lower right limb. Histopathological study revealed acantholytic dermatosis. There is a large spectrum of acantholytic dermatosis that histopathologically presents acantholysis but does not share genetic factors. Clinical diagnosis may be extremely difficult and results in the sum of genetics, clinical findings, histopathological studies and evolution. We also present a review of these diseases.