Search

The development of the computer and what is now known as artificial intelligence (AI) has evolved over more than two centuries in a long series of steps. The date of the invention of the first computer is estimated at 1822, when Charles Babbage (1791-1871) developed his first design of a working computer on paper, based mainly on a Jacquard loom. He worked on his project together with Augusta Ada King, Countess Lovelace (née Byron) (Ada Lovelace) (1815-1852), whom he called the "Sorceress of Numbers." This work will present the profile and achievements of Charles Babbage, Augusta Ada King, Countess Lovelace, and Alan Mathison Turing (1912 - 1954), who is considered the father of computer science and artificial intelligence, and then provide an outline of the tumultuous events affecting AI up to the present., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We describe a novel assay and artificial intelligence-driven histopathologic approach identifying dermatophytes in human skin tissue sections (ie, B-DNA dermatophyte assay) and demonstrate, for the first time, the presence of dermatophytes in tissue using immunohistochemistry to detect canonical right-handed double-stranded (ds) B-DNA. Immunohistochemistry was performed using anti-ds-B-DNA monoclonal antibodies with formalin-fixed paraffin-embedded tissues to determine the presence of dermatophytes. The B-DNA assay resulted in a more accurate identification of dermatophytes, nuclear morphology, dimensions, and gene expression of dermatophytes (ie, optical density values) than periodic acid-Schiff (PAS), Grocott methenamine silver (GMS), or hematoxylin and eosin (H&E) stains. The novel assay guided by artificial intelligence allowed for efficient identification of different types of dermatophytes (eg, hyphae, microconidia, macroconidia, and arthroconidia). Using the B-DNA dermatophyte assay as a clinical tool for diagnosing dermatophytes is an alternative to PAS, GMS, and H&E as a fast and inexpensive way to accurately detect dermatophytosis and reduce the number of false negatives. Our assay resulted in superior identification, sensitivity, life cycle stages, and morphology compared to H&E, PAS, and GMS stains. This method detects a specific structural marker (ie, ds-B-DNA), which can assist with diagnosis of dermatophytes. It represents a significant advantage over methods currently in use., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study explored the integration and impact of artificial intelligence (AI) in diagnostic pathology, particularly dermatopathology, assessing its challenges and potential solutions for global health care enhancement. A comprehensive literature search in PubMed and Google Scholar, conducted on March 30, 2023, and using terms related to AI, pathology, and machine learning, yielded 44 relevant publications. These were analyzed under themes including the evolution of deep learning in pathology, AI's role in replacing pathologists, development challenges of diagnostic algorithms, clinical implementation hurdles, strategies for practical application in dermatopathology, and future prospects of AI in this field. The findings highlight AI's transformative potential in pathology, underscore the need for ongoing research, collaboration, and regulatory dialogue, and emphasize the importance of addressing the ethical and practical challenges in AI implementation for improved global health care outcomes., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Artificial intelligence (AI) can be a powerful tool for data analysis, but it can also mislead investigators, due in part to a fundamental difference between classic data analysis and data analysis using AI. A more or less limited data set is analyzed in classic data analysis, and a hypothesis is generated. That hypothesis is then tested using a separate data set, and the data are examined again. The premise is either accepted or rejected with a value p, indicating that any difference observed is due merely to chance. By contrast, a new hypothesis is generated in AI as each datum is added to the data set. We explore this discrepancy and suggest means to overcome it., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Artificial Intelligence (AI) is a very powerful new tool that is destined to markedly advance many areas of dermatology, including cosmetic dermatology, oculoplastics, cancer detection and treatment, dermatopathlogy, and identification of pathogens. Along with these are some special new risks and concerns, however, including ethical considerations, data analysis, interpretation of scientific studies, and recognizing systematic failures and fraud, particularly in generative AI. Each of these issues is reviewed collectively and in turn in this special of Clinics in Dermatology., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Recruitment of diverse and talented students to the field of neurosurgery is key to its continued growth and scientific advancement. Barriers, including poor perceptions and lack of early exposure, can impact recruitment and have been compounded by the ongoing COVID-19 pandemic. This study examines the impact of an inaugural Neurosurgery Research Consortium meeting on premedical students, assessing whether this exposure generated interest and improved perceptions of a career in neurosurgery., Methods: Premedical students were recruited to virtually attend an inaugural Neurosurgery Research Consortium developed by the affiliated medical school's American Association of Neurological Surgeons (AANS) Student Chapter. Questionnaires were distributed to students before and after the meeting to assess student demographics and perceptions of neurosurgery., Results: A total of 54 students attended the meeting, with general interest in neurosurgery, medicine, and research opportunities being the primary factors for attendance. Following the research meeting, we found that students perceived neurosurgeons to be friendlier and more approachable, with a more positive quality of life (QoL). Overall perceptions of neurosurgery improved after the meeting, but perceptions among racial and ethnic minority students did not significantly change in the areas of diversity, inclusion, and equity., Conclusions: These results suggest recruitment strategies targeting undergraduate students may improve their perception of neurosurgery as a career, and may mitigate some barriers to entry. These strategies are cost effective and easily replicable, making an easily implementable approach to provide direct insight into neurosurgery for future medical students while also promoting academic efforts in the field of neurosurgery., (Copyright © 2023 Elsevier Inc. All rights reserved.)

An infection by protozoa Eimeria spp. can cause coccidiosis, which negatively affects broiler chicken performance and causes economic and production losses. To understand the effect of coccidiosis on broilers' performance, we evaluated the independent variables and their interactions on the severity of coccidiosis in broilers that cause variation (Δ) of average daily feed intake (ADFI), average daily gain (ADG), and gain per feed (G:F) of broiler chicks using a meta-analysis approach. A database of 55 papers describing 63 experiments was gathered; broilers were challenged by Eimeria species (E. acervulina, E. maxima, E. tenella, and mixed) and at least 2 variables among ADFI, ADG, and feed conversion ratio (FCR) were studied. The variation induced by the challenge was calculated relative to the control group of each experiment. The indirect factors evaluated were days postinfection (DPI), Eimeria type and dose, infection age (IA), bird's mean age in the analyzed period, genetic line, sex, and whether they were raised in a cage or a pen. Graphical, correlation, and variance analyses were performed to evaluate the form of the responses. Then, a linear plateau model was adjusted for each response variable as a function of DPI to determine the consequences of the disease on the variation of performance over time after infection. The impact of the infection challenge on the variation of performance vs. nonchallenge broilers was only impacted by DPI (P < 0.05). The adjustment of the data with the linear plateau model allows us to determine the host response to the coccidiosis disease at different stages. At 5 DPI (acute phase), ΔADFI, ΔADG, ΔG:F were of -19.0; -39.8, and -25.5, respectively. After almost 13 DPI birds achieved the recovery phase for all variables with Δ varying from -19 to -3.75% for ADFI, from -39.8 to -10.5% for ADG, and from -25.5 to -7.24% for G:F. The Eimeria impact was higher in ADG than ADFI in all periods due to Eimeria aggressive action form causing lesions in gut epithelial reducing the use of nutrients and energy. The results can be used as a quantitative approach to determine the consequences of Eimeria spp. on broiler performance., (Copyright © 2023. Published by Elsevier Inc.)

