Management of maternal pulse and blood pressure abnormalities during labour and childbirth: evidence-based algorithms for intrapartum care decision support.

AIMS: To develop evidence-based clinical algorithms for assessment and management of abnormal maternal pulse and blood pressure during the intrapartum period. POPULATION: Low risk singleton, term, pregnant women in labour. SETTING: Institutional births in low- and middle-income countries. SEARCH STRATEGY: A review of the literature was performed to retrieve evidence-based guidelines, systematic reviews, and papers on maternal pulse and blood pressure during labour. We searched a number of international clinical guidelines and PubMed using the corresponding key terms in November 2018 and updated the search in May 2020. CASE SCENARIOS: Four common intrapartum case scenarios of abnormal pulse and blood pressure were identified for which algorithms were developed: hypertension, hypotension, tachycardia and bradycardia. Algorithms were constructed after reviewing guidelines and relevant papers, with input from a panel of experts. Thresholds for upper and lower limits of normal maternal pulse and blood pressure measurements are defined, evidence-based interventions for the initial management of abnormal parameters are described (resuscitation and monitoring) and guidance is provided on exploration of the potential causes for each case scenario, with links to pathways for their management. CONCLUSIONS: Evidence-based algorithms to support the identification, and management of deviations in pulse and blood pressure during intrapartum care have been developed for hypertension, hypotension, tachycardia and bradycardia. The algorithms focus on initial resuscitation and monitoring, with an exploration of causes and early identification of underlying maternal conditions. These algorithms will help provide a standardised approach to investigation and management of these abnormal parameters to guide clinical practice. TWEETABLE ABSTRACT: Algorithms for abnormal maternal pulse and blood pressure during labour allow standardised approach to early identification and management of complications.

A Robust Handwritten Numeral Recognition Using Hybrid Orthogonal Polynomials and Moments.

Numeral recognition is considered an essential preliminary step for optical character recognition, document understanding, and others. Although several handwritten numeral recognition algorithms have been proposed so far, achieving adequate recognition accuracy and execution time remain challenging to date. In particular, recognition accuracy depends on the features extraction mechanism. As such, a fast and robust numeral recognition method is essential, which meets the desired accuracy by extracting the features efficiently while maintaining fast implementation time. Furthermore, to date most of the existing studies are focused on evaluating their methods based on clean environments, thus limiting understanding of their potential application in more realistic noise environments. Therefore, finding a feasible and accurate handwritten numeral recognition method that is accurate in the more practical noisy environment is crucial. To this end, this paper proposes a new scheme for handwritten numeral recognition using Hybrid orthogonal polynomials. Gradient and smoothed features are extracted using the hybrid orthogonal polynomial. To reduce the complexity of feature extraction, the embedded image kernel technique has been adopted. In addition, support vector machine is used to classify the extracted features for the different numerals. The proposed scheme is evaluated under three different numeral recognition datasets: Roman, Arabic, and Devanagari. We compare the accuracy of the proposed numeral recognition method with the accuracy achieved by the state-of-the-art recognition methods. In addition, we compare the proposed method with the most updated method of a convolutional neural network. The results show that the proposed method achieves almost the highest recognition accuracy in comparison with the existing recognition methods in all the scenarios considered. Importantly, the results demonstrate that the proposed method is robust against the noise distortion and outperforms the convolutional neural network considerably, which signifies the feasibility and the effectiveness of the proposed approach in comparison to the state-of-the-art recognition methods under both clean noise and more realistic noise environments.

[Professional profiles and representations of staff members in Burundi health centers: Socio-professional groups with compartmentalizes knowledge]. / Profils et représentations professionnelles des agents en centre de santé au Burundi : des groupes socio-professionnels aux savoirs cloisonnés.

