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BackgroundSleep-disordered breathing (SDB) in pregnancy is associated with adverse maternal outcomes. The relationship between SDB and infant birthweight is unclear. This study's primary aim is to determine if objectively measured SDB in pregnancy is associated with infant birthweight.MethodsWe measured SDB objectively in early (6-15 weeks' gestation) and mid (22-31 weeks' gestation) pregnancy in a large cohort of nulliparous women. SDB was defined as an Apnea-Hypopnea Index ≥5 and in secondary analyses we also examined measures of nocturnal hypoxemia. We used a modified Poisson regression approach to estimate relative risks (RR) of large-for-gestational-age (LGA: >90th percentile for gestational age) and small-for-gestational-age (SGA

Objective To characterize the clinicopathologic findings, comorbidities, and treatment outcomes of women with lichen planopilaris (LPP). Method In this retrospective review of women with LPP at Mayo Clinic from 1992 to 2016, we searched for scarring alopecia in all female patients aged 1 to 100 years from January 1, 1992, through December 31, 2016. Men were excluded from this study to more accurately determine the association of hormonal factors in LPP pathogenesis. Two hundred thirty-two patients were included as they met diagnostic criteria for LPP based on clinicopathologic correlation, with 217 having confirmatory biopsies. Results We identified 232 women with LPP (mean age, 59.8 years). Of those, 92.7% (215) presented with hair loss; 23.7% (55) had preceding inflammation; 30.6% (71) had thyroid disease, including hypothyroidism (23.2%; 54); and 9.4% (22) had vitamin D deficiency. Incidence of depression and anxiety was 45.7% (106) and 41.8% (97), respectively. History of total abdominal hysterectomy/bilateral salpingo-oophorectomies and hormone replacement therapy was found in 16.8% (39) and 16.4% (38), respectively. Lichen planus at other body sites occurred in 16.4% (38) of patients; and 53.2% (123) had slowing of disease progression or disease stabilization, often requiring combination therapies. In those who achieved slowing or stabilization of disease, mean time to recurrence was 1.8 year. The mean time to remission was 1.1 year. Conclusion The typical LPP patient is a 60-year-old female with vertex scarring alopecia who presents with burning, erythema, inflammation, and scale. Almost half of patients will have comorbid autoimmunity. As previously reported, LPP is associated with thyroid disease. We also found higher rates of depression, anxiety, nutritional deficiencies, and skin cancer than reported in the general population.

The objective of the study was to evaluate the morbidity, mortality, and postoperative outcomes associated with simple or subcutaneous mastectomy in the management of prophylactic versus therapeutic resection. In this study we aimed to assess if simple or subcutaneous mastectomy for prophylaxis affects perioperative outcomes compared with resection performed for biopsy proven malignancy.The American College of Surgeons National Surgical Quality Improvement Program database was queried for subjects who underwent simple or subcutaneous mastectomy between 2007 and 2012. Patient demographic characteristics, comorbid conditions, and postoperative complications were analyzed.Of the 30,803 patients, 30,644 (99.5%) underwent therapeutic mastectomy and 159 (0.5%) underwent prophylactic mastectomy. Subjects who underwent prophylactic surgery were more likely to be younger (45 vs. 58 years; P .01) and white (134 [84%] vs. 20,647 [67%]; P .01). Surgery time was significantly greater in the prophylactic group (265 vs. 166 minutes; P .01). There was no significant difference in mortality between groups. There was a trend toward greater 30-day morbidity (15 [9%] vs. 1835 [6%]; P = .09) and occurrence of deep venous thrombosis (DVT; 2 [1%] vs. 74 [0.2%]; P = .06) in those who underwent prophylactic mastectomy. After age adjustment, the prophylactic group showed a nearly sixfold increase in DVT (odds ratio [OR], 5.77; 95% confidence interval [CI], 1.37-24.22), which persisted when controlling for surgery time (OR, 4.95; 95% CI, 1.18-20.86).Prophylactic simple or subcutaneous mastectomy incurs significant additional 30-day postoperative morbidity related to perioperative DVT. Risk-mitigating strategies should be considered in the perioperative care of this patient population.

Key Points Question Does postpartum blood pressure trajectory after a hypertensive disorder of pregnancy differ by race? Findings In this prospective cohort study that included 1077 women after a hypertensive disorder of pregnancy, blood pressure trajectories evaluated using mixed-effects linear regression models differed significantly by self-reported race. At the conclusion of the study, 68% of Black women and 51% of White women met the criteria for stage 1 or stage 2 hypertension. Meaning This study suggests that postpartum blood pressure trajectories indicate persistence of higher blood pressures among Black women in this cohort, which may have important implications for postpartum morbidity and mortality associated with hypertensive and cardiovascular conditions in this population., Importance Maternal morbidity and mortality are increasing in the United States, most of which occur post partum, with significant racial disparities, particularly associated with hypertensive disorders of pregnancy. Blood pressure trajectory after a hypertensive disorder of pregnancy has not been previously described. Objectives To describe the blood pressure trajectory in the first 6 weeks post partum after a hypertensive disorder of pregnancy and to evaluate whether blood pressure trajectories differ by self-reported race. Design, Setting, and Participants This prospective cohort study included deliveries between January 1, 2018, and December 31, 2019. Women with a clinical diagnosis of a hypertensive disorder of pregnancy were enrolled in a postpartum remote blood pressure monitoring program at the time of delivery and were followed up for 6 weeks. Statistical analysis was performed from April 6 to 17, 2020. Main Outcomes and Measures Mixed-effects regression models were used to display blood pressure trajectories in the first 6 weeks post partum. Results A total of 1077 women were included (mean [SD] age, 30.2 [5.6] years; 804 of 1017 White [79.1%] and 213 of 1017 Black [20.9%]). Systolic and diastolic blood pressures were found to decrease rapidly in the first 3 weeks post partum, with subsequent stabilization (at 6 days post partum: mean [SD] peak systolic blood pressure, 146 [13] mm Hg; mean [SD] peak diastolic blood pressure, 95 [10] mm Hg; and at 3 weeks post partum: mean [SD] peak systolic blood pressure, 130 [12] mm Hg; mean [SD] peak diastolic blood pressure, 85 [9] mm Hg). A significant difference was seen in blood pressure trajectory by race, with both systolic and diastolic blood pressure decreasing more slowly among Black women compared with White women (mean [SD] peak systolic blood pressure at 1 week post partum: White women, 143 [14] mm Hg vs Black women, 146 [13] mm Hg; P = .01; mean [SD] peak diastolic blood pressure at 1 week post partum: White women, 92 [9] mm Hg vs Black women, 94 [9] mm Hg; P = .02; and mean [SD] peak systolic blood pressure at 3 weeks post partum: White women, 129 [11] mm Hg vs Black women, 136 [15] mm Hg; P, This cohort study describes the blood pressure trajectory in the first 6 weeks post partum after a hypertensive disorder of pregnancy and evaluates whether blood pressure trajectories differ by self-reported race.

