Supramolecular solvents for making comprehensive liquid-liquid microextraction in multiclass screening methods for drugs of abuse in urine based on liquid chromatography-high resolution mass spectrometry.

Multiclass screening methods involving hundreds of structurally unrelated compounds are becoming essential in many control labs and research areas. Accurate mass screening of a theoretically unlimited number of chemicals can be undertaken using liquid chromatography coupled to high resolution mass spectrometry (LCHRMS), but the lack of comprehensive sample treatments hinders this unlimited potential. In this research, the capability of supramolecular solvents (SUPRAS) for making comprehensive liquid-liquid microextraction (LLME) in multiclass screening methods based on LCHRMS was firstly explored. For this purpose, a SUPRAS made up of 1,2-hexanediol, sodium sulphate and water was synthesized directly in the urine and applied to compound extraction and interference removal in the screening of eighty prohibited substances in sports by LC-electrospray ionization-time of flight mass spectrometry. Selected substances included a wide range of polarities (log P from -2.4 to 9.2) and functionalities (e.g. alcohol, amine, amide, carboxyl, ether, ester, ketone, sulfonyl, etc.). No interfering peaks were observed for any of the 80 substances investigated. Around 84-93% of drugs were efficiently extracted (recoveries 70-120%) and 83-94% of the analytes did not show matrix effects (±20%) in the ten tested urines. Method detection limits for the drugs were in the interval 0.002-12.9 ng mL-1, which are in accordance with the Minimum Required Performance Levels values established by the World Anti-Doping Agency. The applicability of the method was evaluated by the screening of thirty-six blinded and anonymized urine samples, previously analyzed by gas or liquid chromatography-triple quadrupole. Seven of the samples lead to an adverse analytical finding in line with the results obtained by the conventional methods. This research proves that LLME based on SUPRAS constitutes an efficient, economic, and simple sample treatment in multiclass screening methods, an application that is unaffordable for conventional organic solvents.

Performance of a Likert adaptation of the SRQ-20 scale among women victims of intimate partner violence in Colombia: an exploratory study.

Women who are victims of intimate partner violence often suffer of depression and anxiety disorders. We evaluated the performance of the SRQ-20 scale (screening test for common mental health disorders), in women victims of intimate partner violence by male partners. A total of 100 women were surveyed from the out-patient mental health services in four health institutions in Valle del Cauca (Colombia). SRQ-20 scales (Binary version versus Likert version) were compared with mental health diagnoses based on the HSCL-25 scale, as the gold standard. Optimal SRQ-20 cut-off score is > = 6 points; lower than the initially suggested, sensitivity of 96.6% and specificity of 90.9%. The new SRQ-20-Likert scale, establishing a cut-off of > = 8 points, shows better sensitivity (98.9%) and equal specificity than the original scale. Studied SRQ-20 scales are promising instruments for screening mental health disorders among women victims of intimate partner violence in primary health care settings.

Cubosomic Supramolecular Solvents: Synthesis, Characterization, and Potential for High-Throughput Multiclass Testing of Banned Substances in Urine.

This paper was intended to efficiently extract multiclass prohibited substances in human sport drug testing by using supramolecular solvents (SUPRASs) made up of cubosomes. These SUPRASs, here first reported, are synthesized by the salt-induced coacervation of 1,2-hexanediol in urine. The formation of square and rounded cubosomes with a size range of 140-240 nm was confirmed by electron microscopy. These nanostructures consisted of 1,2-hexanediol, salt, and a high water content (36-61%, w/w). Their applicability in multiclass determinations was investigated by the extraction of 92 prohibited substances (log P from 2.4 to 9.2) belonging to the 10 categories of the World Anti-Doping Agency's (WADA) list. Variables influencing both recoveries and matrix effects were optimized. Cubosomic SUPRASs showed high extraction efficiency and interference removal capability, which was attributed to their large hydrophilicity and surface area. Both features were superior to those of the other 11 SUPRASs that were based on sponge droplets and inverted hexagonal aggregates and to those of conventional organic solvents. A sport drug-testing method based on cubosomic SUPRAS-LC-ESI-MS/MS was proposed and validated. Around 82-95% of drugs were efficiently extracted (recoveries 70-120%) in urine samples, and 81-92% did not present matrix effects. The method detection limits (0.001-4.2 ng mL-1) were all far below WADA's limits. The proposed SUPRAS-based sample treatment is as simple as QuEChERS, but the distinctive features of cubosomes confer them high capability in multiclass determinations.