Objective: After becoming widespread during the COVID-19 pandemic, telemedicine continues to play an important role in outpatient neurosurgical care. Nevertheless, the factors that influence individual decisions to choose telemedicine versus in-person appointments remain understudied. Here, we performed a prospective survey of pediatric neurosurgical patients and caregivers presenting for telemedicine or in-person outpatient visits, to identify factors associated with appointment choice., Methods: All patients and caregivers with an outpatient pediatric neurosurgical encounter at Connecticut Children's between January 31st and May 20th, 2022, were invited to participate in this survey. Data related to demographics, socioeconomics, technological access, COVID-19 vaccination status, and appointment preferences were collected., Results: During the study period, there were 858 unique pediatric neurosurgical outpatient encounters (86.1% in-person and 13.9% telemedicine). A total of 212 (24.7%) respondents completed the survey. Those with a telemedicine appointment were more likely to be white (P = 0.005), not Hispanic or Latino (P = 0.020), have private insurance (P = 0.003), be established patients (P < 0.001), have a household income >$80,000 (P = 0.005), and have caregivers who completed a 4-year college degree (P < 0.001). Those who were seen in-person cited the patient's condition, quality of care, and communication as important factors, whereas those who were seen via telemedicine cited time, travel, and convenience., Conclusions: While convenience influences some to choose telemedicine, concerns regarding the quality of care persist among those who prefer in-person encounters. Recognizing these factors will minimize barriers to care, better define the appropriate populations/contexts for each encounter type, and improve the integration of telemedicine within an outpatient neurosurgical setting., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Annular and acral/facial dyskeratotic paraneoplastic disorders are inflammatory dermatoses that occur in association with distant cancers but are not precursors, extensions, or metastases of them. There are four classical entities under this rubric: two gyrate entities, erythema annulare centrifugum and erythema gyratum repens, and two acral/facial dyskeratotic entities, acrokeratosis paraneoplastic (Bazex syndrome) and tripe palms. Each of these entities may also occur in association with another etiopathogenesis and may present either as a classical entity or as a barely recognizable disease. We discuss these entities, their associated causes, and their differential diagnoses in turn., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

The effect of Eimeria on apparent retention (AR) of components and metabolizable energy corrected for nitrogen (AMEn) content in corn, wheat, soybean meal (SBM), and pork meal (PM) was investigated in broiler chickens. A total of 840 male d-old Ross 708 chicks were placed in 84 cages (10 birds/cage) and allocated either a nitrogen-free diet (NFD), or 1 of 6 test cornstarch-based semipurified diets: 1) corn, 2) wheat, 3) SBM, 4) PM, 5) corn, SBM, and PM (CSP) mixture, and 6) wheat, SBM, and PM (WSP) mixture (n = 12). Diets contained 0.3% titanium dioxide and nutrient digestibility was determined by difference method using NFD. On d 10, birds in half of replicates per diet were orally challenge with 1 mL of E. acervulina and E. maxima culture and the other half equal volume of saline. Excreta samples were collected from d 12 to 14. With exception of AR of Ca and P, there was no interaction (P > 0.05) between Eimeria and diet on AR of dry matter, crude fat (CF), crude protein and gross energy and AMEn of ingredients. Eimeria reduced AR of CF (P = 0.01) and had a tendency to reduce AR of DM (P = 0.09) and AMEn (P = 0.063) of ingredients. The data demonstrated exposure to Eimeria impacted nutrient retention and energy utilization irrespective to diet composition., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The effect of Eimeria challenge on standardized ileal digestibility (SID) of amino acids (AA) in major poultry feed ingredients fed to broiler chickens was determined. A total of 840 male 9-day-old Ross 708 chicks were placed in 84 cages (10 birds/cage) and allocated to either a nitrogen-free diet (NFD) or one of the 6 test diets based on a single or mixture of feed ingredients as the sole source of AA (n = 12). Test diets were: 1) corn, 2) wheat, 3) soybean meal (SBM), 4) pork meal (PM), 5) corn, SBM, and PM (CSP), and 6) wheat, SBM, and PM (WSP). On d 10, birds in 6 cages/diet were orally gavaged with 1 mL of E. acervulina and E. maxima mixture and the other 6 cages with sham. On d 15, birds were bled for plasma AA and necropsied for intestinal lesion scores and ileal digesta samples. Challenge decreased (P < 0.05) plasma concentration of Arg, His, Thr, Asp, Gln, and Tyr and increased concentration of Lys, Ile, Leu, and Val. There was a diet by challenge interaction (P < 0.05) on intestinal lesion scores with birds fed mixed diets exhibiting more severe lesions than birds fed single ingredient diets. Diet by challenge interacted (P < 0.05) on ileal total endogenous flow (ITEF) of AA except for Arg, Met, Ala, Asp, and Cys, such that challenged birds fed the mixed, particularly WSP, had higher ITEF of AA compared to single ingredients birds. Diet and challenge interaction (P < 0.05) was observed for SID of Arg, Thr, Val, Glu, and Gly. Challenge decreased (P < 0.05) SID of most AA except for Met, Asp, and Cys with the largest impact seen on Lys, His, Ser, and Thr. With exception of Arg, Thr, Asp, and Cys, birds fed mixed diets had higher (P < 0.05) SID values compared to birds fed single ingredients. In conclusion, Eimeria reduced plasma availability and ileal digestibility of most AA. However, challenge interaction with diet composition on SID of some AA warrants further investigations., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The growing demand for high-value animal protein must be met using sustainable means that optimize the utilization of nutrients, especially nitrogen (N) so that excreta do not over-fertilize fields and end up causing soil acidification, waterway eutrophication and greenhouse gas emissions. Malodorous N compounds can cause respiratory diseases and poor growth in livestock. The increasing availability of feed-grade amino acids makes it possible to formulate low-protein diets for broilers and thereby reduce N excretion. However, published studies of the effects of such diets on broiler growth performance have been based on reducing CP contents gradually in a variety of ways that have given inconsistent results. Since the amount of published data is now large, a meta-analysis was performed in order to categorize diet formulation strategies and quantify their impact on N balance, water consumption, litter moisture, plasma uric acid. This showed that lowering the CP content of broiler diets generally means replacing some soybean meal with corn and hence increasing the starch content. However, since soybean meal is also a source of potassium, this reduces electrolyte balance. Lowering the CP content from 19% to 17% is associated with a 29% reduction of N excretion in broilers aged 0-21 d, and a 7% increase in N efficiency (N retention/N intake). Reducing the CP content from 19% to 17% decreases daily water consumption by 20.6 mL/bird, litter moisture by 2.2% and plasma uric acid by 0.56 mg/dL. This meta-analysis improves our understanding of the low-protein strategy and allows us to quantify its impact on N balance, litter quality and uric acid. It shows that managing N excretion is wholly beneficial and reduces litter wetness., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Eimeria infections impair digestive tract capacity and barrier function leading to poor growth and feed efficiency. A meta-analysis approach was used to evaluate and quantify impact of Eimeria infection on the apparent ileal digestibility (AID) of amino acids (AA) in broiler chickens. A database composed of 6 articles with a total of 21 experiments was built for the effect of challenge type (a mix of Eimeria spp. vs. E. acervulina) and subdatabase of 3 articles with a total of 15 experiments for the effect of E. acervulina dose response. Regression models were fitted with the mixed model procedure in Minitab 19 with fixed effects of challenge, species, and their interactions. For the sub database, the mixed model procedure was used to fit regression models and identify a linear or quadratic response to dose. Challenge decreased AID (P < 0.05) of both dispensable and indispensable AA except for Trp. Specifically, the largest depression was observed for Cys, Thr, Tyr, Ala, and Val with the magnitude of difference of 8.7, 5.4, 5.2, 5.1, and 4.9%, respectively for challenged vs. unchallenged birds. The type of challenge affected (P < 0.05) AID of AA with exception of Cys, Tyr, Ala, Ser, Leu, Asp, Gly, and Pro. E. acervulina challenge had larger negative effects on AID of Ile, Leu, and Val. Moreover, E. acervulina linearly decreased (P < 0.05) AID of all indispensable and dispensable AA except for Trp and quadratically (P < 0.05) decreased AID of all AA except Cys, Met, Arg, and Trp. The largest linear decrease due to E. acervulina dose was seen for AID of Cys, followed by Ala, Val, Thr, and Ile. Although, AID of Trp was not affected by E. acervulina challenge, mixed Eimeria species challenge decreased (P < 0.05) AID of Trp. Overall, the results confirmed that an Eimeria infection negatively impacted AA digestibility/utilization. The ranking of the most affected AA suggested ground for nutritional intervention during subclinical field Eimeria infections or vaccination programs., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

