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Introduction: Chronic kidney disease (CKD) is a severe, progressive condition with a significant economic burden. We performed a systematic review to assess the cost-effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors in treating CKD., Methods: A comprehensive search was conducted across PubMed, Embase, Web of Science, Scopus, INAHTA, NHS EED, and relevant websites. Two reviewers independently screened titles and abstracts, extracted data, and assessed study quality using CHEERS 2022 and Phillips's checklist., Results: Thirteen model-based cost-utility studies met the inclusion criteria, evaluating Empagliflozin ( n  = 3), Canagliflozin ( n  = 3), and Dapagliflozin ( n  = 8). Empagliflozin or Dapagliflozin plus standard care (SoC) was cost-effective compared to SoC alone in CKD patients, regardless of type 2 diabetes (T2D) status. In CKD patients with T2D, SGLT2 inhibitors combined with SoC were cost-saving in high-income countries under health system perspective whereas Dapagliflozin was not cost-effective compared to Canagliflozin. No study met all criteria of the CHEERS 2022 checklist, and most did not fully satisfy Phillips's checklist for economic models., Conclusion: Adding SGLT2 inhibitors to SoC is cost-saving for treating CKD with T2D and cost-effective for CKD patients with or without T2D., Registration: The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023469005.

Background: Medication errors significantly compromise patient safety in emergency departments. Although previous studies have investigated the prevalence of these errors in this setting, results have varied widely., Aim: The aim was to report pooled data on the prevalence and severity of medication errors in emergency departments, as well as the proportion of patients affected by these errors., Method: Systematic searches were conducted in Embase, PubMed, and the Cochrane Library from database inception until June 2023. Studies provided numerical data on medication errors within emergency departments were eligible for inclusion. Random-effects meta-analysis was employed to pool the prevalence of medication errors, the proportion of patients experiencing these errors, and the error severity levels. Heterogeneity among studies was assessed using the I 2 statistic and Cochran's Q test., Results: Twenty-four studies met the inclusion criteria. The meta-analysis gave a pooled prevalence of medication errors in emergency departments of 22.6% (95% Confidence Interval [CI] 19.2-25.9%, I 2  = 99.9%, p < 0.001). The estimated proportion of patients experiencing medication errors was 36.3% (95% CI 28.3-44.3%, I 2  = 99.8%, p < 0.001). Of these errors, 42.6% (95% CI 5.0-80.1%) were potentially harmful but not life-threatening, while no-harm errors accounted for 57.3% (95% CI 14.1-100.0%)., Conclusion: The prevalence of medication errors, particularly those potentially harmful, underscores potential safety issues in emergency departments. It is imperative to develop and implement effective interventions aimed at reducing medication errors and enhancing patient safety in this setting., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

In this study, we demonstrate the influence of crystallinity and morphology on the analytical performance of various Cu 2 MoS 4 (CMS) nanocatalysts-based electrochemical sensors for the high-efficiency detection of Ofloxacin (OFX) antibiotic. The electrochemical kinetics parameters including peak current response (Δ Ip ), peak-to-peak separation (Δ Ep ), electrochemically active surface area (ECSA), electron-transfer resistance (R ct ), were obtained through the electrochemical analyses, which indicate the single-crystalline nature of CMS nanomaterials (NMs) is beneficial for enhanced electron-transfer kinetics. The morphological features and the electrochemical results for OFX detection substantiate that by tuning the tube-like to plate-like structures of the CMS NMs, it might noticeably enhance multiple adsorption sites and more intrinsic active catalytic sites due to the diffusion of analytes into the interstitial spaces between CMS nanoplates. As results, highly single-crystalline and plate-shaped morphology structures of CMS NMs would significantly enhance the electrocatalytic OFX oxidation in terms of onset potential (E onset ), Tafel slope, catalytic rate constant (k cat ), and adsorption capacity (Γ). The CMS NMs-based electrochemical sensing platform showed excellent analytical performance toward the OFX detection with two ultra-wide linear detection concentration ranges from 0.25-100 and 100-1000 μM, a low detection limit of 0.058 μM, and an excellent electrochemical sensitivity (0.743 μA μM -1  cm -2 )., (© 2024 Wiley-VCH GmbH.)