A qualitative study on factors associated with intimate partner violence in Colombia.

Intimate partner violence (IPV) is a human rights violation and a serious global public health problem. This study investigated factors associated with IPV in female survivors in Colombia. Four focus group discussions with female survivors of IPV and 15 key informant interviews with professionals from psychological, social and legal services and community leaders were conducted in Cali and Tuluá. Participant recruitment was via purposive sampling. Transcripts were analysed manually taking a social constructivist standpoint and a content analysis approach. Factors associated with IPV were divided into four themes: cultural beliefs, jealousy, alcohol abuse, and personal history of IPV. The first theme was divided into: patriarchy, gender roles, normalisation of violence, and unawareness of rights, economic dependence, and 'men own women'. The sub-themes were all inter-related and underpinned by patriarchal values. IPV was described as a sociocultural construction formed by patriarchal values ingrained in community and societal norms and individual processes. Therefore, academia, governmental and non-governmental bodies and society are urged to together, create preventative, context specific strategies for individuals, communities and societies.

A qualitative study on factors associated with intimate partner violence in Colombia

Abstract Intimate partner violence (IPV) is a human rights violation and a serious global public health problem. This study investigated factors associated with IPV in female survivors in Colombia. Four focus group discussions with female survivors of IPV and 15 key informant interviews with professionals from psychological, social and legal services and community leaders were conducted in Cali and Tuluá. Participant recruitment was via purposive sampling. Transcripts were analysed manually taking a social constructivist standpoint and a content analysis approach. Factors associated with IPV were divided into four themes: cultural beliefs, jealousy, alcohol abuse, and personal history of IPV. The first theme was divided into: patriarchy, gender roles, normalisation of violence, and unawareness of rights, economic dependence, and 'men own women'. The sub-themes were all inter-related and underpinned by patriarchal values. IPV was described as a sociocultural construction formed by patriarchal values ingrained in community and societal norms and individual processes. Therefore, academia, governmental and non-governmental bodies and society are urged to together, create preventative, context specific strategies for individuals, communities and societies.

Resumo A violência por parceiro íntimo (VPI) é uma violação dos direitos humanos e um grave problema de saúde pública global. Este estudo investigou fatores associados à VPI em mulheres sobreviventes na Colômbia. Quatro discussões de grupos focais com mulheres sobreviventes de VPI e 15 entrevistas com informantes-chave com profissionais de serviços sócio-médico-legais foram realizadas usando amostragem intencional nas cidades de Cali e Tuluá. As transcrições foram analisadas manualmente, sob um ponto de vista construtivista social e uma abordagem de análise de conteúdo. Os fatores associados à VPI foram divididos em 4 temas: crenças culturais, ciúmes, abuso de álcool e história pessoal da VPI. O primeiro tema foi dividido em: patriarcado, papéis de gênero, normalização da violência, desconhecimento de direitos, dependência econômica e 'homens possuem mulheres'. VPI foi descrita como uma construção sociocultural formada por valores patriarcais e processos individuais. A VPI é causada por uma complexa interação de diferentes fatores nos níveis do indivíduo, relacionamentos, comunidade e social. Os órgãos governamentais e não governamentais e a sociedade são instados a criar juntos estratégias preventivas e específicas no contexto.

Correction: Earl et al. Somatic Mutation Profiling in the Liquid Biopsy and Clinical Analysis of Hereditary and Familial Pancreatic Cancer Cases Reveals KRAS Negativity and a Longer Overall Survival. Cancers 2021, 13, 1612.