We investigatd the influence of do-not-resuscitate (DNR) status on mortality of hospital inpatients who died of COVID-19. This is a retrospective, observational cohort study of all patients admitted to two New Jersey hospitals between March 15 and May 15, 2020, who had, or developed, COVID-19 (1270 patients). Of these, 640 patients died (570 [89.1%] with and 70 [10.9%] without a DNR order at the time of admission) and 630 survived (180 [28.6%] with and 450 [71.4%] without a DNR order when admitted). Among the 120 patients without COVID-19 who died during this interval, 110 (91.7%) had a DNR order when admitted. Deceased positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients were significantly more likely to have a DNR order on admission compared with recovered positive SARS-CoV-2 patients (P < 0.05), similar to those who tested negative for SARS-CoV-2. COVID-19 DNR patients had a higher mortality compared with COVID-19 non-DNR patients (log rank P < 0.001). DNR patients had a significantly increased hazard ratio of dying (HR 2.2 [1.5-3.2], P < 0.001) compared with non-DNR patients, a finding that remained significant in the multivariate model. The risk of death from COVID-19 was significantly influenced by the patients' DNR status., Competing Interests: Conflict of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The novel coronavirus SARS-CoV-2 has caused coronavirus disease-2019, known as COVID-19, now a pandemic stressing millions of individuals worldwide. COVID-19 is a systemic respiratory infection that may have dermatologic signs and systemic sequelae, a devastating public health challenge with parallels to the two great influenza pandemics of the last century. Skin lesions linked with COVID-19 have been grouped into six categories, with three distinct indicative patterns: vesicular (varicella-like), vasculopathic, and chilblains-like (including "COVID toes" and "COVID fingers") plus the following three less suggestive patterns: dermatitic, maculopapular, and urticarial morphologies. Vasculopathic changes are the most concerning, in some patients, reflecting a devastating blood clotting dysfunction. We discuss the ways to detect, prevent, and treat COVID-19, keeping in mind the context of possible cutaneous markers of COVID-19 to enhance detection., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The coronavirus disease 2019 pandemic has had a profound effect on our lives and careers; this presentation explores some of the lessons we have learned from it and others that it may yet teach us. Socioeconomic effects have been profound, not all of them favorable. Travel and meeting activities, as well as many other activities, have been severely restricted. Social unrest has become intense, and it may have questionable political consequences, as the United States is undergoing a contested election result., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Climate change, sea-level rise, and human activities present major concerns for coastal environments. Paleoenvironmental records allow us to extend the instrumented record and study recent environmental impacts in a long-term context with natural pre-industrial conditions. Here, we investigate grain size, stable carbon (δ 13 C) and nitrogen (δ 15 N) isotopes, elemental composition, and diatom abundance in sediments to construct a 7000-year paleoenvironmental history of Weeks Bay, Alabama, a NOAA National Estuarine Research Reserve. Four major floods of the Fish River since 1986 CE are independently identified in the Weeks Bay sediment record, validating the bay setting as an archive of flood events. Thirty-four flood events were identified over the last 5000 years, with two periods of intense flood activity coinciding with the Medieval Climate Anomaly and the Little Ice Age, indicating association of relatively short-term climate events and enhanced storm activity. Further, multiple paleoenvironmental proxies indicate marine conditions during formation of the bay ~6600 calendar years Before Present (cal yr BP) and a brackish transition as the estuary became restricted ~2000 cal yr BP. High total organic carbon/nitrogen values indicate nitrogen limitation in Weeks Bay. Increase in organic content, diatoms, and redox- and nutrient-associated elemental proxies over the last 300 years, with dramatic increase in algal abundance since the 1980s, strongly suggest that human activities (i.e. land clearing, agriculture) increased ecological feedbacks in the bay. Comparing past and present environmental conditions of coastal estuaries advances our understanding of estuarine response to climate change and sea level, floods, and human activities, which is important for environmental management and wetland conservation policy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Although pityriasis alba is a common dermatologic condition, its pathogenesis is poorly understood, and there are many discrepancies in the literature. To assess the effect of the duration of disease on the histologic findings, a search of cases labeled "pityriasis alba" was performed on any cases submitted to our dermatopathology laboratory. Of 179 cases of pityriasis alba, five cases identified the duration of the disease, when the biopsy was taken. A biopsy for a lesion of only 1-month duration demonstrated groups of large, prominent melanocytes heaped up upon one another. Compared with biopsies from patients who had the lesions for increasingly longer periods of time, it was apparent that the melanocytes became progressively less abundant and smaller with less prominent dendritic processes. The time that the biopsy is taken may affect the histologic findings of pityriasis alba. Additionally, an abundance of melanosomes was observed between the melanocytes in all sections examined which may reflect a problem with the transfer of melanosomes into keratinocytes in this condition., (Copyright © 2019. Published by Elsevier Inc.)