Background: Pediatric melanoma presents with distinct clinical features compared to adult disease., Objective: Characterize risk factors and negative outcomes in pediatric melanoma., Methods: Multicenter retrospective study of patients under 20 years diagnosed with melanoma between January 1, 1995 and June 30, 2015 from 11 academic medical centers., Results: Melanoma was diagnosed in 317 patients, 73% of whom were diagnosed in adolescence (age ≥11). Spitzoid (31%) and superficial spreading (26%) subtypes were most common and 11% of cases arose from congenital nevi. Sentinel lymph node biopsy was performed in 68% of cases and positive in 46%. Fatality was observed in 7% of cases. Adolescent patients with melanoma were more likely to have family history of melanoma (P = .046) compared to controls., Limitations: Retrospective nature, cohort size, control selection, and potential referral bias., Conclusion: Pediatric melanoma has diverse clinical presentations. Better understanding of these cases and outcomes may facilitate improved risk stratification of pediatric melanoma., Competing Interests: Conflicts of interest SH reports honorarium from Elsevier and past consulting for Novan Pharmaceuticals., (Copyright © 2024. Published by Elsevier Inc.)

The adsorption and degradation capacities of dichlorodiphenyltrichloroethane (DDT) on a photocatalyst composed of TiO 2 supported on the mesoporous material MCM-41 (TiO 2 /MCM-41) were investigated using density functional theory and real-time density functional theory methods. The van der Waals interactions within the PBE functional were adjusted by using the Grimme approach. The adsorption of DDT was evaluated through analyses involving adsorption energy, Hirshfeld atomic charges, Wiberg bond orders, molecular electrostatic potential, noncovalent interaction analysis, and bond path analysis. The findings reveal that DDT undergoes physical adsorption on pristine MCM-41 or MCM-41 modified with Al or Fe due to the very small bond order (only about 0.15-0.18) as well as the change in total charge of DDT after adsorption is close to 0. However, it chemically adsorbs onto the TiO 2 /MCM-41 composite through the formation of Ti···Cl coordination bonds because the maximum bond order is very large, about 1.0 (it can be considered as a single bond). The adsorption process is significantly influenced by van der Waals interactions (accounting for approximately 30-40% of the interaction energy), hydrogen bonding, and halogen bonding. MCM-41 is demonstrated to concurrently function as a support for the TiO 2 photocatalyst, creating a synergistic effect that enhances the photocatalytic activity of TiO 2 . Based on the computational results, a novel photocatalytic mechanism for the degradation of DDT on the TiO 2 /MCM-41 catalyst system was proposed., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: The booster vaccine is essential for maintaining the antibody against the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) virus. This study sought to evaluate the antibody response after booster coronavirus disease 2019 (COVID-19) vaccines and compare the immunogenic by different vaccine combination strategies., Methods: A cross-sectional study in Hanoi, Vietnam was conducted on 679 adult participants who received two doses of vaccines with any combination of AstraZeneca, Pfizer, and Moderna during the COVID-19 vaccination campaign in 2021. The SARS-CoV-2 S1/S2 Immunoglobulin G (IgG) antibody concentrations were measured by the LIAISON SARS-CoV-2 S1/S2 IgG and presented as arbitrary units., Results: We found that the median (interquartile range (IQR)) of IgG level among those who completed two doses of Moderna and Pfizer was 484.55 (284.80) AU/mL and 349.00 (362.50) AU/mL, respectively. Meanwhile, the counterpart of AstraZeneca was 110.00 (128.10) AU/mL. Mixing two doses of AstraZeneca-Pfizer has higher odds of having high IgG level than two doses of Pfizer (Odds Ratios (OR) = 2.94, 95% Confidence Intervals (CI): 1.57-5.51), AstraZeneca (OR = 28.50, 95% CI: 15.00-54.14)., Conclusions: We found that the matching two doses of mRNA vaccines are more immunogenic as compared to the DNA vector vaccines. Furthermore, mixing AstraZeneca-Pfizer has higher antibody quantities as compared to matching vaccines, while lower the rate of advert events.

