Search

Background: Pediatric Surgical Critical Care (PSCC) is a unique specialty incorporating fundamental principles of surgical, neonatal, and pediatric critical care. This study aims to characterize the current landscape of PSCC training to identify opportunities for educational standardization and improvement., Methods: An anonymous electronic survey-based assessment was distributed to the program directors (PDs) of all current ACGME-accredited PSCC fellowships (n = 14). The survey investigated two main program domains: administrative (program size, accreditation, recruitment strategies) and educational (curricula components, learning resources, rotation schedule). Graduate outcomes (estimated board passage rates) were also assessed. Descriptive statistics were performed., Results: The survey response rate was 100 %. The majority of primary administrative ACGME accreditation responsibilities are managed either by the pediatric surgery section/department (79 %) or the adult surgery department (21 %). Only 29 % of PDs use a pediatric specific structured curriculum that details specific benchmarks for medical and procedural knowledge. Formalized reading lists and standardized resources are utilized by 64 %. All programs offer recurrent educational lectures to fellows by a variety of faculty. There is marked heterogeneity related to time spent in various core and elective rotations. Average duration spent on a PSCC service was 5.1 months (0-10months). However, only 14 % of programs reported these months to consist of primary patient management responsibilities., Conclusion: This evaluation of PSCC fellowships demonstrated variability in curriculum, content, and resources. These results support future multidisciplinary efforts to more clearly standardize the fellowship experience in order to ensure practice readiness of these uniquely qualified surgeons., Levels of Evidence: Level V., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Rising costs of living, coupled with housing shortages across the USA, have made housing instability a key issue over the past few years. Alongside this problem has also been a steady rise in violence against (and gun deaths among) Asian Americans. Limited scholarship, however, has examined these issues in the context of this increasingly stigmatised population. The objective of this study was to investigate the association between housing instability and firearm victimisation among Asian Americans. We further assessed how being worried about victimisation may vary by ethnicity., Methods: We conducted secondary data analysis, using the 2021-2022 California Health Interview Survey. We used weighted logistic regression to assess the association between housing instability and firearm victimisation among Asian Americans., Results: Asian respondents experiencing housing instability had significantly greater odds of worrying about firearm victimisation, compared with those with a stable home, even after accounting for various sociodemographic and health-related factors (adjusted OR (AOR)=1.79, p<0.05). Additionally, the odds of being concerned about firearm victimisation were significantly lower among Japanese (AOR=0.64) and Vietnamese (AOR=0.72) participants, compared with Chinese respondents (both p<0.05)., Discussion and Conclusions: Our findings confirm that not having a stable home is strongly linked to worrying about firearm victimisation among Asian Americans. This concern varies significantly by ethnicity. We highlight the importance of disaggregating data on Asian Americans and discuss broader implications for public health., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

While the earliest published health disparity research in the United States dates to 1899, the field was not formally established until the late 20th century. Initially focused on race and ethnicity, the field has broadened to include socioeconomic status. Several measures have been developed to quantify socioeconomic disadvantage, including the Social Vulnerability Index, Area Deprivation Index, and Child Opportunity Index. These indices have been validated and demonstrate correlation with health outcomes. However, socioeconomic status cannot fully explain health inequities experienced by people of minoritized racial and ethnic identities. Three generations of health disparities research have been described-identification of disparities, root analysis, and development of interventions to mitigate health inequities. While there has been an increase in publication of health disparity research, there is little third generation work. It is imperative that health disparities research move beyond defining the problem and toward interventions that will reduce health inequities. LEVELS OF EVIDENCE: Level IV., Competing Interests: Conflicts of interest We have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background & Aims: Acute kidney injury (AKI) in cirrhosis is common and associated with high morbidity, but the incidence rates of different etiologies of AKI are not well described in the US. We compared incidence rates, practice patterns, and outcomes across etiologies of AKI in cirrhosis., Methods: We performed a retrospective cohort study of 11 hospital networks, including consecutive adult patients admitted with AKI and cirrhosis in 2019. The etiology of AKI was adjudicated based on pre-specified clinical definitions (prerenal/hypovolemic AKI, hepatorenal syndrome [HRS-AKI], acute tubular necrosis [ATN], other)., Results: A total of 2,063 patients were included (median age 62 [IQR 54-69] years, 38.3% female, median MELD-Na score 26 [19-31]). The most common etiology was prerenal AKI (44.3%), followed by ATN (30.4%) and HRS-AKI (12.1%); 6.0% had other AKI, and 7.2% could not be classified. In our cohort, 8.1% of patients received a liver transplant and 36.5% died by 90 days. The lowest rate of death was observed in patients with prerenal AKI (22.2%; p <0.001), while death rates were higher but not significantly different from each other in those with HRS-AKI and ATN (49.0% vs. 52.7%; p = 0.42). Using prerenal AKI as a reference, the adjusted subdistribution hazard ratio (sHR) for 90-day mortality was higher for HRS-AKI (sHR 2.78; 95% CI 2.18-3.54; p <0.001) and ATN (sHR 2.83; 95% CI 2.36-3.41; p <0.001). In adjusted analysis, higher AKI stage and lack of complete response to treatment were associated with an increased risk of 90-day mortality (p <0.001 for all)., Conclusion: AKI is a severe complication of cirrhosis. HRS-AKI is uncommon and is associated with similar outcomes to ATN. The etiology of AKI, AKI stage/severity, and non-response to treatment were associated with mortality. Further optimization of vasoconstrictors for HRS-AKI and supportive therapies for ATN are needed., Impact and Implications: Acute kidney injury (AKI) in cirrhosis carries high morbidity, and management is determined by the etiology of injury. However, a large and well-adjudicated multicenter database from US centers that uses updated AKI definitions is lacking. Our findings demonstrate that acute tubular necrosis and hepatorenal syndrome have similar outcomes (∼50% mortality at 90 days), though hepatorenal syndrome is uncommon (12% of all AKI cases). These findings represent practice patterns at US transplant/tertiary centers and can be used as a baseline, presenting the situation prior to the adoption of terlipressin in the US., (Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