Red color is pervasive in local and systemic skin conditions. It is a color that often reflects variations of dermal blood flow and extends beyond the rubor and calor of inflammation. The pathophysiology of red skin involves remote and local chemical mediators that dilate arteriolar smooth muscle and increase blood flow to superficial vessels and capillary beds. Incident light hits hemoglobin, which preferentially absorbs light of shorter wavelengths, such as blue, and reflects warmer colors. Due to its pervasiveness and consistency, red color is a useful descriptive factor in helping narrow a differential diagnosis. Red skin disorders include a variety of conditions involving endocrine mediators, cardiovascular responses, and the disruption of the skin barrier. An understanding of the blood's role in these disorders equips clinicians to generate differential diagnoses through the lens of pathophysiology. Dermatologists can improve management by considering red skin as part of systemic disease rather than as an isolated incident., (Copyright © 2019. Published by Elsevier Inc.)

Eumelanin is the major pigment responsible for human skin color. This black/brown pigment is localized in membrane-bound organelles (melanosomes) found in specialized cells (melanocytes) in the basal layer of the epidermis. This review highlights the steps involved in melanogenesis in the epidermis and the disorders in skin pigmentation that occur when specific steps critical for this process are defective. Melanosomes, which contain tyrosinase, a major enzyme involved in melanin synthesis, develop through a series of steps in the melanocyte. They are donated from the melanocyte dendrites to the surrounding keratinocytes in the epidermis. In the keratinocytes, the melanosomes are found singly or packaged into groups, and as the keratinocytes move upward in the epidermis, the melanosomes start to degrade. This sequence of events is critical for melanin pigmentation in the skin and can be influenced by genetic, hormonal, and environmental factors, which all play a role in levels of melanization of the epidermis. The effects these factors have on skin pigmentation can be due to different underlying mechanisms involved in the melanization process leading to either hypo- or hyperpigmentary disorders. These disorders highlight the importance of mechanistic studies on the specific steps involved in the melanization process., (Copyright © 2019. Published by Elsevier Inc.)

In order to control and optimize chicken quality products, it is necessary to improve the description of the responses to dietary amino acid (AA) concentration in terms of carcass composition and meat quality, especially during the finishing period. The aim of this study was to investigate the effects of Lysine (Lys, i.e. a limiting AA used as reference in AA nutrition) and AA other than Lys (AA effect). In total, 12 experimental diets were formulated with four levels of digestible Lys content (7, 8.5, 10 and 11.5 g/kg) combined with either a low (AA-), adequate control (AAc) and high (AA+) amount of other essential AA (EAA) expressed as a proportion of Lys. They were distributed to male Ross PM3 from 3 to 5 weeks of age. No significant AA×Lys interaction was found for growth performance or carcass composition. Body weight and feed conversion ratio were significantly improved by addition of Lys but were impaired in broilers receiving the AA- diets, whereas breast meat yield and abdominal fat were only affected by Lys. No additional benefit was found when the relative amount of other EAA was increased. There was a significant AA×Lys interaction on most of the meat quality traits, including ultimate pH, color and drip loss, with a significant effect of both AA and Lys. For example, AA- combined with reduced Lys level favored the production of meat with high ultimate pH (&gt;6.0), dark color and low drip loss whereas more acid, light and exudative meat (&lt;5.85) was produced with AA+ combined with a low Lys level. In conclusion, growth performance, carcass composition and meat quality are affected by the levels of dietary Lys and AA in finishing broilers. In addition, interactive responses to Lys and AA are found on meat quality traits, leading to great variations in breast pHu, color and drip loss according AA balance or imbalance.