Objective The aim of study is to compare the performance of ultrasonographic customized and population fetal growth standards for prediction adverse perinatal outcomes. Study Design This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, in which l data were collected at visits throughout pregnancy and after delivery. Percentiles were assigned to estimated fetal weights (EFWs) measured at 22 to 29 weeks using the Hadlock population standard and a customized standard (www.gestation.net). Areas under the curve were compared for the prediction of composite and severe composite perinatal morbidity using EFW percentile. Results Among 8,701 eligible study participants, the population standard diagnosed more fetuses with fetal growth restriction (FGR) than the customized standard (5.5 vs. 3.5%, p The population standard diagnosed FGR among black women and Hispanic women at nearly double the rate it did among white women (p Conclusion At 22 to 29 weeks' gestation, EFW percentile alone poorly predicts perinatal morbidity whether using customized or population fetal growth standards. The population standard diagnoses FGR at increased rates in subgroups not at increased risk of morbidity and at lower rates in subgroups at increased risk of morbidity, whereas the customized standard does not.

Introduction The Liver X Receptors (LXRs) drive the transcriptional response to excess intracellular cholesterol. Oxysterols, the products of cholesterol oxidation, are activating ligands for LXR that can accumulate under conditions of oxidative stress and disrupt cholesterol homeostasis. While activation of LXR inhibits trophoblast differentiation, the impact of LXR on trophoblast physiology or cholesterol homeostasis is incompletely understood. We sought to determine if the effects of LXR activation can be ameliorated through modification of cholesterol bioavailability or inhibition of LXR-driven cholesterol efflux in trophoblasts. Methods We measured the effect of oxysterol exposure on BeWo cells and primary human trophoblasts (PHT cells) cultured in lipoprotein-deficient medium. We also measured the effect of the synthetic, LXR-specific ligand T0901317 on PHT cell differentiation and survival. Finally, we silenced the ATP-binding cassette transporter A1 (ABCA1), a transcriptional target of LXR that drives cholesterol efflux, to determine if inhibition of cholesterol efflux could block the effects of T0901317. Results Oxysterols inhibited BeWo survival and PHT cell differentiation, and these effects were blocked by cholesterol supplementation. T0901317 also inhibited PHT cell differentiation, and this effect was similarly blocked by cholesterol. Unlike cholesterol however, ABCA1 silencing did not modify the effect of T0901317 on PHT cell differentiation. Discussion Oxysterols and LXR inhibit trophoblast survival and differentiation exclusively in conditions of cholesterol scarcity. These findings underscore the importance of cholesterol homeostasis in the maintenance of placental function and suggest that pathways regulating cholesterol homeostasis may represent therapeutic targets to mitigate harmful sequelae of placental injury.

Introduction We have previously shown that miRNAs produced from the Chromosome 19 MiRNA Cluster (C19MC), which are expressed almost exclusively in primate trophoblasts and are released into the maternal circulation, reduce viral replication in non-placental cells and can modulate migratory behavior of extravillous trophoblast. We sought to define the expression pattern of C19MC miRNA in early pregnancy and in response to viral infection in vitro and in vivo . Methods We prospectively followed women undergoing in vitro fertilization (IVF) and determined their blood level of C19MC miRNA using RT-qPCR. To examine the effect of viral exposure on C19MC miRNAs expression, we used three systems: (1) a transgenic mouse overexpressing the C19MC cluster and exposed to Togaviridae during pregnancy, (2) cultured primary human trophoblasts exposed to Vesicular Stomatitis Virus in vitro , and (3) amniotic fluid from women exposed to cytomegalovirus during pregnancy. Results In 27 IVF pregnancies, C19MC miRNAs were detected as early as 2 weeks after implantation, and their levels increased thereafter. There was no change in C19MC miRNA expression levels in the mouse placenta in response to viral exposure. Similarly, Vesicular Stomatitis Virus infection of primary human trophoblast did not selectively increase C19MC miRNA expression. C19MC miRNA expression in the amniotic fluid was not affected by vertical transmission of cytomegalovirus. Discussion The expression of C19MC miRNAs in maternal circulation very early in pregnancy suggests a role in the establishment of the maternal-fetal interface. The levels of C19MC miRNA are not influenced by diverse types of viral infection.

The brain’s ability to associate different stimuli is vital to long-term memory, but how neural ensembles encode associative memories is unknown. Here we studied how cell ensembles in the basal and lateral amygdala (BLA) encode associations between conditioned and unconditioned stimuli (CS, US). Using a miniature fluorescence microscope, we tracked BLA ensemble neural Ca2+ dynamics during fear learning and extinction over six days in behaving mice. Fear conditioning induced both up- and down-regulation of individual cells’ CS-evoked responses. This bi-directional plasticity mainly occurred after conditioning and reshaped the CS ensemble neural representation to gain similarity to the US-representation. During extinction training with repetitive CS presentations, the CS-representation became more distinctive without reverting to its original form. Throughout, the strength of the ensemble-encoded CS-US association predicted each mouse’s level of behavioral conditioning. These findings support a supervised learning model in which activation of the US-representation guides the transformation of the CS-representation.

OBJECTIVE: To evaluate the feasibility, acceptability, and compliance of a remote blood pressure monitoring protocol implemented as a quality improvement measure at the hospital level for management of hypertension in postpartum women after hospital discharge. METHODS: This is an ongoing quality improvement project that included women admitted to the postpartum unit of a single tertiary care hospital. We designed nursing call center-driven blood pressure management and treatment algorithms which were initiated after hospital discharge until 6 weeks postpartum. Women are eligible to participate if they have a diagnosis of chronic hypertension, superimposed preeclampsia, gestational hypertension, preeclampsia, or postpartum hypertension and have access to a text messaging-enabled smartphone device. After identification by an obstetric care provider, women are enrolled into the program, which is automatically indicated in the electronic medical record. Maternal, obstetric, and sociodemographic data were obtained from the electronic medical record. RESULTS: Between February 2018 and January 2019, we enrolled 499 patients. Here we report on the first 409 enrolled patients. Participants include 168 (41%) with gestational hypertension, 179 (44%) with preeclampsia with no history of chronic hypertension, 49 (12%) with chronic hypertension with superimposed preeclampsia, and 13 (3%) with postpartum preeclampsia. One hundred seventy-one (42%) participants had antihypertensives initiated or titrated through the program. Three hundred forty women (83%) continued the program beyond 3 weeks postpartum, and 360 (88%) attended an in-person 6-week postpartum visit. Two hundred thirty-five out of 250 women who completed a postprogram survey (94%) reported satisfaction with the program. CONCLUSION: In this study, we detail results from an ongoing remote blood pressure monitoring program. We demonstrate high compliance, retention, and patient satisfaction with the program. This is a feasible, scalable remote monitoring program connected to the electronic medical record.