BACKGROUND: The professional identities, profiles and representations of Burundian health workers remain insufficiently explored. Our twofold objective is to identify the different socio-professional profiles of first-line caregivers and to explore their respective representations of health workers and work. METHODS: The first study describes the overall population of the 1047 staff members employed in 2014-2015 in 62 health centers. The second is a cross-sectional survey conducted in April 2014. Using IRAMUTEQ© software, we conducted textology analysis of the structure and contents of 911 respondents' representations via 3 free associations with regard to 6 questions on the "good worker" and the "what renders one capable of doing good work". RESULTS: At the normative level, among all categories of staff, a relational role is a foundation of professional identity, while technical or administrative functions remain marginal. At the positional level, responses differed according to initial qualification level but not as a function of their role with patients or their professional experience. Three socio-professional categories emerged. The most qualified category (one-quarter of the population) consists primarily of male caregivers, with a high turnover rate (4 years) associated with prospects for further training and career development. These persons present the most professionalized representations of the worker and work. The second quarter has an average level of qualification and turnover (10 years), and is mainly composed of female caregivers with limited professional perspectives. This group's representations are less technical and more patient-centered. Finally, the remaining half consists of relatively low-skilled staff members in charge of technical and logistical support, who are likely to spend their entire career in the same center (>20 years). Largely disregarded by the health care system and its funders, they have few opportunities for training or advancement and despite their long experience, maintain profane representations of workers and work. CONCLUSION: Our results shed light on the predicament of unskilled staff members whose expectations are rarely taken into consideration, even though they represent a significant proportion of the workforce, perform tasks essential to quality of care, and serve as bearers of the memory of their hospital center. These results also highlight the compartmentalization of practices and knowledge between categories of workers and underscore the failure of continuous training strategies targeting the unskilled.

Effect of red blood cell preservation by droplet freezing with non-permeable cryoprotective agents in blood group antigen reactivity.

BACKGROUND: In the last few decades, various red blood cell (RBC) freezing techniques have been developed and improved to enable the preservation of erythrocytes for future use in pre-transfusion tests in reference immunohaematology laboratories. However, not all these techniques have been sufficiently evaluated for the preservation of blood group antigens. OBJECTIVES: In this study, we evaluated the antigenic pattern of RBCs preserved by droplet freezing in liquid nitrogen in a blood bank context. METHODS: Blood samples were evaluated for the reactivity of blood group antigens after droplet freezing using the non-permeable cryoprotective agent polyvinylpyrrolidone (PVP) and sucrose-dextrose (S + D) solutions. RESULTS: No qualitative changes were observed in RBC reactivity after freezing and thawing for the antigens Fyb , Leb , C, E, Cw , Lua , Lub , Kpa , Kpb and Dia . However, cryopreservation using PVP resulted in a significant increase in reactivity of Fyb antigen on comparing fresh and frozen samples (P < 0·001). CONCLUSION: The establishment of detailed protocols for cryopreservation of RBCs, which take into account the maintenance of antigenic characteristics, is necessary to increase security in pre-transfusion testing using frozen RBCs.

The role of infection and sepsis in the Brazilian Network for Surveillance of Severe Maternal Morbidity.

OBJECTIVE: To identify the burden of severe infection within the Brazilian Network for Surveillance of Severe Maternal Morbidity and factors associated with worse maternal outcomes. METHODS: This was a multicentre cross-sectional study involving 27 referral maternity hospitals in Brazil. WHO's standardised criteria for potentially life-threatening conditions and maternal near miss were used to identify cases through prospective surveillance and the main cause of morbidity was identified as infection or other causes (hypertension, haemorrhage or clinical/surgical). Complications due to infection were compared to complications due to the remaining causes of morbidity. Factors associated with a severe maternal outcome were assessed for the cases of infection. RESULTS: A total of 502 (5.3%) cases of maternal morbidity were associated with severe infection vs. 9053 cases (94.7%) with other causes. Considering increased severity of cases, infection was responsible for one-fourth of all maternal near miss (23.6%) and nearly half (46.4%) of maternal deaths, with a maternal near miss to maternal death ratio three times (2.8:1) that of cases without infection (7.8:1) and a high mortality index (26.3%). Within cases of infection, substandard care was present in over one half of the severe maternal outcome cases. Factors independently associated with worse maternal outcomes were HIV/AIDS, hysterectomy, prolonged hospitalisation, intensive care admission and delays in medical care. CONCLUSIONS: Infection is an alarming cause of maternal morbidity and mortality and timely diagnosis and adequate management are key to improving outcomes during pregnancy. Delays should be addressed, risk factors identified, and specific protocols of surveillance and care developed for use during pregnancy.

Severe maternal morbidity due to respiratory disease and impact of 2009 H1N1 influenza A pandemic in Brazil: results from a national multicenter cross-sectional study.