To evaluate the image quality, dosimetric properties, setup reproducibility, and planar cine motion detection of a high-resolution brain coil and integrated stereotactic brain immobilization system that constitute a new brain treatment package (BTP) on a low-field magnetic resonance imaging (MRI) linear accelerator (MR-linac). Image quality of the high-resolution brain coil was evaluated with the 17 cm diameter spherical phantom and the American College of Radiology (ACR) Large MRI Phantom. Patient imaging studies approved by the institutional review board (IRB) assisted in selecting image acquisition parameters. Radiographic and dosimetric evaluation of the high-resolution brain coil and the associated immobilization devices was performed using dose calculations and ion chamber measurements. End-to-end testing was performed simulating a cranial lesion in a phantom. Inter-fraction setup variability and motion detection tests were evaluated on four healthy volunteers. Inter-fraction variability was assessed based on three repeat setups for each volunteer. Motion detection was evaluated using three-plane (axial, coronal, and sagittal) MR-cine imaging sessions, where volunteers were asked to perform a set of specific motions. The images were post-processed and evaluated using an in-house program. Contrast resolution of the high-resolution brain coil is superior to the head/neck and torso coils. The BTP receiver coils have an average HU value of 525 HU. The most significant radiation attenuation (3.14%) of the BTP, occurs through the lateral portion of the overlay board where the high-precision lateral-profile mask clips attach to the overlay. The greatest inter-fraction setup variability occurred in the pitch (average 1.08 degree) and translationally in the superior/inferior direction (average 4.88 mm). Three plane cine imaging with the BTP was able to detect large and small motions. Small voluntary motions, sub-millimeter in magnitude (maximum 0.9 mm), from motion of external limbs were detected. Imaging tests, inter-fraction setup variability, attenuation, and end-to-end measurements were quantified and performed for the BTP. Results demonstrate better contrast resolution and low contrast detectability that allows for better visualization of soft tissue anatomical changes relative to head/neck and torso coil systems., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Objective: Magnetic resonance imaging (MRI) is a standard imaging modality in intracranial stereotactic radiosurgery (SRS) for defining target volumes. However, wide disparities in MRI resolution exist, which could directly impact accuracy of target delineation. Here, sequences with various MRI resolution were acquired on phantoms to evaluate the effect on volume definition and dosimetric consequence for cranial SRS., Materials/methods: Four T1-weighted MR sequences with increasing 3D resolution were compared, including two Spin Echo (SE) 2D acquisitions with 5mm and 3mm slice thickness ( SE5mm, SE3mm ) and two gradient echo 3D acquisitions ( TFE, BRAVO ). The voxel sizes were 0.4×0.4×5.0, 0.5×0.5×3.0, 0.9×0.9×1.25, and 0.4×0.4×0.5 mm 3 , respectively. Four phantoms with simulated lesions of different shape and volume (range, 0.53-25.0 cm 3 ) were imaged, resulting in 16 total sets of MRIs. Four radiation oncologists provided contours on individual MR image set. All observer contours were compared with ground truth, defined on CT image according to the absolute dimensions of the target structure, using Dice similarity coefficient ( DSC ), Hausdorff distance ( HD ), mean distance-to-agreement ( MDA ), and the ratio between reconstructed and true volume ( Ratio vol ). For dosimetric consequence, SRS plans targeting observer volumes were created. The true Paddick conformity index ( C I p a d d i c k t r u e ), calculated with true target volume, was correlated with quality of observer volume., Results: All measures of observer contours improved as increasingly higher MRI resolution was provided from SE5mm to BRAVO . The improvement in DSC , HD and MDA was statistically significant (p<0.01). Dosimetrically, C I p a d d i c k t r u e   strongly correlated with DSC of the planning observer volume (Pearson's r=0.94, p<0.00001)., Conclusions: Significant improvement in target definition and reduced inter-observer variation was observed as the MRI resolution improved, which also improved the quality of SRS plans. Results imply that high resolution 3D MR sequences should be used to minimize potential errors in target definition, and multi-slice 2D sequences should be avoided., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Liang, Schaff, Zhao, Snyder, Chetty, Shah and Siddiqui.)

South Asian Americans are part of the fastest growing racial/ethnic group in the United States and make up a substantial portion of the U.S. immigrant population. Research on this group has often focused on acculturation, the adoption of different values and behaviors in a new sociocultural environment. While there is evidence to suggest that acculturation (and the stress associated with this process) has a negative effect on the health and well-being of Asian Americans, more recent research has emphasized the need to examine the role of broader social forces-including everyday racism-in impacting mental health. Drawing on the stress process model, this study uses an original survey instrument to investigate the relationships between acculturative stress, anti-Asian racism, and mental health among a community sample of 200 South Asians in Texas. Results from hierarchical multiple regression models indicate that both acculturative stress and everyday racism are strongly linked to higher levels of anxiety-related symptoms and more frequent depressive symptoms. Everyday racism, however, explained variance in these outcomes, well beyond the effect of acculturative stress and other sociodemographic factors. These results underscore the potential benefit and importance of including questions about racism in community health surveys that aim to study health disparities among Asian Americans and highlight the persistence of social issues that U.S. South Asians face., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Siddiqui.)

Background: Estimating the cumulative incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for setting public health policies. We leveraged deidentified Massachusetts newborn screening specimens as an accessible, retrospective source of maternal antibodies for estimating statewide seroprevalence in a nontest-seeking population., Methods: We analyzed 72 117 newborn specimens collected from November 2019 through December 2020, representing 337 towns and cities across Massachusetts. Seroprevalence was estimated for the Massachusetts population after correcting for imperfect test specificity and nonrepresentative sampling using Bayesian multilevel regression and poststratification., Results: Statewide seroprevalence was estimated to be 0.03% (90% credible interval [CI], 0.00-0.11) in November 2019 and rose to 1.47% (90% CI: 1.00-2.13) by May 2020, following sustained SARS-CoV-2 transmission in the spring. Seroprevalence plateaued from May onward, reaching 2.15% (90% CI: 1.56-2.98) in December 2020. Seroprevalence varied substantially by community and was particularly associated with community percent non-Hispanic Black (β = .024; 90% CI: 0.004-0.044); i.e., a 10% increase in community percent non-Hispanic Black was associated with 27% higher odds of seropositivity. Seroprevalence estimates had good concordance with reported case counts and wastewater surveillance for most of 2020, prior to the resurgence of transmission in winter., Conclusions: Cumulative incidence of SARS-CoV-2 protective antibody in Massachusetts was low as of December 2020, indicating that a substantial fraction of the population was still susceptible. Maternal seroprevalence data from newborn screening can inform longitudinal trends and identify cities and towns at highest risk, particularly in settings where widespread diagnostic testing is unavailable., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Although studies have shown that discrimination is linked to poor mental health, less is known about this relationship in the context of healthcare and how it varies for different Asian subgroups. The aim of this study was to examine the relationships between mistreatment in medical care and psychological distress among a diverse sample of Asian Americans. Data were drawn from the 2015-2017 California Health Interview Survey. A series of regression models were estimated to test the association between mistreatment in medical care and psychological distress. Various Asian subgroups showed different levels of psychological distress. Mistreatment in medical care was also linked to worse mental health. Findings, however, did not show significant differences in the interaction between mistreatment and ethnicity on psychological distress. This study advances knowledge on the experiences of Asian Americans and contributes to the literature showing the impact of discrimination on mental health., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