The authors wish to make the following corrections to this paper [...].

A comprehensive study on the performance of different retention mechanisms in sport drug testing by liquid chromatography tandem mass spectrometry.

Anti-doping substances listed by the World Anti-Doping Agency (WADA) include hundreds of compounds of very different physico-chemical properties. Anti-doping control laboratories need to screen all these substances in the so-called Initial Testing Procedures (ITPs) what is very challenging from an analytical point of view. ITPs are mostly based on reversed-phase (RP) liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) using C18 columns, which feature poor retention and peak tailing for polar and basic compounds, respectively. While studies on this field dealing with the comparison of stationary phases are focused on certain chemical classes, this research provides a wide multi-target approach. For this purpose, a representative group of 93 anti-doping agents (log P from -2.4 to 9.2) included in ten different classes of prohibited substances was selected. A comprehensive study on the performance of six columns and four eluents on different separation parameters (retention factors, asymmetry factors, co-elutions, total run times) and matrix effects (signal enhancement or suppression) was performed for LC-MS/MS-based ITPs. Columns working in both RP [C18, C8, phenyl hexyl (PH), pentafluorophenyl (PFP) and mixed-mode hydrophilic/RP (HILIC-RP)) and hydrophilic (HILIC)] modes were investigated. Eluents contained methanol or acetonitrile as organic modifiers, with or without the addition of ammonium acetate. The best column-mobile phase binomial for ITPs was PFP using water-methanol (0.1% formic acid) as eluent, while HILIC was the best option for highly polar non-aromatic anti-doping agents, which were poorly addressed by PFP. Excellent good peak shapes and relative acceptable matrix interferences were obtained for HILIC-RP, which was tested for the first time for the analysis of anti-doping agents, although the number of compounds eluting too fast was too high. On the whole, the alkyl phase C18 showed the worst performance and although C8 and PH were better, their performance did not surpass that of PFP. Possible retention mechanisms underlying separation in the different stationary phases were discussed. This research provides valuable information to anti-doping control labs for improving LC-MS/MS-based ITPs and it proposes PFP as a suitable alternative to the already established C18.

Somatic Mutation Profiling in the Liquid Biopsy and Clinical Analysis of Hereditary and Familial Pancreatic Cancer Cases Reveals KRAS Negativity and a Longer Overall Survival.

Pancreatic ductal adenocarcinoma (PDAC) presents many challenges in the clinic and there are many areas for improvement in diagnostics and patient management. The five-year survival rate is around 7.2% as the majority of patients present with advanced disease at diagnosis that is treatment resistant. Approximately 10-15% of PDAC cases have a hereditary basis or Familial Pancreatic Cancer (FPC). Here we demonstrate the use of circulating free DNA (cfDNA) in plasma as a prognostic biomarker in PDAC. The levels of cfDNA correlated with disease status, disease stage, and overall survival. Furthermore, we show for the first time via BEAMing that the majority of hereditary or familial PDAC cases (around 84%) are negative for a KRAS somatic mutation. In addition, KRAS mutation negative cases harbor somatic mutations in potentially druggable genes such as KIT, PDGFR, MET, BRAF, and PIK3CA that could be exploited in the clinic. Finally, familial or hereditary cases have a longer overall survival compared to sporadic cases (10.2 vs. 21.7 months, respectively). Currently, all patients are treated the same in the clinic with cytotoxic agents, although here we demonstrate that there are different subtypes of tumors at the genetic level that could pave the way to personalized treatment.

A case of inflammatory pseudotumour of the gallbladder presenting as a big mass of uncertain behavior.