Background: Cicatricial alopecia is a type of permanent hair loss in which the hair follicle is replaced by scar tissue. Given its relatively low incidence, limited information is available regarding baseline hair characteristics, onset, and other disease-associated factors. Objective: We sought to further elucidate this information in our lichen planopilaris (LPP) patients. Methods: Between 1993 and 2016, 505 patients were diagnosed with biopsy-proven LPP. Of these patients, we mailed a 20-question survey to 420 patients with updated mailing address and contact information. Responses were received from 129 of 420 patients for a response rate of 30.7%. A total of 108 patients completed the survey and 21 patients declined participation. Descriptive analysis was performed using JMP software. Results: Median age at time of pathologic diagnosis was 58 years, with self-reported average age of onset accordingly from 50 to 60 years. Approximately 15% of patients were diagnosed with frontal fibrosing alopecia (FFA), a subtype of LPP. Median follow-up from date of pathologic diagnosis was 72 months. At baseline, 46 out of 108 patients (42.6%) endorsed having thicker hair than peers in childhood. No trend was identified in the rate of traction hairstyle use in childhood, current use of cosmetics, sunscreen, or facial cleanser. Conclusions: Within our LPP cohort, FFA subtype pathology comprised approximately 15% of cases. There was no trend toward sunscreen use and FFA subtype. Our findings support previously published studies in terms of average age at disease onset, location of hair loss, and median follow-up at 72 months (range: 29–273) from date of pathologic diagnosis. Keywords: Lichen planopilaris, Frontal fibrosing alopecia, Natural history, Survey, Sunscreen, Facial cosmetics

Background Antenatal detection of fetal growth restriction (FGR) prompts antepartum surveillance to reduce perinatal mortality, yet most cases of FGR are undetected. Objective This study aims to compare rates of adverse neonatal outcomes when FGR is detected versus undetected. Study Design Small-for-gestational-age (SGA) newborns (birth weight Results Out of 29,885 neonates, 2,475 (8.3%) were SGA. Out of the 826 (33%) SGA neonates who underwent growth ultrasound, 185 (22%) were considered FGR. In the SGA-no US group, the adjusted odds ratio (aOR) for Apgar Conclusion Fetal growth ultrasound effectively stratifies risk amongst SGA neonates.

SummaryFollowing skeletal muscle injury, muscle stem cells (satellite cells) are activated, proliferate, and differentiate to form myofibers. We show that mRNA-decay protein AUF1 regulates satellite cell function through targeted degradation of specific mRNAs containing 3′ AU-rich elements (AREs). auf1−/− mice undergo accelerated skeletal muscle wasting with age and impaired skeletal muscle repair following injury. Satellite cell mRNA analysis and regeneration studies demonstrate that auf1−/− satellite cell self-renewal is impaired due to increased stability and overexpression of ARE-mRNAs, including cell-autonomous overexpression of matrix metalloprotease MMP9. Secreted MMP9 degrades the skeletal muscle matrix, preventing satellite-cell-mediated regeneration and return to quiescence. Blocking MMP9 activity in auf1−/− mice restores skeletal muscle repair and maintenance of the satellite cell population. Control of ARE-mRNA decay by AUF1 represents a mechanism for adult stem cell regulation and is implicated in human skeletal muscle wasting diseases.

Acquired progressive lymphangioma (benign lymphangioendothelioma) is a rare lymphatic anomaly of unclear pathogenesis. Excision is generally advised for local disease, although other therapies have been tried. This report describes a unique case of extensive acquired progressive lymphangioma involving the abdomen, genitalia, and lower extremity of a 1-year-old boy. Rapid progression and multisite involvement required exploration of nonsurgical options for management.

Objective To characterize the clinicopathologic findings, comorbidities, and treatment outcomes of women with frontal fibrosing alopecia. Patients and Methods Retrospective review of women with frontal fibrosing alopecia at Mayo Clinic from January 1, 1992, to February 22, 2016. The terms "scarring alopecia," "lichen," "planopilaris," "fibrosing," and "alopecia" were used for the search of female patients aged 1 to 100 years. A total of 686 patients were reviewed to confirm the diagnosis of frontal fibrosing alopecia. Patients were included if they met diagnostic criteria. Results A total of 148 women with frontal fibrosing alopecia were identified, with a mean age of 62 years; 60.1% presented with eyebrow loss; 67.6% and 27.7% described preceding or concurrent pruritus and trichodynia, respectively; 44.6% had a history of hypothyroidism; 13% had a history of surgical menopause; and 63.3% had a history of hormone replacement therapy. A total of 18.2% had lichen planus at other body sites, and 26.3% achieved disease stabilization, often requiring combination therapies. The mean time to remission was 1.8 years. Conclusion Patients with frontal fibrosing alopecia typically present with frontotemporal and eyebrow alopecia with preceding symptoms. Hypothyroidism and a history of hysterectomy may be more common than previously reported. Time to presentation, diagnosis, and stabilization is often months to years. Patients who lack treatment response may present with eyebrow loss, eyelash loss, and facial papules. Combination therapy is helpful in achieving slowing of disease progression or disease stabilization, although recurrence is common. Additional studies on treatment and efficacy are needed. Limitations to this study include the retrospective design and varied follow-up.