As public health guidelines throughout the world have relaxed in response to vaccination campaigns against SARS-CoV-2, it is likely that SARS-CoV-2 will remain endemic, fueled by the rise of more infectious SARS-CoV-2 variants. Moreover, in the setting of waning natural and vaccine immunity, reinfections have emerged across the globe, even among previously infected and vaccinated individuals. As such, the ability to detect reexposure to and reinfection by SARS-CoV-2 is a key component for global protection against this virus and, more importantly, against the potential emergence of vaccine escape mutations. Accordingly, there is a strong and continued need for the development and deployment of simple methods to detect emerging hot spots of reinfection to inform targeted pandemic response and containment, including targeted and specific deployment of vaccine booster campaigns. In this study, we identify simple, rapid immune biomarkers of reinfection in rhesus macaques, including IgG3 antibody levels against nucleocapsid and FcγR2A receptor binding activity of anti-RBD antibodies, that are recapitulated in human reinfection cases. As such, this cross-species analysis underscores the potential utility of simple antibody titers and function as price-effective and scalable markers of reinfection to provide increased resolution and resilience against new outbreaks. IMPORTANCE As public health and social distancing guidelines loosen in the setting of waning global natural and vaccine immunity, a deeper understanding of the immunological response to reexposure and reinfection to this highly contagious pathogen is necessary to maintain public health. Viral sequencing analysis provides a robust but unrealistic means to monitor reinfection globally. The identification of scalable pathogen-specific biomarkers of reexposure and reinfection, however, could significantly accelerate our capacity to monitor the spread of the virus through naive and experienced hosts, providing key insights into mechanisms of disease attenuation. Using a nonhuman primate model of controlled SARS-CoV-2 reexposure, we deeply probed the humoral immune response following rechallenge with various doses of viral inocula. We identified virus-specific humoral biomarkers of reinfection, with significant increases in antibody titer and function upon rechallenge across a range of humoral features, including IgG1 to the receptor binding domain of the spike protein of SARS-CoV-2 (RBD), IgG3 to the nucleocapsid protein (N), and FcγR2A receptor binding to anti-RBD antibodies. These features not only differentiated primary infection from reexposure and reinfection in monkeys but also were recapitulated in a sequencing-confirmed reinfection patient and in a cohort of putatively reinfected humans that evolved a PCR-positive test in spite of preexisting seropositivity. As such, this cross-species analysis using a controlled primate model and human cohorts reveals increases in antibody titers as promising cross-validated serological markers of reinfection and reexposure.

Identifying the potential for SARS-CoV-2 reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4,411 United States employees in 4 states between April 2020 and February 2021. We conducted a multivariable logistic regression investigating the association between baseline serological status and subsequent PCR test result in order to calculate an odds ratio for reinfection. We estimated an odds ratio for reinfection ranging from 0.14 (95% CI: 0.019 to 0.63) to 0.28 (95% CI: 0.05 to 1.1), implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 72% to 86% reduced odds of a subsequent PCR positive test based on our point estimates. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a 6-month time period. We also highlight 2 major sources of bias and uncertainty to be considered when estimating the relative risk of reinfection, confounders and the choice of baseline time point, and show how to account for both in reinfection analysis., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: GA is a founder of Seromyx Systems Inc., a company developing platform technology that describes the antibody immune response. GA’s interests were reviewed and are managed by Massachusetts General Hospital in accordance with their conflict-of-interest policies. MJG, SB, DD, YH, JR, EP, BM, ASM, and ERM are employees of Space Exploration Technologies Corp. All other authors have declared that no conflict of interest exists.

Obesity is a key correlate of severe SARS-CoV-2 outcomes while the role of obesity on risk of SARS-CoV-2 infection, symptom phenotype, and immune response remain poorly defined. We examined data from a prospective SARS-CoV-2 cohort study to address these questions. Serostatus, body mass index, demographics, comorbidities, and prior COVID-19 compatible symptoms were assessed at baseline and serostatus and symptoms monthly thereafter. SARS-CoV-2 immunoassays included an IgG ELISA targeting the spike RBD, multiarray Luminex targeting 20 viral antigens, pseudovirus neutralization, and T cell ELISPOT assays. Our results from a large prospective SARS-CoV-2 cohort study indicate symptom phenotype is strongly influenced by obesity among younger but not older age groups; we did not identify evidence to suggest obese individuals are at higher risk of SARS-CoV-2 infection; and remarkably homogenous immune activity across BMI categories suggests immune protection across these groups may be similar.