BACKGROUND: The aim of this study was to assess the burden of respiratory disease, considering the influenza A pandemic season (H1N1pdm09), within the Brazilian Network for Surveillance of Severe Maternal Morbidity, and factors associated with worse maternal outcome. METHODS: A multicenter cross-sectional study, involving 27 referral maternity hospitals in five Brazilian regions. Cases were identified in a prospective surveillance by using the WHO standardized criteria for potentially life-threatening conditions (PLTC) and maternal near miss (MNM). Women with severe complications from respiratory disease identified as suspected or confirmed cases of H1N1 influenza or respiratory failure were compared to those with other causes of severe morbidity. A review of suspected H1N1 influenza cases classified women as non-tested, tested positive and tested negative, comparing their outcomes. Factors associated with severe maternal outcome (SMO = MNM + MD) were assessed in both groups, in comparison to PLTC, using PR and 95 % CI adjusted for design effect of cluster sampling. RESULTS: Among 9555 cases of severe maternal morbidity, 485 (5 %) had respiratory disease. Respiratory disease occurred in one-quarter of MNM cases and two-thirds of MD. H1N1 virus was suspected in 206 cases with respiratory illness. Around 60 % of these women were tested, yielding 49 confirmed cases. Confirmed H1N1 influenza cases had worse adverse outcomes (MNM:MD ratio < 1 (0.9:1), compared to 12:1 in cases due to other causes), and a mortality index > 50 %, in comparison to 7.4 % in other causes of severe maternal morbidity. Delay in medical care was associated with SMO in all cases considered, with a two-fold increased risk among respiratory disease patients. Perinatal outcome was worse in cases complicated by respiratory disease, with increased prematurity, stillbirth, low birth weight and Apgar score < 7. CONCLUSIONS: Respiratory disease, especially considering the influenza season, is a very severe cause of maternal near miss and death. Increased awareness about this condition, preventive vaccination during pregnancy, early diagnosis and treatment are required to improve maternal health.

Network for Surveillance of Severe Maternal Morbidity: a powerful national collaboration generating data on maternal health outcomes and care.

OBJECTIVE: To identify cases of severe maternal morbidity (SMM) during pregnancy and childbirth, their characteristics, and to test the feasibility of scaling up World Health Organization criteria for identifying women at risk of a worse outcome. DESIGN: Multicentre cross-sectional study. SETTING: Twenty-seven referral maternity hospitals from all regions of Brazil. POPULATION: Cases of SMM identified among 82 388 delivering women over a 1-year period. METHODS: Prospective surveillance using the World Health Organization's criteria for potentially life-threatening conditions (PLTC) and maternal near-miss (MNM) identified and assessed cases with severe morbidity or death. MAIN OUTCOME MEASURES: Indicators of maternal morbidity and mortality; sociodemographic, clinical and obstetric characteristics; gestational and perinatal outcomes; main causes of morbidity and delays in care. RESULTS: Among 9555 cases of SMM, there were 140 deaths and 770 cases of MNM. The main determining cause of maternal complication was hypertensive disease. Criteria for MNM conditions were more frequent as the severity of the outcome increased, all combined in over 75% of maternal deaths. CONCLUSIONS: This study identified around 9.5% of MNM or death among all cases developing any severe maternal complication. Multicentre studies on surveillance of SMM, with organised collaboration and adequate study protocols can be successfully implemented, even in low-income and middle-income settings, generating important information on maternal health and care to be used to implement appropriate health policies and interventions. TWEETABLE ABSTRACT: Surveillance of severe maternal morbidity was proved to be possible in a hospital network in Brazil.

Genome-wide association study of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 ancestry-matched controls and 400 complete trios remained, with a common set of 469,410 autosomal and 9657 X-chromosome single nucleotide polymorphisms (SNPs). Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two P-values were located within DLGAP1 (P=2.49 × 10(-6) and P=3.44 × 10(-6)), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a P-value=3.84 × 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 × 10(-5), losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation QTLs (P<0.001) and frontal lobe expression quantitative trait loci (eQTLs) (P=0.001) was observed within the top-ranked SNPs (P<0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD.

A novel N-input voting algorithm for X-by-wire fault-tolerant systems.

Voting is an important operation in multichannel computation paradigm and realization of ultrareliable and real-time control systems that arbitrates among the results of N redundant variants. These systems include N-modular redundant (NMR) hardware systems and diversely designed software systems based on N-version programming (NVP). Depending on the characteristics of the application and the type of selected voter, the voting algorithms can be implemented for either hardware or software systems. In this paper, a novel voting algorithm is introduced for real-time fault-tolerant control systems, appropriate for applications in which N is large. Then, its behavior has been software implemented in different scenarios of error-injection on the system inputs. The results of analyzed evaluations through plots and statistical computations have demonstrated that this novel algorithm does not have the limitations of some popular voting algorithms such as median and weighted; moreover, it is able to significantly increase the reliability and availability of the system in the best case to 2489.7% and 626.74%, respectively, and in the worst case to 3.84% and 1.55%, respectively.