BACKGROUND: Inflammatory pseudotumour has been used to describe an inflammatory or fibrosing tumoral process of an undetermined cause that may involve a variety of organ systems, including the lungs, spleen, liver, lymph nodes, pancreas and extrahepatic bile duct with potential for recurrence and persistent local growth. In this article, we report a patient with a big mass of uncertain nature and behavior. CASE PRESENTATION: A 60-year-old woman presented with a 1-week history of abdominal pain, fever and jaundice. Six months before she had had right upper quadrant pain that was interpreted as biliary colic. A contrast-enhanced CT scan showed a big mass of soft tissue with diffuse infiltration of the gallbladder, displacement of the transverse colon, hepatic flexure and duodenum. For diagnostic distinction between a chronic inflammatory disease or a neoplasm, exploratory laparotomy was required. Intraoperative exploration disclosed a big mass of hard texture involving the gallbladder, with multiple concrements, hepatoduodenal ligament, right and transverse mesocolon, stomach and duodenum. Cholecystectomy was performed, preserving adjacent organs with macroscopic desmoplastic reaction. Histopathologic examination of the gallbladder showed a spindle cell proliferation with diffuse chronic inflammatory infiltrate of lymphocytes, plasma cells and hyalinized fibrous stroma. No vascular invasion or cellular atypia were evident. CONCLUSION: Inflammatory pseudotumour is a rare condition and diagnostic distinction from a chronic inflammatory disease or other neoplasm is only possible by histopathologic examination. There is a limited number of case reports in the literature indicating tumor location in the gallbladder.

A comprehensive analysis of candidate genes in familial pancreatic cancer families reveals a high frequency of potentially pathogenic germline variants.

BACKGROUND: The 5-year survival rate of patients with pancreatic ductal adenocarcinoma (PDAC) is around 5% due to the fact that the majority of patients present with advanced disease that is treatment resistant. Familial pancreatic cancer (FPC) is a rare disorder that is defined as a family with at least two affected first degree relatives, with an estimated incidence of 4%-10%. The genetic basis is unknown in the majority of families although around 10%-13% of families carry germline mutations in known genes associated with hereditary cancer and pancreatitis syndromes. METHODS: Panel sequencing was performed of 35 genes associated with hereditary cancer in 43 PDAC cases from families with an apparent hereditary pancreatic cancer syndrome. FINDINGS: Pathogenic variants were identified in 19% (5/26) of PDAC cases from pure FPC families in the genes MLH1, CDKN2A, POLQ and FANCM. Low frequency potentially pathogenic VUS were also identified in 35% (9/26) of PDAC cases from FPC families in the genes FANCC, MLH1, PMS2, CFTR, APC and MUTYH. Furthermore, an important proportion of PDAC cases harboured more than one pathogenic, likely pathogenic or potentially pathogenic VUS, highlighting the multigene phenotype of FPC. INTERPRETATION: The genetic basis of familial or hereditary pancreatic cancer can be explained in 21% of families by previously described hereditary cancer genes. Low frequency variants in other DNA repair genes are also present in 35% of families which may contribute to the risk of pancreatic cancer development. FUNDING: This study was funded by the Instituto de Salud Carlos III (Plan Estatal de I + D + i 2013-2016): ISCIII (PI09/02221, PI12/01635, PI15/02101 and PI18/1034) and co-financed by the European Development Regional Fund ''A way to achieve Europe'' (ERDF), the Biomedical Research Network in Cancer: CIBERONC (CB16/12/00446), Red Temática de investigación cooperativa en cáncer: RTICC (RD12/0036/0073) and La Asociación Española contra el Cáncer: AECC (Grupos Coordinados Estables 2016).

Early detection of lysosomal diseases by screening of cases of idiopathic splenomegaly and/or thrombocytopenia with a next-generation sequencing gene panel.