We attempted to determine the feasibility of studying prehabilitation exercises to improve shoulder pain and abduction range of motion (ROM) after breast cancer surgery. We evaluated methods of exercise teaching and assessed effect on postsurgical seroma formation. This was a feasibility study with two non-blinded groups of subjects randomized by timing of appointment. This single-site study was performed at an academic tertiary medical center. Sixty cancer patients were randomly assigned to either group 1, in-person teaching arm, n = 36, or group 2, video-only teaching arm, n = 24. Forty-five patients completed the study. Shoulder exercises were assigned to both groups 1 month prior to surgery during evaluation. Group 1 received in-person instruction on exercises, plus an information sheet with exercises and a link to an online video. Group 2 received only the information sheet with exercises and a link to the online video. The primary outcomes considered are as follows: exercise compliance, shoulder pain (via visual analog scale), shoulder abduction ROM (via goniometer), and presence or absence of seroma. Seventy-six percent of study patients chose to exercise. There was no difference in exercise compliance between in-person teaching versus video teaching (75 %, 24/32 vs. 77 %, 10/13, OR = 1.03). Sixty-six of patients (20/30) lost greater than 10° shoulder abduction ROM at 1 month post surgery. Twenty-nine of patients (9/31) had worse shoulder pain than baseline at 1 month post surgery (24 %, 6/25 exercisers, and 50 %, 3/6 non-exercisers). Fifteen percent of patients (4/27) had worse shoulder pain than baseline at 3 months post surgery (8 %, 2/23 exercisers, and 100 %, 2/2 non-exercisers). Prehabilitation exercise program inferred no additional risk of seroma formation (Exercisers 21 %, 7/33 vs. non-exercisers 22 %, 2/9, OR = 0.94). Our subjects were able to perform three exercises independently in the preoperative period. A high-quality randomized controlled trial is necessary to assess the appropriate timing and efficacy of this intervention.

Objective This study aims to determine the risk of adverse outcomes associated with the current diagnostic criteria for fetal macrosomia. Study Design We evaluated three techniques for characterizing birth weight as a predictor of shoulder dystocia or third- or fourth-degree laceration in 79,879 vaginal deliveries. First, we compared deliveries with birth weights above or below 4,500 g. We then performed logistic regression using birth weight as a continuous predictor, both with and without fractional polynomial transformation. Finally, we calculated the number of cesarean sections required to prevent one incident of the interrogated outcomes (number needed to treat [NNT]). Results Rates of adverse intrapartum outcomes increase incrementally with increasing birth weight and are predicted most accurately with logistic regression following fractional polynomial transformation. The NNT for third- or fourth-degree laceration dropped from 14.3 (95% confidence interval [CI], 13.9–14.7) at a birth weight of 3,500 g to 6.4 (95% CI, 6.1–6.8) at 4,500 g and, for shoulder dystocia, from 54.9 (95% CI, 51.5–58.6) at 3,500 g to 5.6 (95% CI, 5.2–6.0) at 4,500 g. Conclusion The conventional distinction between “normal” and “macrosomic” does not reflect the incremental effect of increasing birth weight on the risk of obstetric morbidity. Outcomes analysis can inform fetal growth standards to better reflect relevant thresholds of risk.

While ongoing experience proceeds continuously, memories of past experience are often recalled as episodes with defined beginnings and ends. The neural mechanisms that lead to the formation of discrete episodes from the stream of neural activity patterns representing ongoing experience are unknown. To investigate these mechanisms, we recorded neural activity in the rat hippocampus and prefrontal cortex, structures critical for memory processes. We show that during spatial navigation, hippocampal CA1 place cells maintain a continuous spatial representation across different states of motion (movement and immobility). In contrast, during sharp-wave ripples (SWRs), when representations of experience are transiently reactivated from memory, movement- and immobility-associated activity patterns are most often reactivated separately. Concurrently, distinct hippocampal reactivations of movement- or immobility-associated representations are accompanied by distinct modulation patterns in prefrontal cortex. These findings demonstrate a continuous representation of ongoing experience can be separated into independently reactivated memory representations.

Rosai-Dorfman disease (also known as sinus histiocytosis with massive lymphadenopathy) is a rare benign proliferative disorder of histiocytes that typically involves the lymph nodes and can also involve extranodal sites. Rosai-Dorfman disease confined to the breast is extremely rare, but important to recognize as it can mimic malignancy. We present the case of a 63-year-old woman who presented with a palpable breast lump that was highly suspicious for malignancy based on mammogram and ultrasound appearance. Biopsy revealed inflammatory tissue with lymphoplasmacytic and histiocytic predominance. The diagnosis of Rosai-Dorfman was made based on characteristic staining of histiocytes with S-100 and the presence of emperipolesis. Early recognition of this benign disease entity spared the patient further investigation and surgical intervention.

Intrauterine mammalian development depends on the preservation of placental function. The expression of the protein N-myc downstream–regulated gene 1 (NDRG1) is increased in placentas of human pregnancies affected by fetal growth restriction and in hypoxic primary human trophoblasts, where NDRG1 attenuates cell injury. We sought to assess the function of placental NDRG1 in vivo and tested the hypothesis that NDRG1 deficiency in the mouse embryo impairs placental function and consequently intrauterine growth. We found that Ndrg1 knock-out embryos were growth restricted in comparison to wild-type or heterozygous counterparts. Furthermore, hypoxia reduced the survival of female, but not male, knock-out embryos. Ndrg1 deletion caused significant alterations in placental gene expression, with a marked reduction in transcription of several lipoproteins in the placental labyrinth. These transcriptional changes were associated with reduced fetal:maternal serum cholesterol ratio exclusively in hypoxic female embryos. Collectively, our findings indicate that NDRG1 promotes fetal growth and regulates the metabolic response to intrauterine hypoxic injury in a sexually dichotomous manner.

Activation of the inflammasome is implicated in the pathogenesis of an increasing number of inflammatory diseases, including Alzheimer's disease (AD). Research reporting inflammatory changes in post mortem brain tissue of individuals with AD and GWAS data have convincingly demonstrated that neuroinflammation is likely to be a key driver of the disease. This, together with the evidence that genetic variants in the NLRP3 gene impact on the risk of developing late-onset AD, indicates that targetting inflammation offers a therapeutic opportunity. Here, we examined the effect of the small molecule inhibitor of the NLRP3 inflammasome, MCC950, on microglia in vitro and in vivo. The findings indicate that MCC950 inhibited LPS+Aβ-induced caspase 1 activation in microglia and this was accompanied by IL-1β release, without inducing pyroptosis. We demonstrate that MCC950 also inhibited inflammasome activation and microglial activation in the APP/PS1 mouse model of AD. Furthermore, MCC950 stimulated Aβ phagocytosis in vitro, and it reduced Aβ accumulation in APP/PS1 mice, which was associated with improved cognitive function. These data suggest that activation of the inflammasome contributes to amyloid accumulation and to the deterioration of neuronal function in APP/PS1 mice and demonstrate that blocking assembly of the inflammasome may prove to be a valuable strategy for attenuating changes that negatively impact on neuronal function.