Introduction: Brain cancer is the leading cause of cancer-related deaths in children and the majority of childhood brain tumors are diagnosed without determination of their underlying etiology. Little is known about risk factors for childhood brain tumors in Vietnam. The objective of this case-control study was to identify maternal and perinatal factors associated with brain tumors occurring in young Vietnamese children and adolescents., Methods: We conducted a hospital-based case-control study at Viet Duc University Hospital in Hanoi, Vietnam. Cases consisted of children with brain tumors aged 0-14 years old admitted to the hospital from January 2020 to July 2022 while the controls were age and sex-matched hospitalized children diagnosed with head trauma. Perinatal characteristics were abstracted from hospital medical records and maternal medical, behavioral, and sociodemographic factors were collected through in-person interviews. Conditional logistic regression models were used to examine maternal and perinatal factors associated with childhood brain tumors., Results: The study sample included 220 children (110 cases and 110 controls) whose average age was 8.9 years and 41.8% were girls. Children born to mothers aged greater than 30 years at the time of the child's birth had a higher risk of childhood brain tumors compared to those born to mothers aged from 18 to 30 years old (OR = 2.55; 95% CI: 1.13-5.75). Additionally low maternal body mass index prior to the current pregnancy of <18.5 kg/m 2 significantly increased the odds of having a child with a brain tumor in relation to normal maternal body mass index from 18.5-22.9 kg/m 2 (OR = 3.19; 95% CI: 1.36 - 7.50)., Conclusion: Advanced maternal age and being markedly underweight were associated with an increased odds of having a child with a brain tumor. A population-based study with larger sample size is needed to confirm and extend the present findings., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study assessed the methylene blue adsorption using natural and modified mussel shell powders in the aqueous solution. The mussel shell samples were processed in a NaClO solution then modified with sodium dodecyl sulfate and ethylenediaminetetraacetic acid. The characteristics of mussel shell samples before and after modification were demonstrated using infared spectroscopy, thermogravimetric analysis, scanning electron microscopy, nitrogen adsorption/desorption, energy dispersive X-ray, water contact angle, and dynamic light scattering methods. Some factors such as the pH of the medium, adsorption temperature, and adsorption time had a significant effect on the methylene blue adsorption of mussel shell samples. The adsorption isotherm models and kinetics of methylene blue adsorption by mussel shell samples were also studied. A quadratic regression equation was selected with experimental planning following the Box-Behnken model combined with Design Expert 11.1.0.1 software to optimize the methylene blue adsorption process by mussel shell samples. These results open a promising direction for using naturally derived materials to remove organic pollutants from contaminated water., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Breast cancer remains one of the major cancers worldwide. In Asia, breast cancer is leading both incidence and mortality rates. Health-related quality of life (HRQoL) studies play an important role in clinical treatment. This systematic review aimed to summarize the evidence of HRQoL and associated factors among patients with breast cancer in low-and-middle-income countries (LMICs) in Asia., Method: Performed according to PRISMA guidelines for systematic review, the studies were searched from three databases (PubMed, Cochrane, Scopus) up to November 2020. The studies which met the predefined eligibility criteria were selected, extracted, and assessed the quality according to the Newcastle-Ottawa Scale (NOS) tool., Results and Discussion: A total of 2,620 studies were searched on the three databases, of which 28 met the selection criteria, then, were included in the systematic review. The Global Health Status (GHS) score of breast cancer patients based on the EORTC QLQ-C30 questionnaire ranged from 56.32 ± 25.42 to 72.48 ± 15.68. The overall HRQoL scores using the FACT-G and FACT-B instruments ranged from 60.78 ± 13.27 to 82.23 ± 12.55 and from 70.29 ± 13.33 to 108.48 ± 19.82, respectively. Factors affecting HRQoL of patients with breast cancer included age, education level, income, marital status, lifestyle, tumor stage, method, and treatment duration. Patient's income showed a consistent effect on HRQoL while the remaining factors reported inconsistent findings across the studies. In conclusion, the HRQoL of breast cancer patients in LMICs in Asia was low and affected by several sociodemographic factors which should be studied more in future research., 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., (© 2023 Ngo, Nguyen, Nguyen, Vo, Phung, Pham, Vo, Dang, Nguyen Le Bao and Duong.)