Presurgical devascularization of neoplasms of the head and neck can be achieved by endovascular as well as direct percutaneous embolization techniques. We report a case of percutaneous glue embolization of an orbital meningioma, complicated by delayed acute stroke due to the distal migration of polymerized glue in the left middle cerebral artery. To the best of our knowledge, this is the first report to discuss the percutaneous embolization of orbital meningioma complicated by stroke due to intracranial glue migration., Competing Interests: None

Antibodies serve as biomarkers of infection, but if sustained can confer long-term immunity. Yet, for most clinically approved vaccines, binding antibody titers only serve as a surrogate of protection. Instead, the ability of vaccine induced antibodies to neutralize or mediate Fc-effector functions is mechanistically linked to protection. While evidence has begun to point to persisting antibody responses among SARS-CoV-2 infected individuals, cases of re-infection have begun to emerge, calling the protective nature of humoral immunity against this highly infectious pathogen into question. Using a community-based surveillance study, we aimed to define the relationship between titers and functional antibody activity to SARS-CoV-2 over time. Here we report significant heterogeneity, but limited decay, across antibody titers amongst 120 identified seroconverters, most of whom had asymptomatic infection. Notably, neutralization, Fc-function, and SARS-CoV-2 specific T cell responses were only observed in subjects that elicited RBD-specific antibody titers above a threshold. The findings point to a switch-like relationship between observed antibody titer and function, where a distinct threshold of activity-defined by the level of antibodies-is required to elicit vigorous humoral and cellular response. This response activity level may be essential for durable protection, potentially explaining why re-infections occur with SARS-CoV-2 and other common coronaviruses.

Purpose: Treatment planning of skull based meningiomas can be difficult due to the irregular shaped target volumes and proximity to critical optic structures. This study evaluated the use of HyperArc (HA) radiosurgery optimization and delivery in conjunction with multicriteria optimization (MCO) to create conformal and efficient treatment plans for conventionally fractionated radiation therapy to difficult base-of-skull (BOS) lesions., Methods and Materials: Twelve patients with BOS meningioma were retrospectively planned with HA-specific optimization algorithm, stereotactic normal tissue objective (SRS-NTO), and conventional automatic normal tissue objective to evaluate normal brain sparing (mean dose and V20 Gy). MCO was used on both SRS-NTO and automatic normal tissue objective plans to further decrease organ-at-risk doses and target dose maximum to within clinically acceptable constraints. Delivery efficiency was evaluated based on planned monitor units., Results: The SRS-NTO in HA can be used to improve the mid- and low-dose spread to normal brain tissue in the irradiation of BOS meningiomas. Improvement in normal brain sparing can be seen in larger, more irregular shaped lesions and less so in smaller spherical targets. MCO can be used in conjunction with the SRS-NTO to reduce target dose maximum and dose to organ at risk without sacrificing the gain in normal brain sparing., Conclusions: HA can be beneficial both in treatment planning by using the SRS-NTO and in delivery efficiency through the decrease in monitor units and automated delivery.

SARS-CoV-2 has a positive sense RNA genome of 29.9 kb in size, showing high sequence similarity to the BAT-CoV, SARS-CoV, MERS-CoV. SARS-CoV-2 is composed of 14 open reading frames (ORFs), which encodes for a total of 27 proteins divided into structural and non-structural proteins (NSPs). The fundamental structural protein-encoding genes are a spike protein (S) gene, envelope protein (E) gene, a membrane protein (M) gene, and a nucleocapsid protein (N) gene. They make about 33% of the entire genome and are vital for the viral life cycle. Rest 67% is distributed among different NSPs (such as M pro , helicase, and RNA-dependent RNA polymerase) encoding genes across the ORFs, which are involved in virus-cell receptor interactions during viral entry. Researchers are trying to formulate vaccines, therapeutic antibodies or protein-targeted antiviral drugs to control the spread. This review proceeds stepwise through the COVID-19 outbreak, structural and genomic organization, entry mechanism, pathogenesis, and finally highlighting the essential proteins involved at each step that might be potential targets for drug discovery. Currently, approved treatment modalities consist of only supportive care and oxygen supplementation. This review is established on the current knowledge that has expanded on structural motifs and topology of proteins and their functions., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Microtubule affinity-regulating kinase 4 (MARK4), a member of the serine/threonine kinase family, is an emerging therapeutic target in anticancer drug discovery paradigm due to its involvement in regulation of microtubule dynamics, cell cycle regulation, and cancer progression. Therefore, to identify the novel chemical architecture for the design and development of novel MARK4 inhibitors with concomitant radical scavenging property, a series of small-molecule arylaldoxime/5-nitroimidazole conjugates were designed and synthesized via multistep chemical reactions following the pharmacophoric hybridization approach. Compound 4h was identified as a promising MARK4 inhibitor with high selectivity toward MARK4 inhibition as compared to the panel of screened 30 kinases pertaining to the serine/threonine family, which was validated by molecular docking and fluorescence binding studies. The comprehensive cell-based examination divulged the promising apoptotic, antiproliferative, and antioxidant potential for the chemotype 4h . The compound 4h was endowed with the K a value of 3.6 × 10 3 M -1 for human serum albumin, which reflects its remarkable transportation and delivery properties to the target site via blood. The present study impedes that in the future, such compounds may stand as optimized pharmacological lead candidates in drug discovery for targeting cancer via MARK4 inhibition with a remarkable anticancer profile., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Background/purpose: Surgical management of appendicitis accounts for ~30% of total expenditure in the practice of pediatric surgery and is associated with high cost variation. We hypothesize that incorporating single-incision laparoscopy (SILS) and the resultant by-product dual-incision laparoscopy (DILS) into a historically three-incision laparoscopic (TILS) appendectomy practice affords equal outcomes at lower cost., Methods: Appendectomies performed at a large-volume tertiary care children's hospital from 1/2015-12/2017 were retrospectively reviewed. Appendectomy technique and appendicitis severity were stratified against operative and admission direct variable (DV) costs. Secondary outcomes included perioperative time course and 30-day postoperative outcomes., Results: A total of 970 appendectomies were analyzed during the study period (61% acute, 39% complex appendicitis). SILS and DILS had significantly lower mean DV costs and OR times compared to TILS for both acute and complex appendicitis while maintaining equivalent outcomes., Conclusions: SILS and DILS appendectomy techniques can be incorporated into pediatric surgical practice at lower cost than TILS appendectomy while maintaining equivalent outcomes. Further, the introduction of a tiered approach to laparoscopic appendectomy, in which all cases are started as SILS with additional incisions added based on operative difficulty, is estimated to save $74,580 annually in operative DV costs at a pediatric surgical center averaging 314 laparoscopic appendectomies per year., Type of Study: Treatment Study., Level of Evidence: Level III., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The theta rhythm-a slow (6-12 Hz) oscillatory component of the local field potential-plays a critical role in spatial navigation and memory by coordinating the activity of neuronal ensembles within the medial temporal lobe (MTL). Although theta has been extensively studied in freely moving rodents, its presence in humans has been elusive and primarily investigated in stationary subjects. Here we used a unique clinical opportunity to examine theta within the human MTL during untethered, real-world ambulatory movement. We recorded intracranial electroencephalographic activity from participants chronically implanted with the wireless NeuroPace responsive neurostimulator (RNS) and tracked their motion with sub-millimeter precision. Our data revealed that movement-related theta oscillations indeed exist in humans, such that theta power is significantly higher during movement than immobility. Unlike in rodents, however, theta occurs in short bouts, with average durations of ∼400 ms, which are more prevalent during fast versus slow movements. In a rare opportunity to study a congenitally blind participant, we found that both the prevalence and duration of theta bouts were increased relative to the sighted participants. These results provide critical support for conserved neurobiological characteristics of theta oscillations during ambulatory spatial navigation, while highlighting some fundamental differences across species in these oscillations between humans and rodents., (Published by Elsevier Ltd.)