Preterm birth has staggering health implications, and yet the causes of most cases are still unknown. Placental features have been understudied as an etiology for preterm birth, and the association between placental pathologic lesions and neonatal outcomes are incompletely understood.We sought to characterize births according to placental pathology and relate these to adverse neonatal outcomes.We studied 20,091 births (15,710 term and 4381 preterm) with placental evaluations. Births were classified according to the presence or absence of placental lesions consistent with malperfusion (vasculopathy, infarct, advanced villous maturation, perivillous fibrin, fibrin deposition) and intrauterine inflammation/infection (chorioamnionitis, funisitis, vasculitis). Outcomes were gestational week of delivery, birthweight z-score, neonatal respiratory distress syndrome, and intraventricular hemorrhage.Among all preterm births, evidence of placental malperfusion was identified more often than inflammation/infection (50.6% vs 27.3%, P .0001). Placental malperfusion was associated with reduced fetal growth (adjusted birthweight z-score, -0.83, P.0001) and lesions of inflammation/infection were associated with earlier delivery (adjusted difference -2.08 weeks, P.0001) than those with no lesions. When both placental lesions were present, earlier delivery (adjusted difference -2.28 weeks, P.0001) and reduced fetal growth (adjusted birthweight z-score difference, -0.24, P = .001) were observed more often than when neither lesion was present. Findings were similar when restricted to cases of spontaneous preterm birth. Intraventricular hemorrhage was higher in preterm births with malperfusion lesions than cases with no lesions (7.6% vs 3.4%; odds ratio, 1.98; confidence interval, 1.18-3.32), accounting for gestational age and other covariates.Placental pathology provides important insight into subtypes of preterm birth with adverse neonatal outcomes. Co-occurrence of malperfusion and inflammation/infection, especially among spontaneous preterm births, may be a novel pattern of placental injury linked to severe adverse outcomes.

Objective We assessed the effect of an open vascular simulation course on the surgical skill of junior surgical residents in performing a vascular end-to-side anastomosis and determined the course length required for effectiveness. We hypothesized that a 6-week course would significantly increase the surgical skill of junior residents in performing an end-to-side anastomosis, while a 3-week course would not. Methods We randomized 37 junior residents (postgraduate year 1 to 3) to a course consisting of three (short course, n=18) or six (long course, n=19) consecutive weekly 1-hour teaching sessions. Content focused on instrument recognition and performance of an end-to-side vascular anastomosis using a simulation model. A standardized 50-point vascular skills assessment (SVSA) measured knowledge and technical proficiency. Senior residents (postgraduate year 4 to 5) were tested at baseline. Junior residents were tested at baseline and at 1 and 16 weeks after course completion, and their scores were compared with baseline and senior resident scores. Residents and faculty completed a standardized anonymous evaluation of the course. Results Baseline scores between short-course and long-course participants were not different. At baseline, junior residents had significantly lower SVSA scores than senior residents (36 ± 7 vs 41.4 ± 2.5; P = .002). One week after course completion, SVSA scores for short-course (43.5 ± 2.9 vs 34.2 ± 7.5; P = .008) and long-course (43.9 ± 5.6 vs 38.3 ± 5.9; P = .006) participants were significantly improved from baseline. SVSA scores decreased slightly at 16 weeks but remained above baseline in short-course (39 ± 6.2 vs 34.2 ± 7.5; P = .03) and long-course (40 ± 4.5 vs 38.3 ± 5.9; P = .08) participants. Long vs short course length didnot affect improvement in SVSA scores at 1 or 16 weeks. In short-course and long-course participants, SVSA scores at 1 and 16 weeks were not significantly different from senior resident scores. Course ratings were high, and 95% of residents indicated the course "made them a better surgeon." Residents and faculty felt the educational benefit of the course merited the investment of resources. Conclusions An open vascular simulation course consisting of three weekly 1-hour sessions increased the surgical skill of junior residents in performing a vascular end-to-side anastomosis to that of senior residents on a standardized assessment. A 6-week course provided no additional benefit. This study supports the use of an open vascular simulation course to teach vascular surgical skills to junior residents. A course consisting of three 1-hour sessions is an effective and efficient component of a simulation program for junior surgical residents in a busy surgical center.

ObjectivesWe sought to determine the level of procedural justice experienced by individuals at the time of involuntary admission and whether this influenced future engagement with the mental health services.MethodsOver a 15-month period, individuals admitted involuntarily were interviewed prior to discharge and at one-year follow-up.ResultsEighty-one people participated in the study and 81% were interviewed at one-year follow-up. At the time of involuntary admission, over half of individuals experienced at least one form of physical coercion and it was found that the level of procedural justice experienced was unrelated to the use of physical coercive measures. A total of 20% of participants intended not to voluntarily engage with the mental health services upon discharge and they were more likely to have experienced lower levels of procedural justice at the time of admission. At one year following discharge, 65% of participants were adherent with outpatient appointments and 18% had been readmitted involuntarily. Insight was associated with future engagement with the mental health services; however, the level of procedural justice experienced at admission did not influence engagement.ConclusionsThis study demonstrates that the use of physical coercive measures is a separate entity from procedural justice and perceived pressures.

Bioencapsulation of living cells into silica materials derived from the sol–gel process has resulted in novel hybrid living materials with exciting functionalities. Despite the many successes in this field, long-term viability and activity of the encapsulated cells remain a significant obstacle to producing practical and robust devices, e.g., whole-cell-based biosensors. We report the first study on the effects of various media additives and the metabolic phase of encapsulated cells on long-term viability and the rate of inducible gene expression. Saccharomyces cerevisiae (S. cerevisiae) cells, genetically engineered to produce yellow fluorescent protein (YFP) in response to galactose, were encapsulated in poly(glycerol) silicate derived matrices. Surprisingly, we find that addition of media components to the glycerol-silica matrix adversely impacted long-term viability in all cases studied, with a 1.3, 1.4, or 5.4 fold decrease in viability after only 9 days of storage in matrices containing yeast pepton...