Introduction: Autoimmune bullous dermatoses (ABD) represent a heterogeneous group of blistering disorders that may be debilitating with high morbidity. Clinical, histological, and direct immunofluorescence (DIF) studies are essential in establishing an accurate diagnosis of ABD, which is essential for its clinical management. Our study objective was to perform a systematic evaluation of ABD cases in a patient population at an academic medical center in Ho Chi Minh City, Vietnam, and determine the degree of concordance of clinical, histological, and DIF findings in ABD. Methodology: A systematic retrospective cross-sectional study was performed on 92 patients diagnosed with ABD by clinical, histological, and DIF studies at the University of Medicine and Pharmacy in Ho Chi Minh City, Vietnam, between September 2019 and September 2021. The clinical histories, H and E stained tissue sections, and DIF stains were evaluated by pathologists at the University of Medicine and Pharmacy. Results: ABD was evaluated as a whole and subdivided into an intraepidermal blister subgroup and a subepidermal blister subgroup. The analysis of paired diagnostic methods (clinical, histological, and DIF) for concordance with the final diagnosis was performed and showed that there were no statistically significant differences between the paired methods (McNemar’s test, p > 0.05). There was moderate concordance between the clinical, histological, and DIF diagnoses among all ABD cases (Brennan-Prediger coefficient Kappa test, κBP = 0.522, CI = 0.95). In the intraepidermal blister subgroup, the diagnostic accuracies of the histology and DIF stains were comparable to each other, and both were more accurate than a clinical diagnosis alone. In the subepidermal blister subgroup, there was no statistically significant difference in each pair of the three diagnostic methods (clinical, histological, and DIF) (McNemar’s test, p > 0.05). The concordance between the clinical, histological, and DIF diagnoses was high for the intraepidermal blister subgroup (Kappa test, κBP = 0.758, CI = 0.95). However, the concordance between the clinical, histological, and DIF diagnoses was slight for the subepidermal blister subgroup (Kappa test, κBP = 0.171, CI = 0.95). Conclusion: Histological evaluation is highly accurate in the diagnosis of the intraepidermal blister subgroup, but it is not as accurate in the diagnosis of the subepidermal blister subgroup in the Vietnamese patient cohort in which clinical, histological, and DIF studies were performed. DIF stains are a crucial diagnostic tool for ABD in this patient population.