Lowering protein level in diets for piglets urge to have knowledge on the piglet's requirements for essential amino acids (AA) and their interactions. The present studies aimed to determine the interaction between the dietary level of valine (Val) and tryptophan (Trp) and the effect of AA imbalance at two levels of dietary Val on the growth performance of post-weaning piglets. In Experiment 1 (duration 4 weeks), the effects of supplementation of free l-Val (1.0 g/kg) and/or l-Trp (0.5 g/kg) in a low-CP diet (CP 17.7%), marginal in Trp and Val, was studied in a 2×2 factorial design and using an additional reference treatment (CP 19.5%). In Experiment 2 (duration 5 weeks), the influence of a stepwise increase in excess supply of isoleucine (Ile), histidine (His) and leucine (Leu), up to 10, 10% and 30% relative to their requirement values respectively, was evaluated at 60% or 70% standardized ileal digestible (SID) Val relative to SID lysine, using a 3×2 factorial design. In Experiment 1, over the whole experimental period, feed intake (FI) was affected by dietary Trp level (P&lt;0.05) and feed conversion ratio (FCR) by both the level of Trp and Val in the diet (both P&lt;0.05). Increasing Trp level increased FI and decreased FCR while increasing dietary Val level reduced FI and increased FCR. For BW gain (BWG), there was an interaction between dietary level of Trp and Val (P&lt;0.05). Valine supplementation decreased BWG using a diet marginal in Trp, whereas it increased BWG when using a Trp sufficient diet. Piglets fed the low-CP diet with adequate levels of Val and Trp showed at least same performance compared to piglets fed the high CP reference diet. In Experiment 2, increasing dietary Val improved FI and BWG (P&lt;0.001) and tended to improve FCR. Dietary AA excess for Ile, His and Leu reduced FI and BWG (P&lt;0.05) and only affected FCR (P&lt;0.01) in the 1st week of the study. Dietary level of Val and AA excess did not show interactive effects, except for FCR over the final 2 weeks of the study (P&lt;0.05). In conclusion, an interaction exists between dietary supply of Val and Trp on the zootechnical performance of post-weaning piglets and dietary AA excess for Ile, Leu and His, reduces growth performance of piglets in low-protein diets, independent of the dietary level of Val.

Reducing the dietary CP content is an efficient way to limit nitrogen excretion in broilers but, as reported in the literature, it often reduces performance, probably because of an inadequate provision in amino acids (AA). The aim of this study was to investigate the effect of decreasing the CP content in the diet on animal performance, meat quality and nitrogen utilization in growing-finishing broilers using an optimized dietary AA profile based on the ideal protein concept. Two experiments (1 and 2) were performed using 1-day-old PM3 Ross male broilers (1520 and 912 for experiments 1 and 2, respectively) using the minimum AA:Lys ratios proposed by Mack et al. with modifications for Thr and Arg. The digestible Thr (dThr): dLys ratio was increased from 63% to 68% and the dArg:dLys ratio was decreased from 112% to 108%. In experiment 1, the reduction of dietary CP from 19% to 15% (five treatments) did not alter feed intake or BW, but the feed conversion ratio was increased for the 16% and 15% CP diets (+2.4% and +3.6%, respectively), while in experiment 2 (three treatments: 19%, 17.5% and 16% CP) there was no effect of dietary CP on performance. In both experiments, dietary CP content did not affect breast meat yield. However, abdominal fat content (expressed as a percentage of BW) was increased by the decrease in CP content (up to +0.5 and +0.2 percentage point, in experiments 1 and 2, respectively). In experiment 2, meat quality traits responded to dietary CP content with a higher ultimate pH and lower lightness and drip loss values for the low CP diets. Nitrogen retention efficiency increased when reducing CP content in both experiments (+3.5 points/CP percentage point). The main consequence of this higher efficiency was a decrease in nitrogen excretion (-2.5 g N/kg BW gain) and volatilization (expressed as a percentage of excretion: -5 points/CP percentage point). In conclusion, this study demonstrates that with an adapted AA profile, it is possible to reduce dietary CP content to at least 17% in growing-finishing male broilers, without altering animal performance and meat quality. Such a feeding strategy could therefore help improving the sustainability of broiler production as it is an efficient way to reduce environmental burden associated with nitrogen excretion.

Objective: The objective was to determine if intrauterine pressure can distinguish bilateral tubal occlusion (BTO) from unilateral or bilateral tubal patency (TP) in women following a permanent contraception procedure., Study Design: We used a small inline pressure sensor to continuously monitor intrauterine pressure during hysterosalpingogram (HSG) in a cross-sectional study that enrolled women having HSGs for any indication. The primary outcome was the peak intrauterine pressure compared between women with BTO and TP as verified by HSG., Results: We enrolled 150 subjects, of which 111 (74.0%) provided usable pressure readings. Of these, 98/111 (88.3%) had TP, and 13 (11.7%) had BTO. There was no difference in peak intrauterine pressure for subjects with TP (mean 293.8±58.7 mmHg) compared to those with BTO (292.7±71.3 mmHg, p=.95). Among parous women, peak intrauterine pressure in subjects with BTO (311.9±78.0 mmHg) was higher but not significantly different from subjects with TP (282.7±49.2 mmHg, p=.20). In linear regression analysis, peak intrauterine pressure was not associated with age, body mass index, gravidity or having at least one prior live birth., Conclusions: Measurement of peak intrauterine pressure does not distinguish between women with patent and blocked fallopian tubes. This approach would not be clinically useful to verify occlusion following permanent contraception., Implications: Peak intrauterine pressure does not differ between women with patent and occluded fallopian tubes and cannot be used to confirm tubal occlusion after nonsurgical permanent contraception., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Subcutaneous injection allows for self-administration of monoclonal antibodies using prefilled syringes, autoinjectors, and on-body injector devices. However, subcutaneous injections are typically limited to 1 mL due to concerns of injection pain from volume, viscosity, and formulation characteristics. Back pressure can serve as an indicator for changes in subcutaneous mechanical properties leading to pain during injection. The purpose of this study was to investigate subcutaneous pressures and injection site reactions as a function of injection volume and flow rate. A pressure sensor in the fluid path recorded subcutaneous pressures in the abdomen of Yorkshire swine. The subcutaneous tissue accommodates large-volume injections and with little back pressure as long as low flow rates are used. A 1 mL injection in 10 seconds (360 mL/h flow rate) generated a pressure of 24.0 ± 3.4 kPa, whereas 10 mL delivered in 10 minutes (60 mL/h flow rate) generated a pressure of 7.4 ± 7.8 kPa. After the injection, the pressure decays to 0 over several seconds. The subcutaneous pressures and mechanical strain increased with increasing flow rate but not increasing dose volume. These data are useful for the design of injection devices to mitigate back pressure and pain during subcutaneous large-volume injection., (Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