Purpose: To investigate pulmonary metabolic alterations during progression of acute lung injury., Methods: Using hyperpolarized [1- 13 C] pyruvate imaging, we measured pulmonary lactate and pyruvate in 15 ventilated rats 1, 2, and 4 h after initiation of mechanical ventilation. Lung compliance was used as a marker for injury progression. 5 untreated rats were used as controls; 5 rats (injured-1) received 1 ml/kg and another 5 rats (injured-2) received 2 ml/kg hydrochloric acid (pH 1.25) in the trachea at 70 min., Results: The mean lactate-to-pyruvate ratio of the injured-1 cohort was 0.15 ± 0.02 and 0.15 ± 0.03 at baseline and 1 h after the injury, and significantly increased from the baseline value 3 h after the injury to 0.23 ± 0.02 (P = 0.002). The mean lactate-to-pyruvate ratio of the injured-2 cohort decreased from 0.14 ± 0.03 at baseline to 0.08 ± 0.02 1 h after the injury and further decreased to 0.07 ± 0.02 (P = 0.08) 3 h after injury. No significant change was observed in the control group. Compliance in both injured groups decreased significantly after the injury (P < 0.01)., Conclusions: Our findings suggest that in severe cases of lung injury, edema and hyperperfusion in the injured lung tissue may complicate interpretation of the pulmonary lactate-to-pyruvate ratio as a marker of inflammation. However, combining the lactate-to-pyruvate ratio with pulmonary compliance provides more insight into the progression of the injury and its severity. Magn Reson Med 78:2106-2115, 2017. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

The purpose of this study was to develop metrics to evaluate uncertainties in deformable dose accumulation for patients with non-small cell lung cancer (NSCLC). Initial treatment plans (primary) and cone-beam CT (CBCT) images were retrospectively processed for seven NSCLC patients, who showed significant tumor regression during the course of treatment. Each plan was developed with IMRT for 2 Gy  ×  33 fractions. A B-spline-based DIR algorithm was used to register weekly CBCT images to a reference image acquired at fraction 21 and the resultant displacement vector fields (DVFs) were then modified using a finite element method (FEM). The doses were calculated on each of these CBCT images and mapped to the reference image using a tri-linear dose interpolation method, based on the B-spline and FEM-generated DVFs. Contours propagated from the planning image were adjusted to the residual tumor and OARs on the reference image to develop a secondary plan. For iso-prescription adaptive plans (relative to initial plans), mean lung dose (MLD) was reduced, on average from 17.3 Gy (initial plan) to 15.2, 14.5 and 14.8 Gy for the plans adapted using the rigid, B-Spline and FEM-based registrations. Similarly, for iso-toxic adaptive plans (considering MLD relative to initial plans) using the rigid, B-Spline and FEM-based registrations, the average doses were 69.9  ±  6.8, 65.7  ±  5.1 and 67.2  ±  5.6 Gy in the initial volume (PTV 1 ), and 81.5  ±  25.8, 77.7  ±  21.6, and 78.9  ±  22.5 Gy in the residual volume (PTV 21 ), respectively. Tumor volume reduction was correlated with dose escalation (for isotoxic plans, correlation coefficient  =  0.92), and with MLD reduction (for iso-fractional plans, correlation coefficient  =  0.85). For the case of the iso-toxic dose escalation, plans adapted with the B-Spline and FEM DVFs differed from the primary plan adapted with rigid registration by 2.8  ±  1.0 Gy and 1.8  ±  0.9 Gy in PTV 1 , and the mean difference between doses accumulated using the B-spline and FEM DVF's was 1.1  ±  0.6 Gy. As a dose mapping-induced energy change, energy defect in the tumor volume was 20.8  ±  13.4% and 4.5  ±  2.4% for the B-spline and FEM-based dose accumulations, respectively. The energy defect of the B-Spline-based dose accumulation is significant in the tumor volume and highly correlated to the difference between the B-Spline and FEM-accumulated doses with their correlation coefficient equal to 0.79. Adaptive planning helps escalate target dose and spare normal tissue for patients with NSCLC, but deformable dose accumulation may have a significant loss of energy in regressed tumor volumes when using image intensity-based DIR algorithms. The metric of energy defect is a useful tool for evaluation of adaptive planning accuracy for lung cancer patients.