Vascular tumors are neoplasms of endothelial cell origin. These tumors comprise a broad and complex group of vascular anomalies. Diagnostic classification of these lesions is based on their unique clinical, radiologic imaging, histopathologic, and molecular characteristics. This article follows the published classification of the International Society for the Study of Vascular Anomalies. It describes characteristic histopathologic findings in vascular tumors and information on known genetic causes., Competing Interests: Disclosure The author has no conflict of interest to disclose pertaining to this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Vascular malformations are developmental disorders involving the blood and lymphatic vasculature. The study of vascular malformations is a complex and rapidly evolving field with new understanding and insights into the clinical, histopathology, and molecular basis of these lesions. Diagnostic classification of vascular malformations is based on their unique clinical, radiologic imaging, histologic, and molecular characteristics. This article follows the published classification of the International Society for the Study of Vascular Anomalies. It describes characteristic histopathologic findings in tissues of vascular malformations and information on known genetic causes., Competing Interests: Disclosure The author has no conflict of interest to disclose pertaining to this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: This study investigated the efficacy and safety of pharmacologic interventions to prevent vertical transmission of the hepatitis B virus., Data Sources: Medline, Cochrane, and Scopus databases were searched up to October 28, 2020., Study Eligibility Criteria: All randomized controlled trials reporting vertical hepatitis B virus transmission with pharmacologic intervention were included., Methods: Risk of bias was assessed using the Cochrane Risk-of-Bias tool, version 2. Treatment efficacy was estimated using stratified network meta-analysis on the basis of maternal hepatitis B envelope antigen status., Results: Nineteen studies were included for mothers positive for hepatitis B surface and envelope antigens. Pooling indicated that a combination of hepatitis B vaccination and hepatitis B immunoglobulin in infants significantly reduced transmission risk compared with vaccination alone, with a risk ratio of 0.52 (95% confidence interval; 0.30-0.91). Only the addition of maternal tenofovir disoproxil fumarate, but not telbivudine, lamivudine, or maternal hepatitis B immunoglobulin further reduced transmission risk compared with a combination of hepatitis B vaccination and hepatitis B immunoglobulin in infants, with a pooled risk ratio of 0.10 (0.03-0.35). Twelve studies conducted in mothers with hepatitis B surface antigen positivity and mixed, unknown, or negative hepatitis B envelope antigen status provided limited evidence to suggest that maternal hepatitis B immunoglobulin combined with hepatitis B vaccination and immunoglobulin in infants was the likely best treatment, but this failed to reach statistical significance compared with a combination of hepatitis B vaccination and immunoglobulin in infants. Similarly, infant hepatitis B immunoglobulin, added to vaccination, likely provides additional benefit but failed to reach statistical significance., Conclusion: A combination of hepatitis B vaccination and immunoglobulin in infants is the cornerstone for prevention of vertical transmission for mothers positive for both hepatitis B surface and envelope antigens. The addition of maternal tenofovir to this infant combination regimen was considered the likely most effective treatment. For infants of mothers with hepatitis B surface antigen positivity and mixed, unknown, or negative hepatitis B envelop antigen status, no additional agents provided further benefit beyond hepatitis B vaccination alone., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

One in 10 infants are born with a vascular birthmark each year. Some vascular birthmarks, such as infantile hemangiomas, are common, while vascular malformations, such as capillary, lymphatic, venous, and arteriovenous malformations, are less so. Diagnosing uncommon vascular birthmarks can be challenging, given the phenotypic heterogeneity and overlap among these lesions. Both sporadic and germline variants have been detected in various genes associated with vascular birthmarks. Identification of these genetic variants offers insight into both diagnosis and underlying molecular pathways and can be fundamental in the discovery of novel therapeutic approaches. The PIK3/AKT/mTOR and RAS/MEK/ERK signaling pathways, which mediate cell growth and angiogenesis, are activated secondary to genetic variations in vascular malformations. Somatic variants in TEK (TIE2) and PIK3CA cause venous malformations. Variants in PIK3CA also cause lymphatic malformations as well as a number of overgrowth syndromes associated with vascular anomalies. Variants in GNAQ and GNA11 have been identified in both so-called "congenital" hemangiomas and capillary malformations. RASA1 and EPHB4 variants are associated with capillary malformation-arteriovenous malformation syndrome. This review discusses the genetics of vascular birthmarks, including the various phenotypes, genetic variants, pathogenesis, associated syndromes, and new diagnostic techniques., Competing Interests: Conflict of interest The authors have no potential conflicts of interest to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The model of trauma in Vietnam has changed significantly over the last decade and requires reforming medical education to deal with new circumstances. Our aim is to evaluate this transition regarding the new target by analyzing trauma and the medical training system as a whole., Objective: This study aimed to establish if medical training in the developing country of Vietnam has adapted to the new disease pattern of road trauma emerging in its economy., Methods: A review was performed of Vietnamese medical school, Ministry of Health, and Ministry of Education and Training literature on trauma education. The review process and final review paper were prepared following the guidelines on scoping reviews and using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flowchart., Results: The current trauma training at the undergraduate level is minimal and involves less than 5% of the total credit. At the postgraduate level, only the specialties of surgery and anesthesia have a significant and increasing trauma training component ranging from 8% to 22% in the content. Trauma training, which focuses on practical skills, accounts for 31% and 32% of the training time of orientation courses for young doctors in "basic surgery" and "basic anesthesia," respectively. Other relevant short course trainings, such as continuing medical education, in trauma are available, but they vary in topics, facilitators, participants, and formats., Conclusions: Medical training in Vietnam has not adapted to the new emerging disease pattern of road trauma. In the interim, the implementation of short courses, such as basic trauma life support and primary trauma care, can be considered as an appropriate method to compensate for the insufficient competency-related trauma care among health care workers while waiting for the effectiveness of medical training reformation., (©Ba Tuan Nguyen, Toi Lam Phung, Thi Hong Hanh Khuc, Van Anh Thi Nguyen, Christopher Leigh Blizzard, Andrew Palmer, Huu Tu Nguyen, Thang Cong Quyet, Mark Nelson. Originally published in JMIR Medical Education (https://mededu.jmir.org), 24.01.2022.)