A method for the quantification of ethyl glucuronide (EtG) and ethyl sulphate (EtS) in human urine is developed and fully validated according to international guidelines. Protein precipitation is used as sample preparation. During the development of the method on an UPLC-ESI-MS/MS system using a CSH C18 column, special attention was paid to reduce matrix effects to improve assay sensitivity and to improve detection of the second transition for EtS for specificity purposes. The method was linear from 0.1 to 10μg/mL for both analytes. Ion suppression less than 24% (RSD<15%) was observed for EtG and no significant matrix effect was measured for EtS. The recovery was around 80% (RSD<14%) for both compounds. This method provides good precision (RSDr and RSDt<10%) and bias (<15%) for internal and external quality control samples. The reproducibility of the method was demonstrated by the successful participation to proficiency tests (z-score<0.86). This method was finally used to analyze urine samples obtained from twenty-seven volunteers whose alcohol consumption during the 5 days before sampling was monitored. Concentrations between 0.5 and 101.9μg/mL (mean 10.9, median 1.4) for EtG and between 0.1 and 37.9μg/mL (mean 3.6, median 0.3) for EtS were detected in urine samples of volunteers who declared having consumed alcohol the day before the sampling. EtG and EtS concentrations in urine were highly correlated (r=0.996, p<0.001). A moderate correlation between the number of drinks the day before sampling and the concentration of EtG (r=0.448, p<0.02) or EtS (r=0.406, p<0.04) was observed. Using a cut-off value at 0.1μg/mL for EtG and EtS, this method is able to detect social alcohol consumption approximately 24h after the intake, without showing any false positive result., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Small heat-shock protein chaperones are important players in the protein quality control system of the cell, because they can immediately respond to partially unfolded proteins, thereby protecting the cell from harmful aggregates. The small heat-shock proteins can form large polydisperse oligomers that are exceptionally dynamic, which is implicated in their function of protecting substrate proteins from aggregation. Yet the mechanism of substrate recognition remains poorly understood, and little is known about what parts of the small heat-shock proteins interact with substrates and what parts of a partially unfolded substrate protein interact with the small heat-shock proteins. The transient nature of the interactions that prevent substrate aggregation rationalize probing this interaction by crosslinking mass spectrometry. Here, we used a workflow with lysine-specific crosslinking and offline nano-liquid chromatography matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry to explore the interaction between the plant small heat-shock protein Hsp21 and a thermosensitive model substrate protein, malate dehydrogenase. The identified crosslinks point at an interaction between the disordered N-terminal region of Hsp21 and the C-terminal presumably unfolding part of the substrate protein.

Biofortification, that is, improving the micronutrient content of staple foods through crop breeding, could be a pro-poor, pro-rural, agriculture-based intervention to reduce the health burden of micronutrient malnutrition. While the potential cost-effectiveness of crops biofortified with single micronutrients was shown in previous research, poor people often suffer from multiple micronutrient deficiencies, which should be accounted for in biofortification initiatives. This study is the first to estimate the potential health benefits and cost-effectiveness of multi-biofortification. Rice with enhanced provitamin A, zinc, iron and folate concentrations is used as a concrete example. The research is conducted for China, the largest rice producer in the world, where micronutrient malnutrition remains a major public health problem. Using the DALY (disability-adjusted life year) framework, the current annual health burden of the four micronutrient deficiencies in China is estimated at 10.6 million DALYs. Introducing multi-biofortified rice could lower this burden by up to 46%. Given the large positive health impact and low recurrent costs of multi-biofortification, this intervention could be very cost effective: under optimistic assumptions, the cost per DALY saved would be around US$ 2; it would stay below US$ 10 even under pessimistic assumptions., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Cytosolic HPPK/DHPS (cytHPPK/DHPS) in Arabidopsis is a functional enzyme with activity similar to its mitochondrial isoform. Genomic complementation of the cytHPPK/DHPS knockout mutant with the wild type gene led to a complete rescue of the stress sensitive mutant phenotype in seed germination tests under abiotic stress conditions. Moreover, over-expression of the gene resulted in higher germination rate under stress as compared to the wild-type, confirming its role in stress resistance. Analysis of folates in seedlings, inflorescence and dry seeds showed unchanged levels in the wild-type, mutant and over-expressor line, upon stress and normal conditions, suggesting a role for cytHPPK/DHPS distinct from folate biosynthesis and a folate-independent stress resistance mechanism. This apparently folate-independent mechanism of stress resistance points towards a possible role of pterins, since the product of HPPK/DHPS is dihydropteroate., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Commonly used dermatologic eponyms and characteristic skin signs are enormously helpful in guiding a diagnosis, even though they may not be pathonemonic. They include, on the nails, Aldrich-Mees' lines (syn.: Mees' lines), Beau's lines, Muehrcke's lines, Terry's nails, and half and half nails, often associated, respectively, with arsenic poisoning, acute stress or systemic illness, severe hypertension, liver disease and uremia, and, around the nails, Braverman's sign, associated with collagen-vascular disease. Elsewhere, one may see the Asboe-Hansen and Nikolsky's signs, indicative of the pemphigus group of diseases, Auspitz's sign, a classic finding in psoriasis, Borsieri's and Pasita's signs, seen in early scarlet fever, the butterfly rash, indicative of systemic lupus erythematosus, and the buffalo hump, seen in Cushing's disease and also in the more common corticosteroid toxicity. Gottron's papules and the heliotrope rash are signs of dermatomyositis. Janeway's lesions and Osler's nodes are seen in bacterial endocarditis. A Dennie-Morgan fold under the eye is seen in association with atopic disease. Koplik's spots are an early sign of rubeola. Fitzpatrick's sign is indicative of a benign lesion (dermatofibroma), whereas Hutchinson's sign is indicative of a malignant one (subungual melanoma). Petechiae are seen in many diseases, including fat embolization, particularly from a large bone fracture following trauma. Palpable purpura is indicative of leukocytoclastic vasculitis, and is an early, critical sign in Rickettsial diseases, including Rocky Mountain Spotted Fever, which must be diagnosed and treated early. Hyperpigmentation of areolae and scars is seen in Addison's disease. Acanthosis nigricans may indicate internal cancer, especially stomach cancer, whereas Bazex's syndrome occurs in synchrony with primary, usually squamous cancer, in the upper aerodigestive tract or metastatic cancer in cervical lymph nodes. Perioral pigmented macules or one or more cutaneous sebaceous neoplasms may be a sign of the Peutz-Jeghers or Muir-Torre syndrome, respectively, both associated also with intestinal polyps that have a malignant potential. Telangiectasiae in the perioral region may be associated with similar lesions internally in Osler-Weber-Rendu disease. Kerr's sign is indicative of spinal cord injury and Darier's sign of mastocytosis. Post proctoscopic periobital purpura (PPPP) is a phenomenon observed in some patients with systemic amyloidosis. Koebner's isomorphic response refers to the tendency of an established dermatosis, such as psoriasis, to arise in (a) site(s) of trauma, whereas Wolf's isotrophic response refers to a new dermatosis, such as tinea, not yet seen in the patient, arising in (a) site(s) of a former but different dermatosis, such as zoster., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Dermatologic eruptions can be generalized or localized to specific areas of the body. Eruptions in specific body regions may suggest specific diagnosis. Recognizing such clinical patterns can facilitate the identification of the underlying pathology. In this contribution, we shall discuss those dermatologic lesions that tend to affect the flexure and extensor surfaces., (Copyright © 2011. Published by Elsevier Inc.)