Adrenalectomy remains the definitive therapy for most adrenal neoplasms. Introduced in the 1990s, laparoscopic adrenalectomy is reported to have lower associated morbidity and mortality. This study aimed to evaluate national adrenalectomy trends, including major postoperative complications and perioperative mortality. The Nationwide Inpatient Sample was queried to identify all adrenalectomies performed during 1998–2006. Univariate and multivariate logistic regression were performed, with adjustments for patient age, sex, comorbidities, indication, year of surgery, laparoscopy, hospital teaching status, and hospital volume. Annual incidence, major in-hospital postoperative complications, and in-hospital mortality were evaluated. Using weighted national estimate, 40,363 patients with a mean age of 54 years were identified. Men made up 40% of these patients, and 77% of the patients were white. The majority of adrenalectomies (83%) were performed for benign disease. The annual volume of adrenalectomies increased from 3,241 in 1998 to 5,323 in 2006 (p

Unconventional gas drilling (UGD) has enabled extraordinarily rapid growth in the extraction of natural gas. Despite frequently expressed public concern, human health studies have not kept pace. We investigated the association of proximity to UGD in the Marcellus Shale formation and perinatal outcomes in a retrospective cohort study of 15,451 live births in Southwest Pennsylvania from 2007–2010. Mothers were categorized into exposure quartiles based on inverse distance weighted (IDW) well count; least exposed mothers (first quartile) had an IDW well count less than 0.87 wells per mile, while the most exposed (fourth quartile) had 6.00 wells or greater per mile. Multivariate linear (birth weight) or logistical (small for gestational age (SGA) and prematurity) regression analyses, accounting for differences in maternal and child risk factors, were performed. There was no significant association of proximity and density of UGD with prematurity. Comparison of the most to least exposed, however, revealed lower birth weight (3323 ± 558 vs 3344 ± 544 g) and a higher incidence of SGA (6.5 vs 4.8%, respectively; odds ratio: 1.34; 95% confidence interval: 1.10–1.63). While the clinical significance of the differences in birth weight among the exposure groups is unclear, the present findings further emphasize the need for larger studies, in regio-specific fashion, with more precise characterization of exposure over an extended period of time to evaluate the potential public health significance of UGD.

ResumenEl propósito de este estudio era identificar los rasgos de la esquizofrenia de primer episodio que predicen el cumplimiento de la medicación antipsicótica en el seguimiento a los 6 meses. Utilizamos instrumentos validados para evaluar las variables clínicas y sociodemográficas en todos los pacientes con esquizofrenia de primer episodio de un área geográfica definida ingresados en un hospital psiquiátrico de Dublín durante un periodo de cuatro años (n = 100). En el seguimiento a los 6 meses (n = 60) evaluamos el cumplimiento de la medicación utilizando la Entrevista de Cumplimiento. Un tercio de los pacientes con esquizofrenia no tomaba la medicación a los seis meses de su primer episodio de enfermedad. Los niveles elevados de síntomas positivos en la linea de base, la falta de conciencia de la enfermedad en la línea de base, el uso inadecuado de alcohol en la línea de base y el uso inadecuado anterior de drogas predicen el incumplimiento. Estos resultados indican que un subgrupo identificable de pacientes con esquizofrenia de primer episodio tiene un riesgo alto de incumplimiento temprano de la medicación. Aunque las puntuaciones altas de síntomas positivos preceden y predicen el incumplimiento en la mayoría de los pacientes, la reducción de la conciencia de la enfermedad es el mejor predictor del incumplimiento en los pacientes que no utilizan inadecuadamente el alcohol u otras drogas.

ResumenLa esquizofrenia se asocia con desarrolló neural alterado. Evaluamos los signos neurológicos menores (SNM) y las anomalías dermatoglíficas (recuento total de crestas a-b [RTCAB] y recuento total crestas digitales [RTCD]) en 15 pares de gemelos concordantes y dis-cordantes para esquizofrenia. Las diferencias intrapar en las puntuaciones tanto de SNL como de RTCAB fueron significativamente mayo-res en los pares discordantes comparado con los pares monocigóticos concordantes. No hubo diferencias significativas en las puntuaciones de SNM y RTCAB entre los sujetos con esquizofrenia y los co-gemelos sin la enfermedad. Sin embargo, los gemelos discordantes monocigóticos con esquizofrenia tenían recuentos de crestas a-b (RCAB) mayores en su mano derecha comparado con sus co-gemelos sin la enfermedad. Estos hallazgos indican que un acontecimiento ambiental no identificado que actúa entre las semanas 6 y 15 de la gestación afecta al desarrollo de los gemelos monocigóticos que continúan hasta desarrollar esquizofrenia, pero no tiene un efecto correspondiente en sus co-gemelos que no desarrollan la enfermedad. El efecto de este acontecimiento sobre los perfiles dermatoglíficos parece laterali-zado a la mano derecha en los gemelos afectados.

BACKGROUND: Patients with heparin-induced thrombocytopenia and thrombosis may be acutely anticoagulated with direct thrombin inhibitors (DTIs). The anticoagulation is typically monitored using the activated partial thromboplastin time (aPTT) or ecarin clotting time (ECT). OBJECTIVE: To compare 14 methods for measuring aPTT, as well as ECT and thrombin inhibitor management test (TIM), in samples containing DTIs. METHODS: DTIs were added to pooled normal plasma to achieve low (0.1–1.2 μg/mL) and high (1.5–8.0 μg/mL) drug concentrations. Each low-concentration DTI sample was tested using all aPTT reagents, while each low- and high-concentration DTI was tested using the ECT and TIM. RESULTS: All aPTT reagents had a significant dose-dependent correlation with drug concentration. Only Actin FSL and APTT-S demonstrated equivalent aPTT ratios obtained from any DTI. The TAS-aPTT was the most sensitive aPTT reagent to argatroban, with the aPTT ranging from 52.7 to 121.2 seconds corresponding to 0.1 to 1.2 μg/mL of drug concentration. The TAS-aPTT and Pathromtin were the most sensitive aPTT reagents to bivalirudin, with aPTTs of 87.4 seconds and 101.5 seconds, respectively, at 1.2 μg/mL of drug. Pathromtin was the most sensitive aPTT reagent to lepirudin, with a maximum aPTT of 108.9 seconds at 1.2 μg/mL of drug. There was no statistically significant difference between the TIM and ECT clotting times for each DTI. Lepirudin and bivalirudin ECT and TIM clotting times were equivalent. CONCLUSIONS: There are unique differences between reagent manufacturers in the monitoring of DTIs. Acceptable alternatives to aPTT monitoring of DTI anticoagulation include the ECT and TIM.

An increase in the prevalence of Salmonella enterica serotype Typhimurium DT104 has been reported worldwide. This study examined the prevalence of this microorganism in poultry environmental samples from commercial layer flocks and pullet environments as well as the sensitivity and specificity of a PCR-based method, and multiple antibiotic resistance profile of Salmonella serogroup B isolates in relation to the serotype and phagetype reference method for the identification of Salmonella Typhimurium DT104. A total of 435 Salmonella isolates were obtained from poultry house environmental samples tested during a 20-month period representing a prevalence of 5.5%. Of these, 313 (72%) isolates were identified as Salmonella serogroup B isolates. These isolates were tested by a PCR-based assay, and for resistance to five antibiotics: ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline (ACSSuT) for the rapid identification of Salmonella Typhimurium DT104. Upon comparing the antibiotic resistance and PCR results with serotype and phage type data, the sensitivity and specificity for the identification of Salmonella Typhimurium DT104 of both methods were found to be 100%, and 99.6%, respectively. Both methods can be completed within 24 h after obtaining an isolate, while serotyping and phagetyping required more than 5 days to complete.