&lt;b&gt;Background and Objective:&lt;/b&gt; Basil (&lt;i&gt;Ocimum basilicum&lt;/i&gt; L.), an aromatic herb, is considered one of the most important crops with essential oils as well as other bioactive compounds. Basil leaves have tremendous pharmaceutical benefits and are used for foods. Slow-release fertilizers have been developed to optimize the fertilization of crops. This work aims to discover the effect of NPK Slow-Release Fertilizer Coated by Starch (NPK-SRFS) at different rates on growth, yield and essential oil components of basil grown on the field in Northern Vietnam. &lt;b&gt;Materials and Methods:&lt;/b&gt; Basil seedlings, sown from seeds, were used as plant materials. NPK-SRFS was stocked in the Faculty of Chemistry, Hanoi Pedagogical University 2. The experiments were designed in a fully randomized block model, consisting of four treatments with different rates of NPK-SRFS. Each treatment had three replicates with an area of 8 m&lt;sup&gt;2&lt;/sup&gt;. Duncan's Multiple Range Test was being used for statistical analysis (p = 0.05). &lt;b&gt;Results:&lt;/b&gt; All 3 NPK-SRFS treatments significantly increased the number of buds and leaves per plant compared to the control. However, NPK-SRFS at different rates affected diversely plant height and leaf area of the basil. F5.0 and F10 treatments accelerated chlorophyll content as well as Fv/Fm value in comparison with none NPK-SRFS treatment. The application of NPK-SRFS at different rates caused slightly different changes in basil essential oil composition, especially the content of Methyl Chavicol, the most abundant oxygenated monoterpene and α-trans-Bergamotene, the most abundant sesquiterpene hydrocarbon. &lt;b&gt;Conclusion:&lt;/b&gt; The present study provides further insight into the influence of NPK-SRFS on the growth, yield and essential oil components of basil.

Introduction: Coronavirus disease 2019 (COVID-19) has significantly affected health care workers (HCWs), including their mental health. However, there has been limited evidence on this topic in the Vietnamese context. Therefore, this study aimed to explore COVID-19-related, psychological stress risk factors among HCWs, their concerns and demands for mental health support during the pandemic period. Methods: We employed a cross-sectional study design with convenience sampling. An online, self-administered questionnaire was used and distributed through social media among medical and non-medical HCWs from April 22 to May 12, 2020. HCWs were categorized either as frontline or non-frontline. We measured the prevalence of psychological stress using the Impact of Event Scale-Revised (IES-R) instrument. Multivariate binary logistic regression analysis was performed to identify risk factors associated with psychological stress among HCWs. Results: Among the 774 enrolled participants, 761 (98.3%) eligible subjects were included in the analysis. Most respondents were females (58.2%), between 31 and 40 years of age (37.1%), lived in areas where confirmed COVID-19 cases had been reported (61.9%), medical HCWs (59.9%) and practiced being at the frontline (46.3%). The prevalence of stress was 34.3%. We identified significant risk factors such as being frontline HCWs (odds ratio [OR] = 1.77 [95% confidence interval [CI]: 1.17-2.67]), perceiving worse well-being as compared to those before the COVID-19 outbreak [OR = 4.06 (95% CI: 2.15-7.67)], and experiencing chronic diseases [OR = 1.67 (95% CI: (1.01-2.77)]. Majority (73.9%) were concerned about testing positive for COVID-19 and exposing the infection to their families. Web-based psychological interventions that could provide knowledge on managing mental distress and consulting services were highly demanded among HCWs. Conclusion: The prevalence of psychological stress among HCWs in Vietnam during the COVID-19 pandemic was high. There were also significant risk factors associated with it. Psychological interventions involving web-based consulting services are highly recommended to provide mental health support among HCWs., 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 © 2021 Nguyen, Nguyen, Pham, Duong, Gloria, Vo, Vo and Phung.)