A novel clustering algorithm for mobile ad hoc networks based on determination of virtual links' weight to increase network stability.

The stability of clusters is a serious issue in mobile ad hoc networks. Low stability of clusters may lead to rapid failure of clusters, high energy consumption for reclustering, and decrease in the overall network stability in mobile ad hoc network. In order to improve the stability of clusters, weight-based clustering algorithms are utilized. However, these algorithms only use limited features of the nodes. Thus, they decrease the weight accuracy in determining node's competency and lead to incorrect selection of cluster heads. A new weight-based algorithm presented in this paper not only determines node's weight using its own features, but also considers the direct effect of feature of adjacent nodes. It determines the weight of virtual links between nodes and the effect of the weights on determining node's final weight. By using this strategy, the highest weight is assigned to the best choices for being the cluster heads and the accuracy of nodes selection increases. The performance of new algorithm is analyzed by using computer simulation. The results show that produced clusters have longer lifetime and higher stability. Mathematical simulation shows that this algorithm has high availability in case of failure.

[Pragmatism and realism for public health intervention evaluation]. / Pragmatisme et réalisme pour l'évaluation des interventions de santé publique.

Forty years ago, Schwartz and Lellouch invented pragmatic clinical trials. Their proposal has not yet been fully espoused. This appears to be the case today also in the domain of public health interventions evaluation, where some still insist on the superiority of experimental methods. Yet evaluations of complex public health interventions are fraught with pitfalls for researchers. Most such interventions take place in natural experimental contexts, where they have no control over the context or the factors that modify implementation and influence the effects. Experimental approaches are, in these cases, not very appropriate, and yet decision makers want to be able to take decisions to improve them. This article presents our experience over the past 5years with evaluative research in two public health interventions. We wish to show how we conduct evaluations in practice using a pragmatic approach. The article is focused on elements that have not, to date, received much attention in the francophone literature: the evaluability assesment and intervention logic, research strategies reinforced particularly by mixed methods and time series, and the analysis of implementation fidelity and mechanisms that foster effectiveness. Because the pragmatic approach to evaluative research stresses the need for good understanding of context and uses reinforced methodological strategies, it allows for rigorous responses to evaluation questions raised by those implementing complex public health interventions. Thus, experimental approaches are not necessarily required to analyze the effectiveness of interventions.

Revision anterior cruciate ligament reconstruction and outcomes with different autografts in a population with kneeling customs.

OBJECTIVES: This study was designed to evaluate, compare the mid-term functional outcome of revision anterior cruciate ligament reconstruction (ACLR) using different autografts and assess the cause of failure of primary ACLR in an Omani population with kneeling customs. MATERIALS AND METHODS: Patients with failed primary ACLR who underwent revision ACLR using autografts were included in this retrospective study. The cause of primary ACLR failure and the functional outcome was assessed using the Tegner-Lyholm knee score and compared among bone patella tendon-bone (BPTB), quadriceps tendon (QT), semitendinosus gracilis (STG) autografts used. RESULTS: One hundred two patients (102 male) were included in the study with a minimum follow-up of 2 years. Thirty-one patients underwent revision with BPTB, 34 with STG and 19 with QT autografts. Majority of the patients (70.23%) achieved good-to-excellent functional outcome based on their Tegner-Lysholm scores. The functional outcome of different autografts was comparable to each other based on Kruskal-Wallis test. The causes of primary ACLR failure were failure due to trauma in 58.33% of patients, technical failure in 22.61% of patients, and nontraumatic failure in 19.04% of patients. CONCLUSIONS: The functional outcome of revision ACLR in this Middle Eastern Asian Omani population was good-to-excellent, with the patients experiencing no difficulty in performing activities of daily living, including kneeling activities. The outcome of different autografts, BTPB, QT, STSG is similar in high knee flexion patients with no autograft found to be superior. The findings of this study add to the literature on functional outcomes after primary and revision ACLR in a customary kneeling population.

Performance of Nursing Awassi Ewes Fed Different Levels of Bread By-product.