Common shapes encountered in dermatologic diseases include linear, nummular, annular, polycyclic, and arciform. The last three have a relatively restricted differential, which must be entirely explored. It is not uncommon for a single disease to present in annular, arciform or polycyclic configurations; moreover, the lesions may evolve from being arciform to annular and then become polycyclic. Regardless, recognizing the arrangement of the defect will undoubtedly help in making a diagnosis and guiding subsequent management. We explore diseases that often present in annular, arciform, and/or polycyclic forms., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To report the case of a 48-year-old African American man with lentigo maligna of the left lower eyelid., Design: Interventional case report., Participants: One patient with lentigo maligna of the left lower eyelid., Methods: We report the clinical presentation, histopathologic and immunohistochemical features, and treatment of an African American man with lentigo maligna of the eyelid. The current literature regarding this uncommon neoplasm in African American patients also is reviewed., Main Outcome Measures: Histopathologic and immunohistochemical diagnosis and clinical evaluation for recurrence., Results: An excisional biopsy revealed lentigo maligna. An extensive literature search revealed no definitive reports of lentigo maligna or lentigo maligna melanoma of the eyelid in an African American patient., Conclusions: Although extremely rare, lentigo maligna may involve ocular adnexal skin in African Americans. Awareness and recognition of this premalignant lesion will aid in early diagnosis and treatment and eventually may improve prognosis.

Bowenoid papulosis (BP) is a condition triggered by human papillomavirus infection and characterized by the development of 1 or more warty lesions, usually in the anogenital region. Although the oral cavity has been known to host several types of warts, thus far only 4 cases of BP have been reported in this anatomic site. We describe a 42-year-old male with AIDS who presented with numerous papillary lesions of the labial mucosa and vermilion. Biopsy yielded a diagnosis of BP. Treatment of the condition consisted of intralesional and subcutaneous injections of interferon-alpha followed by topical application of imiquimod 5% cream. Neither regimen resulted in resolution of the lesions. To our knowledge, this represents the first case of BP arising in the oral mucosa of an HIV-infected individual.

Background: Reference values of numerous micronutrients at different gestational ages (GA) have not been yet reported based on large series., Aims: This study aimed to establish the reference range for zinc, copper, selenium, vitamin A, vitamin E, retinol binding protein, transthyretin, albumin, transferrin and ceruloplasmin in neonates and to give the profiles according to gestational age., Study Design: A total of 510 infants appropriate for gestational age were included in the study. The determinations were done using the serum cord blood of 262 term and 248 preterm infants (gestational age of 37 to 42 and 26 to 36 weeks, respectively)., Results: All nutrients correlated significantly with birth weight and gestational age but different patterns were highlighted. Vitamin A, retinol binding protein and prealbumin showed a triphasic pattern with a cut-off at about 36 to 39 weeks. In this period, these parameters rised significantly (P<0.001). Albumin and selenium showed a biphasic pattern with a significant positive correlation (P<0.001) between weeks 26 to 38. Transferrin and ceruloplasmin associated with copper showed a continuous increase with GA (P<0.001). On the opposite, zinc and vitamin E decreased. Zinc showed a biphasic pattern with a significant negative correlation (P<0.001) between the 26th to 34th weeks. Vitamin E presented a triphasic pattern with a cut-off at about 32 to 35 weeks (P<0.001)., Conclusion: The large number of data allow the build-up of reference ranges and charts for the evaluation of micronutrients and proteins in high-risk neonates.

Purpose: The objective of this study was to investigate whether the knowledge of genetics relevant for daily practice among medical students nearing graduation in the Netherlands was sufficient to react appropriately to the change of relevance of genetics in medicine., Methods: A computer examination validated in a group of clinical geneticists, medical students nearing graduation, and nonmedical students. The examination consisted of 215 genetic questions classified by the designers into three categories of relevance: "essential" knowledge (requirement: > 95% correct answers), "desirable" knowledge (requirement: > 60% correct answers), and "too specialized" knowledge (no requirement). To set an independent standard, the questions were also judged by clinical geneticists and nongenetic health care providers in an Angoff procedure. In total, 291 medical students nearing graduation from seven out of the eight medical schools in the Netherlands participated., Results: As expected, the mean score for "essential" knowledge (71.63%, 95% CI 70.74-72.52) was higher than for "desirable" knowledge (55.99%, 95% CI 55.08-56.90); the mean score for "too specialized" knowledge (44.40%, 95% CI 43.19-45.62) was the lowest. According to passing scores set for "essential" knowledge as defined by the designers, the clinical geneticists, and the nongenetic health care providers, only 0%, 26%, and 3%, respectively, of the participants would have passed., Conclusions: Medical students nearing graduation lack genetic knowledge that is essential for daily practice. Therefore, changes should be made in the medical curricula.

In recent years, despite the increasing success of liquid chromatography (LC) coupled to tandem mass spectrometry (MS), reports on matrix susceptibility have shown the limitations of the this powerful analytical technique. Matrix effects (MEs) result from co-eluting residual matrix components affecting the ionization efficiency of target analytes and can lead to erroneous results. The present work evaluates the matrix effect of environmental water samples on 35 endocrine disrupting chemicals (EDCs) in negative and positive LC-ESI-MS/MS. It was shown that mobile-phase additives could significantly influence matrix effects. Addition of acids resulted in a severe signal suppression (average ME%: <65%), and 1 mM ammonium formate increased the average ME% to 84%. The importance of an efficient sample clean-up and internal standardization also was demonstrated. Cleaner extracts resulted in reduced matrix effects (average ME%: 89%) and labeled internal standards proved to have a beneficial effect especially on signal reproducibility (average CV% 4.2% versus 2.6%). The results from the present work indicate that evaluation of matrix effects should become an integrated part of quantitative LC-ESI-MS/MS method development and validation.