ResumenTener un diagnóstico de esquizofrenia es un factor de riesgo para el ingreso no voluntario en la asistencia hospitalaria psiquiátrica, pero tenemos una comprensión limitada de por qué algunos pacientes precisan un ingreso no voluntario y otros no. Intentamos identificar los predictores del ingreso no voluntario en el primer episodio de esquizofrenia. Utilizamos instrumentos validados para evaluar las variables clínicas y sociodemográficas en todos los pacientes (n = 78) con primer episodio de esquizofrenia de un área geográfica definida ingresados en un hospital psiquiátrico de Dublín durante un periodo de 4 años. No se pudo distinguir a los pacientes no voluntarios (n = 17) de los voluntarios (n = 61) de acuerdo con la edad, el género, la situación de convivencia, el estado civil, el abuso de drogas o la duración de la psicosis no tratada. Ni los síntomas positivos ni los negativos fueron predictores útiles del tipo de ingreso. La falta de insight fue un fuerte predictor del ingreso de tipo no voluntario.

We evaluated six D-dimer methods to determine their sensitivity, specificity, and negative predictive values (NPV) in symptomatic patients suspected of deep vein thrombosis (DVT). In patients suspected of DVT a whole blood D-dimer test (SimpliRED, Agen) was performed, and then tested using enzyme-linked immunosorbent assay (VIDAS D-Dimer, BioMerieux; Asserachrome D-Di, Stago International; Dimertest Gold, Agen) and automated immunoturbidometric methods (Advanced D-Dimer, Dade Behring; MiniQuant, Biopool). Each D-dimer method was independently compared with radiographic results to determine sensitivity and NPV. There were 151 patients enrolled in the study. Thirty-five (23.2%) patients had a positive Doppler ultrasound, with 26 proximal, eight distal, and one patient with both proximal and distal thrombus. Two patients (1.3%) had inconclusive studies and were excluded from the analyses. For all patients, the sensitivities for the rapid D-dimer methods were: SimpliRED, 82.3% [95% confidence interval (CI), 80.3-84.3%]; VIDAS D-Dimer, 91.4% (95% CI, 89.9-92.9%); MiniQuant D-Dimer, 96.3% (95% CI, 95.1-97.5%); and Advanced D-Dimer, 97.1% (95% CI, 96.3-97.9%). The sensitivity improved for SimpliRED (86.4%; 95% CI, 83.3-89.4%), VIDAS D-Dimer (95.5%; 95% CI, 85.0-100%), MiniQuant D-Dimer (100%; 95% CI, 96.9-100%) and Advanced D-Dimer (100%; 95% CI, 98.9-100%) in the inpatient population. The automated immunoturbidometric methods, the MiniQuant D-Dimer and Advanced D-Dimer, demonstrated comparable sensitivities and NPV with the VIDAS D-Dimer method in symptomatic patients suspected of DVT, which would suggest that these newer D-dimer methods could be used as part of the diagnostic algorithm for patients suspected of DVT.

Summary We used DNA macroarray analysis to identify genes that respond to the status of the intracellular acetyl phosphate (acP) pool. Genes whose expression correlated negatively with the ability to synthesize acP (i.e. negatively regulated genes) function primarily in flagella biosynthesis, a result consistent with observations that we published previously (Prus and Wolfe, 1994, Mol Microbiol 12: 973‐984). In contrast, genes whose expression correlated positively with the ability to synthesize acP (i.e. positively regulated genes) include those for type 1 pilus assembly, colanic acid (capsule) biosynthesis and certain stress effectors. To our knowledge, this constitutes the first report that these genes may respond to the status of the intracellular acP pool. Previously, other researchers have implicated flagella, type 1 pili, capsule and diverse stress effectors in the formation of biofilms. We therefore tested whether cells altered in their ability to metabolize acP could construct normal biofilms, and found that they could not. Cells defective for the production of acP and cells defective for the degradation of acP could both form biofilms, but these biofilms exhibited characteristics substantially different from each other and from biofilms formed by their wild-type parent. We confirmed the role of individual cell surface structures, the expression of which appears to correlate with acP levels, in fim or fli mutants that cannot assemble type 1 pili or flagella respectively. Thus, the information gained by expression profiling of cells with altered acP metabolism indicates that acP may help to co-ordinate the expression of surface structures and cellular processes involved in the initial stages of wild-type biofilm development.

The conjunctival microcirculation of 18 homozygous sickle cell disease (SCD) patients during steady-state, painful crisis, and postcrisis conditions was recorded on high-resolution videotapes using intravital microscopy. Selected videotape sequences were subsequently coded, frame-captured, studied, and blindly analyzed using computer-assisted image analysis protocols. At steady-state (baseline), all SCD patients exhibited some of the following morphometric abnormalities: abnormal vessel diameter, comma signs, blood sludging, boxcar blood flow phenomenon, distended vessels, damaged vessels, hemosiderin deposits, vessel tortuosity, and microaneurysms. There was a decrease in vascularity (diminished presence of conjunctival vessels) in SCD patients compared with non-SCD controls, giving the bulbar conjunctiva a “blanched” avascular appearance in most but not all SCD patients during steady-state. Averaged steady-state red cell velocity in SCD patients was slower than in non-SCD controls. During painful crisis, a further decrease in vascularity (caused by flow stoppage in small vessels) and a 36.7% ± 5.2% decrease in large vessel (mostly venular) diameter resulted. In addition, the conjunctival red cell velocities either slowed significantly (6.6% ± 13.1%; P

Human disease caused by enterohemorrhagic E. coli O157:H7 and other serotypes (EHEC) has been associated with bovine fecal contamination of food and the environment. The range of serotypes, low infectious dose, and numerous transmission vehicles for EHEC render development of detection methods for this pathogen complex. In this study, the hemolysin gene (EHEC- hly A) was targeted with oligonucleotides, and probe-target hybrids were amplified using strand displacement amplification (SDA). Amplicons were resolved in the complete reaction mix through changes in the fluorescence polarization (FP) of a fluorescein-labeled detector probe hybridized to the amplicons during amplification. Results combining EHEC- hly A, SDA, and FP were obtained within 35 min of reaction initiation. The test specificity was determined on EHEC strains representing 13 serotypes (49 isolates); and control uropathogenic, commensal, and other organisms (10 isolates). Statistical analysis of results indicated a sensitivity in the reaction vessel to 4.3 bacteria (95% confidence interval), and a specificity for EHEC (n=59) at 100% (P=5.11E-17; i.e. P<