Objective of this experiment was to evaluate the effect of partial substitution of barley grain with bread by-product (BB) on performance of Awassi ewes and their lambs. Forty Awassi ewes rearing single lambs were randomly allotted into four experimental diets containing various levels of BB. The experimental diets contained 0 (BB0), 10 (BB10), 15 (BB15), and 20% (BB20) of BB on dietary dry matter (DM). The study lasted for eight weeks, in which the first week was used as an adaptation period and seven weeks of data collection. Ewes and their lambs were penned individually where they were fed their lactating diets ad libitum. Ewes and lambs body weights were measured at the beginning and at the end of the experiment. However, milk production and composition were evaluated biweekly. Feeding BB had no effect (p>0.05) on dry matter (DM), organic matter (OM), and crude protein (CP) intakes. However, neutral detergent fiber (NDF) intake was the lowest (p<0.05) for the BB20 and BB15 diets followed to BB10 diet (i.e., 640, 677, 772 g/d, respectively) while the highest NDF intake was for the BB0 diet (i.e., 825 g/d). Similarly, NDF intake decreased linearly (p<0.001) as the BB content increased. Acid detergent fiber (ADF) intake was highest (p<0.05) for the BB0 and BB10 diets (425 and 416 g/d, respectively) followed by the BB15 and BB20 diets (359 and 342 g/d, respectively). Moreover, a linear (p<0.001), quadratic (p = 0.04), and cubic (p = 0.04) effects were observed in ADF intake among diets. Nutrient digestibility was similar among different diets. Bread by-product had no effect (p>0.05) on ewes body weight change and on lamb performance (i.e., weaning body weight and average daily gain). Similarly, no differences (p>0.05) were observed either in milk production or composition by the BB substitution. Inclusion of BB reduced feed cost by 9, 14, and 18% for the BB10, BB15, and BB20 diets, respectively. No differences were observed in milk efficiency (DM intake: milk production; p>0.05) among diets. However, cost of milk production ($US/kg milk) was the lowest (p<0.05) in the diet containing BB20. Results of the present study indicate that feeding bread by-product up to 20% of the diet DM had no effect on performance of Awassi ewes and their lambs and reduced feed cost.

Arthroscopic treatment for intra-articular adhesions of the temporomandibular joint.

PURPOSE: To introduce arthroscopic surgery of intra-articulator adhesion of the temporomandibular joint (TMJ) upper compartment and evaluate its effect. PATIENTS AND METHODS: One hundred forty-two patients (159 joints) with intra-articular adhesions confirmed by arthroscope were treated with lysis of the adhesions, intra-articular cleanup surgery, or capsule radiofrequency catheter ablation. One hundred ten patients (123 joints) with disc displacement were treated with the disc repositioning and suturing technique. The follow-up index includes jaw movement, visual analog scale pain value, and patients' self-evaluation. The therapeutic effect was divided into excellent, good, and poor. Excellent and good patients were defined as effective. Jaw movement and visual analog scale pain value before and after the operation were evaluated by a paired t test. RESULTS: The average follow-up period was 10.3 months (range: 2-27 months), and 33.80% (48/142) of all joints were excellent; 56.34% (80/142) were good, and 9.86% (14/142) were poor. The total effectiveness rate was 90.14% (128/142). Of all patients, 93.66% (133/142) felt more comfortable than they had before the operation. The interincisal opening increased from a preoperative 23.14 ± 5.93 mm (range: 10-40 mm) to postoperative 37.48 ± 3.51 mm (range: 30-40 mm; P < .01), and the pain scores were reduced from 28.94 ± 23.54 (0-80) to 4.44 ± 10.10 (0-40; P < .05). CONCLUSION: The effect of arthroscopic surgery on temporomandibular joint intra-articular adhesion was positive. It can increase the mouth's range of motion, improve jaw function, and reduce pain during jaw movement.

An overview of the literature on emerging pollutants: Chlorinated derivatives of Bisphenol A (ClxBPA).

CONTEXT: Bisphenol A (BPA) is a ubiquitous contaminant with endocrine-disrupting effects in mammals. During chlorination treatment of drinking water, aqueous BPA can react with chlorine to form chlorinated derivatives of BPA (mono, di, tri and tetra-chlorinated derivatives) or ClxBPA. OBJECTIVE: The aim of this study is to summarize and present the state of knowledge on human toxicological risk assessment of ClxBPA. MATERIALS AND METHODS: A search on ClxBPA in the PubMed database was performed based on studies published between 2002 and 2021. Forty-nine studies on chlorinated derivatives of BPA were found. Available information on their sources and levels of exposure, their effects, their possible mechanisms of action and their toxicokinetics data was extracted and presented. RESULTS: ClxBPA have been essentially detected in environmental aqueous media. There is evidence in toxicological and epidemiological studies that ClxBPA also have endocrine-disrupting capabilities. These emerging pollutants have been found in human urine, serum, breast milk, adipose and placental tissue and can constitute a risk to human health. However, in vitro and in vivo toxicokinetic data on ClxBPA are scarce and do not allow characterization of the disposition kinetics of these compounds. CONCLUSION: More research to assess their health risks, specifically in vulnerable populations, is needed. Some water chlorination processes are particularly hazardous, and it is important to evaluate their chlorination by-products from a public health perspective.