Background: In 2011, road traffic injury-associated fatalities among motorized two-wheeler (MTW) pillion riders (backseat two-wheeler passengers) rose 30% in Karachi. Despite mandatory helmet laws, helmet use fell 20% the same year. This study aims to identify opinions of female pillions on helmet usage and whether various forms of media influence their self-perception., Methods: Trained surveyors, using a survey tool used in similar studies in South Asia, conducted random, man-on-the-street interviews of 400 women in four areas of Karachi. Data pertaining to demographics, opinions on helmet laws, media influences, and helmet usage were collected. Data were analyzed in SAS 9.3 using chi-squared or Fisher's exact tests., Results: Of the 400 women, 98.8% (n = 394) reported never wearing a helmet while riding on a MTW as a pillion rider. Women with a postsecondary or higher (US ninth grade) education level were more likely to be aware of helmet laws (38.6%) than women with lower education levels (24.6%, P = 0.005). Most women (82.4%, n = 329) supported mandatory laws and 97% (n = 289) recognized that disability was the more likely to result than death in event of a traumatic brain injury. Nearly all (98.5%, n = 394) stated that they would use a helmet if they were men, regardless of age, education level, or employment status. Television news was the most influential media form (83.7%, n = 334), with most women finding it effective because of its informative nature (91.3%, n = 303)., Conclusions: Most Pakistani women do not personally use helmets when riding MTWs, yet most believe helmet use should be legally required for MTW riders and drivers. These data show that media outlets such as television can be used as a platform to educate the public about helmet usage, which may lead to improved helmet compliance among female MTW pillions in Pakistan. Furthermore, investigations into improved helmet comfort and appearance by collaborating with helmet manufacturers may have a positive impact on helmet use in Pakistan., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In continuation of our previous work, a series of furan-thiazolidinone hybrids was prepared by Knoevenagel condensation of 3-(furan-2-ylmethyl)-2-(phenylimino)-1, 3-thiazolidin-4-one with different aryl aldehydes in presence of strong base. Some members of the series exhibited remarkable antiamoebic activity and cell viability. Three compounds (3, 6 and 11) showed excellent binding energy for Entamoeba histolytica O-acetyle-l-serine sulfohydrolase and Entamoeba histolytica thioredoxin reductase. These compounds demonstrated significant inhibition of O-acetyle-l-serine sulfohydrolase. The promising antiamoebic activity and enzymatic assay of 3, 6 and 11 make them promising molecules for further lead optimization in the development of novel antiamoebic agents., (Copyright © 2016. Published by Elsevier Masson SAS.)

Background: Motorized two-wheelers (MTWs) such as scooters and motorcycles place drivers and passengers at significant risk of injury and death in the event of a road traffic accident. In India, where road traffic is poorly regulated and consists of vehicles ranging from semitrucks to animal carts, the MTW pillion rider (backseat passenger) is particularly vulnerable. Annually, approximately 140,000 Indians are injured or killed in MTW road traffic accidents. In 2011, the city of New Delhi renewed a mandatory helmet use exemption for its 8 million women. We sought to identify the patterns of injury among MTW pillion riders in the city of New Delhi, including differences between helmeted and unhelmeted male and female pillion riders., Methods: All records of incoming trauma patients to the Jai Prakash Narayan Apex Trauma Center, New Delhi, were reviewed for the 23-mo period from April 1, 2009 until March 1, 2011. More than 3000 charts were reviewed selecting for patients who were MTW pillion riders involved in road traffic accidents. Data including Glasgow Coma Scale score, number of surgical procedures performed, length of stay, and demographic information were collected from charts that met the criteria. Fisher's exact test was used for categorical variables and Kruskal-Wallis test for continuous variables., Results: A total of 466 charts of MTW pillions in road traffic accidents were identified with 108 helmeted males, 161 unhelmeted males, three helmeted females, and 194 unhelmeted females. Females, both unhelmeted and helmeted, were more likely to have head and neck injury than unhelmeted males or helmeted males (66.0% and 66.7% versus 53.4% and 27.8%, P < 0.001). Unhelmeted females were most likely to suffer inhospital mortality (17.6%, P = 0.008) and require intensive care unit admission (40.0%, P = 0.004). Unhelmeted pillions, both male and female, had significantly lower Glasgow Coma Scale scores than helmeted pillions (12.6 and 12.8 versus 13.8 and 15, P = 0.04)., Conclusions: Female pillions are more likely to have head and neck injury than male pillions, and unhelmeted pillions are more likely to have injuries resulting in their death. This firmly establishes the protective benefit of helmet use for pillions. Encouraging helmet use among all pillions may prevent a significant number of injuries and deaths, and mandatory helmet laws may decrease morbidity and mortality of MTW road traffic accidents for the women of New Delhi and all of India., (Copyright © 2016 Elsevier Inc. All rights reserved.)

2.5 MV electronic portal imaging, available on Varian TrueBeam machines, was characterized using various phantoms in this study. Its low-contrast detectability, spatial resolution, and contrast-to-noise ratio (CNR) were compared with those of conventional 6 MV and kV planar imaging. Scatter effect in large patient body was simulated by adding solid water slabs along the beam path. The 2.5 MV imaging mode was also evaluated using clinically acquired images from 24 patients for the sites of brain, head and neck, lung, and abdomen. With respect to 6 MV, the 2.5 MV achieved higher contrast and preserved sharpness on bony structures with only half of the imaging dose. The quality of 2.5 MV imaging was comparable to that of kV imaging when the lateral separation of patient was greater than 38 cm, while the kV image quality degraded rapidly as patient separation increased. Based on the results of patient images, 2.5 MV imaging was better for cranial and extracranial SRS than the 6 MV imaging., (© 2016 The Authors.)

Metronidazole hydrazone conjugates (2-13) were synthesized and screened in vitro for antiamoebic activity against HM1: IMSS strain of Entamoeba histolytica. Six compounds were found to be better inhibitors of E. histolytica than the reference drug metronidazole. These compounds showed greater than 50-60% viability against HeLa cervical cancer cell line after 72 h treatment. Also, molecular docking study was undertaken on E. histolytica thioredoxin reductase (EhTHRase) protein which showed significant binding affinity in the active site. Out of the six actives, some of the compounds showed lipophilic characteristics., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Catheter associated blood stream infections (CABSIs) are morbid and expensive for all ages, including neonates. Thus far, the impact of CABSI prevention protocols, such as insertion and maintenance bundles, in the neonatal intensive care unit (NICU) is largely unknown. We hypothesized that lines placed in the operating room (OR) would have a lower infection rate due to established insertion protocols and a more sterile environment., Methods: A retrospective chart review of NICU patients who received a percutaneous or tunneled central venous catheter between 2005 and 2012 was performed. ECMO cannulas, PICC and umbilical catheters were excluded. Variables of interest included demographics, anatomical site, hospital location, line days, and line infection. Line infection was defined as a positive blood culture drawn through the catheter., Results: A total of 368 catheters were placed in 285 NICU patients. Majority of catheters (65.5%) were placed in OR. Saphenous and femoral veins were most common anatomical sites (50.8%). Twenty-eight catheters were infected (7.6%). After adjusting for preoperative antibiotics, anatomical site, and SNAPPE-II scores, lines placed in OR were three times less likely to become infected (Odds Ratio=0.32, p=0.038). Although implementation of CABSI prevention protocols resulted in statistically significant reductions in infection (Odds Ratio=0.4, p=0.043), lines placed in the OR remained less likely to become infected., Conclusions: NICU line infection rates decreased with implementation of CABSI prevention protocols. Despite this implementation, catheters placed in the NICU continued to have higher infection rates. As a result, when patient status allows it, we recommend that central lines in newborns be placed in the operating room., (Copyright © 2015 Elsevier Inc. All rights reserved.)