The Liver X Receptors (LXRs) are critical transcriptional regulators of cellular metabolism that promote cholesterol efflux and lipogenesis in response to excess intracellular cholesterol. In contrast, the Sterol Response Element Binding Protein-2 (SREBP2) promotes the synthesis and uptake of cholesterol. Oxysterols are products of cholesterol oxidation that accumulate in conditions associated with increased cellular levels of reactive oxygen species, such as hypoxia and oxidative stress, activating LXR and inhibiting SREBP2. While hypoxia and oxidative stress are commonly implicated in placental injury, the impact of the transcriptional regulation of cholesterol homeostasis on placental function is not well characterized.We measured the effects of the synthetic LXR ligand T0901317 and the endogenous oxysterol 25-hydroxycholesterol (25OHC) on differentiation, cytotoxicity, progesterone synthesis, lipid droplet formation, and gene expression in primary human trophoblasts.Exposure to T0901317 promoted lipid droplet formation and inhibited differentiation, while 25OHC induced trophoblast toxicity, promoted hCG and progesterone release at lower concentrations with inhibition at higher concentrations, and had no effect on lipid droplet formation. The discrepant effect of these ligands was associated with distinct changes in expression of LXR and SREBP2 target genes, with upregulation of ABCA1 following 25OHC and T090317 exposure, exclusive activation of the lipogenic LXR targets SREBP1c, ACC1 and FAS by T0901317, and exclusive inhibition of the SREBP2 targets LDLR and HMGCR by 25OHC.These findings implicate cholesterol oxidation as a determinant of trophoblast function and activity, and suggest that placental gene targets and functional pathways are selectively regulated by specific LXR ligands.

Hypothesis: Children who undergo cardiopulmonary bypass (CPB) are proportionally more hemodiluted than adults who undergo CPB. Current methods of monitoring high-dose heparin sulfate anticoagulation are dependent on fibrinogen level. Because of the decreased fibrinogen levels in children, current methods of monitoring heparin anticoagulation overestimate their level of anticoagulation. Design: Prospective controlled trial. Main Outcome Measure: Production of thrombin (adequacy of anticoagulation). Methods: Children and adults undergoing cardiac surgery who received CPB were anticoagulated in the standard fashion as directed by activated clotting time (ACT) results. Each subject had blood sampled at baseline; heparinization; start of the CPB; CPB at 30, 60, and 90 minutes; and at termination of CPB. Samples were used to assess anticoagulation with the Heparin Management Test (less dependent on fibrinogen level than ACT). We also assessed 2 subclinical markers of thrombosis, thrombin-antithrombin complexes and prothrombin fragment F1.2; a marker of procoagulant reserve, fibrinogen; the natural antithrombotic, anti-thrombin; and heparin concentration. Results: Ten children and 10 adults completed the study. Children had lower fibrinogen levels than adults throughout CPB (P

A CD8+ T-cell leukemia was diagnosed in an aged female rhesus macaque. Although leukemia and lymphoma in nonhuman primates are commonly associated with simian T-lymphotropic virus, gibbon ape leukemia virus, oncogenic herpesviruses, and types C, D, and E retroviruses, this monkey was not infected with any of these viruses. However, the monkey did have antibodies against herpesvirus saimiri. This likely represents cross-reactivity of the herpesvirus saimiri assay with rhesus monkey rhadinovirus (RRV) antibodies; RRV was first described in rhesus macaques that were identified as having antibodies against herpesvirus saimiri. Rhesus rhadinovirus is a gamma herpesvirus, related antigenically to herpesvirus saimiri and Kaposi's sarcoma-associated herpesvirus (KSHV), which have been linked to lymphoproliferative disorders in primates and humans, respectively. Moreover, an oncogene has been recently identified in the RRV genome that is equivalent in position to the herpesvirus saimiri and KSHV oncogenes. Presently, the association of RRV infection with disease in nonhuman primates is unknown.

Background The whole blood D-dimer assay has gained recognition as a noninvasive test to rule out pulmonary embolism (PE) in medical patients. Methods We performed a whole blood D-dimer assay in medical and surgical patients undergoing either pulmonary angiogram or pulmonary ventilation perfusion scan for suspected PE or duplex Doppler or venogram for suspected deep venous thrombosis (DVT). Results A total of 483 patients were enrolled; 16 were excluded because of an equivocal pulmonary ventilation perfusion scan. The 467 remaining patients had a mean age of 56 +/- 27 years. There were 258 women and 209 men. A total of 353 patients were admitted to a medical service and 114 to surgery/ trauma. A total of 82 patients (18%) developed thromboembolism: 20 had PE, and 62 had DVT. Conclusion No surgical patient with PE or DVT (n = 27) had a negative D-dimer. A negative D-dimer result in a stable surgical patient should be considered conclusive evidence to rule out thromboembolism and, thus, negate the need for further diagnostic studies. In our surgical patients suspected of DVT or PE, had D-dimer been used, one third of the patients would have avoided an expensive or invasive diagnostic test.

ResumenObjetivo:Los informes subjetivos de respuestas disfóricas a la medicación neuroléptica son comunes en la práctica clínica. Sin embargo, los efectos secundarios cognitivos y afectivos de las medicaciones neurolépticas son difíciles de diferenciar de los síntomas de esquizofrenia. Tratamos de dilucidar la contribución relativa de los efectos secundarios extrapiramidales y los síntomas a la respuesta disfórica.Método:Se evaluó a 50 pacientes ambulatorios estables clínicamente con esquizofrenia que asistían a un centro de rehabilitación en cuanto a los efectos secundarios extrapiramidales y los síntomas antes de completar el inventario de actitud hacia los medicamentos (DAI).Resultados:La presencia de efectos secundarios extrapiramidales, encontrados en 28 pacientes (Z = -1,99, p = 0,05), y la gravedad de los síntomas negativos (r = -0,47, p = 0,001) se asociaban independientemente con la respuesta disfórica, explicando una proporción significativa de la varianza (R = 0,53, R2 = 25,2%, F = 9,27, gl = 2, p = 0,0004).Conclusiones:Los pacientes que comunican una respuesta disfórica que ellos asocian con las medicaciones neurolépticas tienen más efectos secundarios extrapiramidales y síntomas negativos más graves. Aunque estas respuestas pueden ser parte de los síntomas negativos de la enfermedad o deberse a otros factores como la depresión, planteamos la posibilidad de que puedan ser clínicamente indistinguibles del llamado "síndrome de déficit inducido por neurolépticos" y una medida subjetiva de él.