Native valve endocarditis complicated by abscess formation caused by Rothia mucilaginosa.

Rothia mucilaginosa is increasingly recognized as an emerging pathogen associated with endocarditis. It has mostly been reported a causative agent for prosthetic valve endocarditis. The previously reported cases of native valve endocarditis caused by this organism only required medical treatment with no surgical intervention. We report a case of R. mucilaginosa native valve endocarditis complicated by abscess formation requiring surgical intervention and review the literature of native valve endocarditis caused by this organism.

Eye of the Tiger Sign in Pantothenate Kinase-Associated Neurodegeneration.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare disorder associated with brain iron accumulation caused by a recessive mutation in pantothenate kinase 2 gene (PANK2). We present a case of an 11 year-old boy presenting extrapyramidal signs and developmental regression. T2-weighted images showed the classic eye of the tiger sign seen in pantothenate kinase-associated neurodegeneration.

High concentrations of commonly used drugs can inhibit the in vitro glucuronidation of bisphenol A and nonylphenol in rats.

4-n-Nonylphenol and bisphenol A are endocrine disrupting chemicals that are mainly detoxified through glucuronidation. A factor that may modulate their glucuronidation rates is co-exposure to pharmaceuticals. This study aimed to identify and characterize the potential metabolic interactions between 14 drugs and these two endocrine disruptors. Nonylphenol and bisphenol A were co-incubated in freshly isolated rat hepatocytes with, drugs at a high concentration. Statistically significant metabolic inhibition of bisphenol A and nonylphenol biotransformation was observed with nine drugs (>50% inhibition by naproxen, salicylic acid, carbamazepine and mefenamic acid). Inhibition assays of UGT activity in rat liver microsomes revealed: 1) competitive inhibition by naproxen (K(i)(app) = 848.3 microM) and carbamazepine (K(i)(app) = 1023.1 microM), 2) no inhibition by salicylic acid suggesting another mechanism of inhibition. Detoxification of nonylphenol and bisphenol A was shown to be impaired by excessive concentrations of many drugs and health risk assessment should therefore address this issue.

Physiologically based modeling of p-tert-octylphenol kinetics following intravenous, oral or subcutaneous exposure in male and female Sprague-Dawley rats.

The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model for p-tert-octylphenol (OP) for understanding the qualitative and quantitative determinants of its kinetics in Sprague-Dawley rats. Compartments of the PBPK model included the liver, richly perfused tissues, poorly perfused tissues, reproductive tissues, adipose tissue and subcutaneous space, in which OP uptake was described as a blood flow- or a membrane diffusion-limited process. The PBPK model successfully simulated previously published data on blood and tissue OP concentrations in Sprague-Dawley rats following oral, intravenous (i.v.) or subcutaneous (s.c.) routes. The model predicted that OP concentrations would reach 6.8, 13.8 and 27.9 ng ml(-1) (male) and 7.2, 14.7 and 31.4 ng ml(-1) (female), 4 h after a single i.v. dose of 2, 4 and 8 mg kg(-1), respectively. The model also predicted that OP concentrations would reach 53.3, 134.8 and 271.2 ng ml(-1) (male) and 87.4, 221.4 and 449.7 ng ml(-1) (female) 4 h after a single oral dose (50, 125 and 250 mg kg(-1)) and that, 4 h after a single s.c. dose (125 mg kg(-1)), OP concentrations would reach 111.3 ng ml(-1) (male) and 121.6 ng ml(-1). A marked sex difference was seen in blood and tissue OP concentrations. This was reflected in the model by a gender-specific maximal velocity of metabolism (V(max)) that was higher (1.77 x) in male than in female rats. Further studies are required to elucidate the mechanism underlying the gender differences and to evaluate whether that is also observed in humans.

Encephalopathy and seizure activity in a COVID-19 well controlled HIV patient.

A 41-year-old male with a history of well controlled HIV presented with confusion and was found to have COVID-19. Lumbar puncture was negative. He had worsening encephalopathy with tonic-clonic seizure requiring intubation. He was treated with hydroxychloroquine and azithromycin with improvement in mental status back to baseline after 6 days.