Background: Nutrition education is not an integral part of either undergraduate or postgraduate medical education. Computer-based instruction on nutrition might be an attractive and appropriate tool to fill this gap., Objective: The study objective was to assess the degree to which computer-based instruction on nutrition improves factual knowledge and practice behavior of general practitioner (GP) trainees., Design: We carried out a controlled experimental study, using a 79-item knowledge test and 3 incognito standardized patients' visits in a pre- and posttest design with 49 first-year GP trainees. The experimental group (n = 25) received an average of 6 h of a newly developed computer-based instruction on nutrition. The control subjects (n = 24) took the standard vocational training program., Results: The percentage of correct answers on the knowledge test increased from 30% at pretest to 42% at posttest in the experimental group, and from 36% to 37% in the control group. Analysis of covariance, with the pretest scores as covariate, showed a significant experimental versus control group difference at posttest: 9.2% (P = 0.002). The mean percentage of correctly performed items during the 3 standardized patients' visits (assessed by checklists) showed an increase in the experimental group from 20% at pretest to 36% at posttest, whereas the control group changed from 20% to 22%. Analysis of covariance, with the pretest scores as covariate, revealed a significant group difference at posttest: 13.7% (P < 0.001)., Conclusion: The computer-based instruction proved its effectiveness, both by increasing factual knowledge and by substantially enhancing GP trainees' practice behavior on the subject of nutrition.

A fast liquid chromatographic method with tandem diode array-fluorescence detection for the simultaneous determination of in total 17 opium alkaloids and opioids is presented. Blank blood and urine samples (1 ml) were spiked with different concentrations of a standard mixture, as well as with the internal standard, butorphanol (2000 ng/ml). After solid-phase extraction, based on weak cation exchange (Bond Elut CBA SPE columns), the extracts were examined by HPLC-DAD-FL. By using a "high-speed" phenyl column (53 x 7.0 mm I.D., particle size 3 microm) eluted with a gradient system (A: water-methanol (90:10, v/v), B: methanol, both containing 25 mM triethylammoniumformate (pH(A) = 4.5)) all compounds could be baseline separated within 12 min. The method was validated and its applicability was demonstrated by the analysis of real-time forensic cases.

A gas chromatographic-mass spectrometric method was developed for the simultaneous analysis of 15 low-dosed benzodiazepines, both parent compounds and their corresponding metabolites, in human urine. The target compounds are alprazolam, alpha-hydroxyalprazolam, 4-hydroxyalprazolam, flunitrazepam, 7-aminoflunitrazepam, desmethylflunitrazepam, flurazepam, hydroxyethylflurazepam, nitrogen-desalkylflurazepam, ketazolam, oxazepam, lormetazepam, lorazepam, triazolam and alpha-hydroxytriazolam. Nitrogen-methylclonazepam is used as the internal standard. The urine sample preparation involves enzymatic hydrolysis of the conjugated metabolites with Helix pomatia beta-glucuronidase for 1 h at 56 degrees C followed by solid-phase extraction on a phenyl-type column. The extracted benzodiazepines are subsequently analyzed on a polydimethylsiloxane column using on-column injection to enhance sensitivity. The extraction efficiency exceeded 80% for all compounds except for oxazepam, lorazepam and 4-hydroxyalprazolam which had recoveries of about 60%. The LODs ranged from 13 to 30 ng/ml in the scan mode and from 1.0 to 1.7 ng/ml in the selected ion monitoring (SIM) mode. Linear calibration curves were obtained in the concentration ranges from 50 to 1000 ng/ml in the scan mode and from 5 to 100 ng/ml in the SIM mode. The within-day and day-to-day relative standard deviations at three different concentrations never exceeded 15%.

Stir bar sorptive extraction (SBSE) on polydimethylsiloxane (PDMS) was applied to the enrichment of polychlorinated biphenyls (PCBs) from human sperm. The seven Ballschmiter PCBs were used as model compounds. The extracted PCBs were then thermally desorbed from the stir bar and analysed on-line by capillary gas chromatography (CGC) with mass spectrometric detection (MS). Method development started with the analysis of PCBs spiked in water. Methanol had to be added to the samples in order to reduce the influence of glass adsorption on recovery and reproducibility. Recoveries in water for all PCBs varied around 50-60% and were limited for low molecular mass (MM) PCBs by polarity changes in the sample due to methanol addition and for high MM PCBs by non-equilibrium conditions. Matrix suppression by the lipophilic medium lowered the recoveries in the sperm samples proportional with PCB polarity. The method was validated and although limits of detection (LOD) for the individual congeners were in the sub-ppt level (

GC-MS screening conditions were developed for 15 low-dosed benzodiazepines, covering alprazolam, flunitrazepam, flurazepam, ketazolam, lorazepam and triazolam, and the corresponding metabolites alpha-hydroxyalprazolam, 4-hydroxyalprazolam; 7-aminoflunitrazepam, desmethylflunitrazepam, 7-aminodesmethylflunitrazepam; hydroxyethylflurazepam, N-desalkylflurazepam; oxazepam and alpha-hydroxytriazolam, respectively. Benzodiazepines are analyzed on a polydimethylsiloxane column in both the scan and the multiple ion monitoring modes using on-column injection to attain maximal sensitivity. The reactive compounds are acetylated with pyridine and acetic anhydride for 20 min. The derivatives are stable for at least 4 days. The relative standard deviation observed with standard compounds at the low nanogram-level ranged from 1.13 to 4.87% within-day and from 1.12 to 4.94% between-day. Unequivocal identification potential, high chromatographic resolution and sensitivity are combined with minimal thermal degradation. The presented screening conditions provide the basis for a unique routine screening method for low-dosed benzodiazepines with a broad polarity range.

We report a precise and reliable method for the detection of 18 of the most commonly found opiates on the Belgian legal and illicit market, by ion-exchange, reversed-phase high-performance liquid chromatography, using a conventional phenyl-type analytical column (150x4.6 mm I.D., particle size 5 microm) and diode-array detection. We also describe a performance (efficiency and sensitivity) comparison of this column to a recently developed "high-speed" column (53x7.0 mm I.D., particle size 3 microm) packed with the same stationary phase, and used under slightly adjusted flow and gradient conditions. The final method, using the "high-speed" column, showed a significant reduction (55%) in analysis time without loss of resolution and sensitivity.