Lysosomal diseases (LD) are a group of about 70 rare hereditary disorders (combined incidence 1:5000) in which diverse lysosomal functions are impaired, impacting multiple organs and systems. The first clinical signs and symptoms are usually unspecific and shared by hundreds of other disorders. Diagnosis of LD traditionally relies on performing specific enzymatic assays, if available, upon clinical suspicion of the disorder. However, the combination of the insidious onset of LD and the lack of awareness on these rare diseases among medical personnel results in undesirable diagnostic delays, with unchecked disease progression, appearance of complications and a worsened prognosis. We tested the usefulness of a next-generation sequencing-based gene panel for quick, early detection of LD among cases of idiopathic splenomegaly and/or thrombocytopenia, two of the earliest clinical signs observed in most LD. Our 73-gene panel interrogated 28 genes for LD, 1 biomarker and 44 genes underlying non-LD differential diagnoses. Among 38 unrelated patients, we elucidated eight cases (21%), five with LD (GM1 gangliosidosis, Sanfilippo disease A and B, Niemann-Pick disease B, Gaucher disease) and three with non-LD conditions. Interestingly, we identified three LD patients harboring pathogenic mutations in two LD genes each, which may result in unusual disease presentations and impact treatment. Turnaround time for panel screening and genetic validation was 1 month. Our results underline the usefulness of resequencing gene panels for quick and cost-effective screening of LDs and disorders sharing with them early clinical signs.

Urine Caffeine Concentration in Doping Control Samples from 2004 to 2015.

The ergogenic effect of caffeine is well-established, but the extent of its consumption in sport is unknown at the present. The use of caffeine was considered "prohibited" until 2004, but this stimulant was moved from the List of Prohibited Substances to the Monitoring Program of the World Anti-Doping Agency to control its use by monitoring urinary caffeine concentration after competition. However, there is no updated information about the change in the use of caffeine as the result of its inclusion in the Monitoring Program. The aim of this study was to describe the changes in urine caffeine concentration from 2004 to 2015. A total of 7488 urine samples obtained in official competitions held in Spain and corresponding to athletes competing in Olympic sports (2788 in 2004, 2543 in 2008, and 2157 in 2015) were analyzed for urine caffeine concentration. The percentage of samples with detectable caffeine (i.e., >0.1 µg/mL) increased from ~70.1%, in 2004⁻2008 to 75.7% in 2015. The median urine caffeine concentration in 2015 (0.85 µg/mL) was higher when compared to the median value obtained in 2004 (0.70 µg/mL; p < 0.05) and in 2008 (0.70 µg/mL; p < 0.05). The urine caffeine concentration significantly increased from 2004 to 2015 in aquatics, athletics, boxing, judo, football, weightlifting, and rowing (p < 0.05). However, the sports with the highest urine caffeine concentration in 2015 were cycling, athletics, and rowing. In summary, the concentration of caffeine in the urine samples obtained after competition in Olympic sports in Spain increased from 2004 to 2015, particularly in some disciplines. These data indicate that the use of caffeine has slightly increased since its removal from the list of banned substances, but urine caffeine concentrations suggest that the use of caffeine is moderate in most sport specialties. Athletes of individual sports or athletes of sports with an aerobic-like nature are more prone to using caffeine in competition.

Validity of self-reported indicators to assess secondhand smoke exposure in the home.

INTRODUCTION: Questionnaires are widely used to assess secondhand smoke (SHS) exposure. However, the validity of self-reported SHS exposure indicators has been rarely assessed. We aimed to assess correlations, sensitivity, specificity, and predictive values between self-reported SHS exposure indicators and airborne nicotine concentrations. METHODS: We performed a cross-sectional study with a convenience sample of 175 homes in Barcelona and Santiago de Compostela, Spain. Airborne nicotine samples were collected from participants' homes and a self-administered questionnaire was completed on SHS exposure in the home. Spearman correlations coefficients and sensitivity, specificity and predictive values were assessed between self-reported SHS exposure indicators and nicotine concentrations in the home. RESULTS: All self-reported SHS exposure indicators correlated moderately strongly with airborne nicotine concentrations (Spearman correlations coefficient ranging from 0.58 to 0.65). Moreover, sensitivities and negative predictive values between self-reported indicators and the presence of nicotine in the home were below 66.4% while specificities and positive predictive values were over 78.4%. The "number of people usually smoking in the home" showed the best results (rs = 0.65, p < 0.001; sensitivity = 50.4%, specificity = 95.2%, PPV = 95.0, NPV = 51.3). CONCLUSIONS: The self-reported SHS indicators assessed in this study showed moderate and strong correlations, low sensitivities, and high specificities. Among them, the best results were obtained with the "number of people usually smoking in the home".