An in-house database of 520 compounds was docked against Entamoeba histolytica thioredoxin reductase (EhTrR), a promising target for the treatment of amoebiasis. Amongst these, some metronidazole (MTZ)-triazole hybrids were ranked high, with docking scores from -10.23 to -7.56. Studies of the binding orientations and conformations show that the head groups of MTZ-triazole hybrids interact with the arginine residues within the binding pocket of EhTrR, making it clear that such is the optimal and most reliable orientation for this class of compounds. The top-ten MTZ-triazole hybrids were then selected for evaluation of their activity against the HM1:IMSS strain of amoeba. The most active compound, 2-pyridyl-(1,2,3-triazolyl)metronidazole 10, with an IC50 value of 8.4 nM, was significantly more active than the standard drug MTZ alone. Docking studies revealed that compound 10 may act as an EhTrR inhibitor with activity in the nanomolar range and satisfactory ADME properties; it is a suitable candidate to be carried forward as a potential lead in the discovery of drugs to combat amoebiasis., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

N-Acylhydrazones derived from 7-chloro-4-piperazin-1-yl-quinoline were synthesized and biologically evaluated for blood-stage of Plasmodium falciparum and Entamoeba histolytica trophozoites. N-Acylhydrazone F12 was found to inhibit the P. falciparum growth as well as its life cycle with good selectivity, which was achieved by inhibiting hematin formation. Compound F24 showed better IC50 value than the amoebicidal drug metronidazole., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

A series of 1,2,4-triazole derivatives containing thiosemicarbazone linkage was synthesized and evaluated for their in vitro antiamoebic activity against HM1:IMSS strain of Entamoeba histolytica. All the compounds were capable of inhibiting the growth of E. histolytica out of which four compounds (IC(50)=0.28-1.38 μM) were found to have better efficacy than the standard drug Metronidazole (IC(50)=1.8 μM). Cytotoxicity of the active compounds was assessed by MTT assay using human breast cancer MCF-7 cell line, which revealed that all the compounds were low cytotoxic in the concentration range of 2.5-250 μM., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Osteoarthritis (OA) is a degenerative disease of the joints and results in changes in the biochemical composition of cartilage. Previous studies have been undertaken that have used high-resolution NMR spectroscopy to study the biochemical composition of porcine, canine and bovine cartilage. In the present study, high-resolution magical angle spinning (HR-MAS) NMR spectroscopy at 11.7 T has been used to characterize metabolites and detect differences in the spectral signature of human knee articular cartilage from non-OA healthy cadaver knees and samples acquired from severe OA patients at the time of total knee replacement surgery. A statistically significant difference in the alanine (1.47 p.p.m.), N-acetyl (2.04 p.p.m.), choline (3.25 p.p.m.) and glycine (3.55 p.p.m.) metabolite levels was observed between healthy and OA specimens. The results of the present study indicate that a decrease in the intensity of N-acetyl resonance occurs in the later stages of OA. A positive correlation of the N-acetyl levels as measured by (1)H HR-MAS NMR spectroscopy with the total proteoglycan content in the same cartilage specimens as measured by the glycosaminoglycan (GAG) assay was observed. This indicates that N-acetyl can serve as an important bio-marker of OA disease progression. A decrease in the alanine concentration in OA may be attributed to the degradation of the collagen framework with disease progression and eventual loss of the degradation products that are transported from cartilage into the synovial cavity., (Copyright © 2011 John Wiley & Sons, Ltd.)

In an effort to develop effective antiamoebic agents, some hydrazones and azoles containing pyridyl moiety were synthesized and screened for in vitro antiamoebic activity against HM1:IMSS strain of Entamoeba histolytica. Among all the compounds, only five compounds (1, 3, 5, 9 and 11) were found to be better inhibitors of growth of E. histolytica than the reference drug metronidazole. The cytotoxic studies of these compounds on human breast cancer MCF-7 cell line revealed that all the compounds were low-cytotoxic in the concentration range of 2.5-250 μM., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

We present a case of a child with an ingested lithium battery causing esophageal perforation with mediastinal injury extending to the pleural cavity. During the endoscopic retrieval of the battery, the child developed the rare complication of subcutaneous emphysema, tension pneumothorax, and pneumomediastinum from excessive iatrogenic air insufflation. The patient developed mediastinitis and had a complicated postoperative course.

The aim of the current study was to determine the effects and the mechanisms of inclusion of dietary whey protein, high calcium, and high vitamin D intake with either a high-sucrose or high-fat base diets on body composition of rodents. Male Wistar rats were assigned to either no whey protein, suboptimal calcium (0.25%), and vitamin D (400 IU/kg) diet (LD), or a diet containing whey protein, high calcium (1.5%), and vitamin D (10 000 IU/kg) diet (HD), and either high-fat (40% of energy) or high-sucrose (60%) base diets for 13 weeks. Liver tissue homogenates were used to determine [(14)C]glucose and [(14)C]palmitate oxidation. mRNA expression of enzymes related to energy metabolism in liver, adipose, and muscle, as well as regulators of muscle mass and insulin receptor was assessed. The results demonstrated that there was reduced accumulation of body fat mass (P = .01) and greater lean mass (P = .03) for the HD- compared to LD-fed group regardless of the background diet. There were no consistent differences between the LD and HD groups across background diets in substrate oxidation and mRNA expression for enzymes measured that regulate energy metabolism, myostatin, or muscle vascular endothelial growth factor. However, there was an increase in insulin receptor mRNA expression in muscle in the HD compared to the LD groups. In conclusion, elevated whey protein, calcium, and vitamin D intake resulted in reduced accumulation of body fat mass and increased lean mass, with a commensurate increase in insulin receptor expression, regardless of the level of calories from fat or sucrose.

Machines of protein destruction-including energy-dependent proteases and disassembly chaperones of the AAA(+) ATPase family-function in all kingdoms of life to sculpt the cellular proteome, ensuring that unnecessary and dangerous proteins are eliminated and biological responses to environmental change are rapidly and properly regulated. Exciting progress has been made in understanding how AAA(+) machines recognize specific proteins as targets and then carry out ATP-dependent dismantling of the tertiary and/or quaternary structure of these molecules during the processes of protein degradation and the disassembly of macromolecular complexes.

ClpX and related AAA+ ATPases of the Clp/Hsp100 family are able to denature native proteins. Here, we explore the role of protein stability in ClpX denaturation and subsequent ClpP degradation of model substrates bearing ssrA degradation tags at different positions. ClpXP degraded T. thermophilus RNase-H* with a C-terminal ssrA tag very efficiently, despite the very high global stability of this thermophilic protein. In fact, global thermodynamic stability appears to play little role in susceptibility to degradation, as a far less stable RNase-H*-ssrA mutant was degraded more slowly than wild type by ClpXP and a completely unfolded mutant variant was degraded less than twice as fast as the wild-type parent. When ssrA peptide tags were covalently linked to surface cysteines at positions 114 or 140 of RNase-H*, the conjugates were proteolyzed very slowly. This resistance to degradation was not caused by inaccessibility of the ssrA tag or an inability of ClpXP to degrade proteins with side-chain linked ssrA tags. Our results support a model in which ClpX denatures proteins by initially unfolding structural elements attached to the degradation tag, suggest an important role for the position of the degradation tag and direction of force application, and correlate well with the mapping of local protein stability within RNase-H* by native-state hydrogen exchange.

ClpX binds substrates bearing specific classes of peptide signals, denatures these proteins, and translocates them through a central pore into ClpP for degradation. ClpX with the V154F po e mutation is severely defective in binding substrates bearing C-motif 1 degradation signals and is also impaired in a subsequent step of substrate engagement. In contrast, this mutant efficiently processes substrates with other classes of recognition signals both in vitro and in vivo. These results demonstrate that the ClpX pore functions in the recognition and catalytic engagement of specific substrates, and that ClpX recognizes different substrate classes in at least two distinct fashions.

ClpXP is an ATP-dependent protease that denatures native proteins and translocates the denatured polypeptide into an interior peptidase chamber for degradation. To address the mechanism of these processes, Arc repressor variants with dramatically different stabilities and unfolding half-lives varying from months to seconds were targeted to ClpXP by addition of the ssrA degradation tag. Remarkably, ClpXP degraded each variant at a very similar rate and hydrolyzed approximately 150 molecules of ATP for each molecule of substrate degraded. The hyperstable substrates did, however, slow the ClpXP ATPase cycle. These results confirm that ClpXP uses an active mechanism to denature its substrates, probably one that applies mechanical force to the native structure. Furthermore, the data suggest that denaturation is inherently inefficient or that significant levels of ATP hydrolysis are required for other reaction steps. ClpXP degraded disulfide-cross-linked dimers efficiently, even when just one subunit contained an ssrA tag. This result indicates that the pore through which denatured proteins enter the proteolytic chamber must be large enough to accommodate simultaneous passage of two or three polypeptide chains.

Setting: While culture filtrate proteins (CFPs) of Mycobacterium tuberculosis appear to be good vaccine candidates for tuberculosis, only CFPs derived from certain popular laboratory strains of M. tuberculosis have been studied for this purpose., Objective: To compare the relative efficacies of CFP preparations from two laboratory strains and four contemporary clinical isolates of M. tuberculosis to induce T-cell activation., Design: CFPs were isolated from six strains of M. tuberculosis and were used to induce 1) T-cell proliferation, 2) IFN-gamma secretion, and 3) IL-12 secretion from peripheral blood derived mononuclear cell (PBMC) preparations from 33 healthy donors., Results: Significant amounts of IL-12 were spontaneously secreted by PBMC preparations; CFP preparations from two clinical isolates (JNU-7 and JNU-51) significantly boosted this response. All six CFP preparations induced IFN-gamma secretion by PBMCs, but those from two contemporary strains of M. tuberculosis (JNU-7 and JNU-22) were most effective in this regard. The effect of CFPs from JNU-7 and JNU-22 was significantly better than those from the laboratory strains (H37Ra and Erdman). Similar results were obtained with the T-cell proliferation parameter., Conclusion: These results suggest that CFPs derived from selected clinical isolates of M. tuberculosis may outperform those of standard laboratory strains, and may therefore be a better source of potential candidates for a tuberculosis vaccine.

Repeated ip administration of hydroquinone (10 mg/kg/day), benzoquinone (2 mg/kg/day) or benzenetriol (6.25 mg/kg/day) to rats for 6 weeks produced significant decreases in RBC and bone marrow cell counts and hemoglobin content, together with relative changes in organ weights. In addition, benzoquinone and benzenetriol elicited histological injuries in liver, thymus, spleen, kidney and peripheral lymph nodes which warrant further investigation.

The effect of a single dose of benzene (0.5 ml/kg body wt i.p.) on the heme saturation of tryptophan pyrrolase activity in liver was examined. There was a significant decrease in the heme saturation of hepatic tryptophan pyrrolase, suggesting depletion of "regulatory heme". After benzene administration there was significant increase in delta-aminolevulinate (ALA) synthetase activity (approx. 2-fold) while delta-aminolevulinate dehydratase activity was significantly decreased, however, ferrochelatase and heme oxygenase activities were unaltered. Administration of tryptophan to benzene pretreated rats showed a reversal of benzene effects on heme synthesizing enzymes: there is an increase in the heme saturation of tryptophan pyrrolase and decrease in delta-aminolevulinate synthetase. However, there was no significant alteration in the activity of delta-aminolevulinate dehydratase.