Second-hand smoke exposure in homes with children: assessment of airborne nicotine in the living room and children's bedroom.

BACKGROUND: The introduction of 'smoke-free laws' has reduced the population's exposure to second-hand smoke (SHS), although SHS is still an issue in homes and other public places. Children are vulnerable to its health effects, and their greatest exposure occurs at home. OBJECTIVES: To assess airborne nicotine concentration of the living room and children's bedroom of homes with children under 13 years of age, and to analyse factors associated with these levels. METHODS: We conducted a cross-sectional study in Barcelona in 2015-2016, selecting a convenience sample from families with at least one child under 13 years of age. The sample comprised 50 families with smokers and 50 without. We measured airborne nicotine concentrations in the living room and children's bedroom, and, using a questionnaire administered to the parents, collected information about smoking habits at home. RESULTS: Homes without smokers showed nicotine concentrations below the limit of detection (<0.02 µg/m3), while those with at least one smoker showed 0.16 µg/m3 in the living room and 0.12 µg/m3 in the bedroom. When smoking was allowed inside home, these values increased to 1.04 and 0.48 µg/m3, respectively. Moreover, nicotine concentrations in both rooms were strongly correlated (r=0.89), and higher nicotine levels were associated with the number of cigarettes smoked in the living room, smoking rules, the number of smokers living at home and tobacco smell. CONCLUSIONS: Homes with smokers present SHS in the living room and in the children's bedroom. Therefore, programmes focused on reducing children's SHS exposure are urgently needed.

Cirugía de la hidatidosis hepática. Factores de riesgo y variables asociadas al desarrollo de morbilidad postoperatoria. Revisión global de la evidencia existente / Surgery for hepatic hidatidosis. Risk factors and variables associated with postoperative morbidity. Overview of the existing evidence

Las publicaciones relacionadas con morbilidad postoperatoria en hidatidosis hepática son escasas y de resultados disímiles. El objetivo de este estudio fue determinar factores de riesgo y protectores de morbilidad postoperatoria en pacientes intervenidos por hidatidosis hepática. Se realizó una revisión global de la evidencia, basada en revisiones sistemáticas, ensayos clínicos y estudios observacionales, obtenidos de Trip Database, BVS, SciELO, Cochrane Central Register of Controlled Trials, WoS, MEDLINE, EMBASE, SCOPUS, EBSCOhost, IBECS, ePORTUGUESe, LILACS y WHOLIS. Se identificaron 1.087 artículos relacionados y 69 cumplían criterios de selección (2 revisiones sistemáticas, 3 ensayos clínicos y 64 estudios observacionales). Se identificaron como factores de riesgo la edad, el antecedente de cirugía previa por hidatidosis hepática, la localización centro hepática, la existencia de comunicaciones biliares y complicaciones evolutivas del quiste y como protectores las técnicas quirúrgicas radicales. Se identificaron factores de riesgo y protectores; sin embargo, los estudios son escasos y de calidad moderada a baja (AU)

There are few publications related to postoperative morbidity in hepatic hydatidosis and these have mixed results. The aim of this study was to determine risk and protective factors of postoperative morbidity in patients operated on for hepatic hydatidosis. A comprehensive review was made of the evidence, based on systematic reviews, clinical analyses and observational studies, obtained from the Trip Database, BVS, SciELO, Cochrane Central Register of Controlled Trials, WoS, MEDLINE, EMBASE, SCOPUS, EBSCOhost, IBECS, ePORTUGUESe, LILACS and WHOLIS. 1,087 related articles were identified; 69 fulfilled the selection criteria (2 systematic reviews, 3 clinical trials and 64 observational studies). Age, history of previous surgery for hepatic hydatidosis, location in the hepatic center, existence of biliary communications and evolutionary complications of the cyst were identified as risk factors, and radical surgical techniques as protective factors. Risk and protective factors were identified; however, the studies are few and the quality moderate to low (AU)