Competing Interests: Competing interest statement: C.L.S. is employed through Torreyana Corp, San Diego, CA; Blackhawk Genomics, Concord, CA; and Advagenix, Rockville, MD. Volunteer activities of C.L.S. include those for College of American Pathologists, Northfield, IL, and Clinical Laboratory Standards Institute, Wayne, PA. T.J.O. is a Member, Scientific Advisory Committee, MioDx and Integrated Nano-Technologies. A.W.I.L.’s laboratory receives sponsorships from AstraZeneca (HK) Ltd. and MSD (HK) Ltd. for providing selected companion diagnostic tests free to public patients. N.C. is an employee at Quest Diagnostics, Inc. F.A.M. is an employee and stock option holder at Castle Biosciences, Inc. A.B.C. is paid teaching faculty for the American Medical Informatics Association Clinical Informatics Board Review Course and receives small honoraria as well as travel reimbursement to speak at multiple scientific and professional medical society meetings. T.L.P. has been consulted (compensated) for Bio-Rad, Inc. and is Director of Pathology Strategies for the Sturge Weber Foundation (compensated). H.E.W. has employment through Viapath, a majority National Health Service-owned independent pathology service provider; has been a paid faculty member at Kingston University, accepted paid accommodation and subsistence as an invited speaker to Cytocell User Group meeting for the United Kingdom and Ireland, and accepted paid event registration as an invited speaker to Digital Pathology/Global Engage meeting. H.E.W.’s laboratory received scholarship funds from The International Council for Standardization in Haematology for providing JAK2 testing. The other authors (K.F., E.A.B., P.M., N.R.P., K.P.P., B.S., M.S., M.L.G., S.M.M., H.F., and S.O.) do not have any affiliations, memberships, funding, or financial holdings that might be perceived as affecting the objectivity of this article.

Background/objectives: Though maculopapular cutaneous mastocytosis is the most common form of pediatric mastocytosis, it remains unclear which patients will experience severe symptoms. We sought to better define the presentation and the cutaneous and systemic signs and symptoms in patients with maculopapular cutaneous mastocytosis., Methods: We analyzed retrospective data on 227 patients diagnosed with maculopapular cutaneous mastocytosis prior to age 15 years from five US clinical sites. We collected data on signs, symptoms, age of onset, and laboratory testing., Results: Median age of onset of maculopapular cutaneous mastocytosis was 3 months, with 94% of patients presenting prior to age 2 (range 0-15 years). Patients presenting before age 2 had significantly lower serum tryptase level (P = .019). Greater number of skin lesions (P = .006), number of reported skin signs and symptoms (P < .001), and higher tryptase levels (P < .001) were associated with more systemic symptoms., Conclusion: Children with maculopapular cutaneous mastocytosis, who have greater skin involvement, higher serum tryptase level, and more skin signs and symptoms, are more likely to have systemic symptoms., (© 2020 Wiley Periodicals LLC.)

Introduction: In order to standardize and expedite molecular biomarker testing, we implemented reflex ordered testing of targeted gene alterations in newly diagnosed lung adenocarcinomas within our hospital system., Patients and Methods: Reflex ordered testing of specific molecular biomarkers at the time of pathologic diagnosis of lung adenocarcinoma was approved and adopted system-wide in our hospital during 2017. Through institutional review board approval, we retrospectively looked at cohort of patients whose specimens received a diagnosis of lung adenocarcinoma, with molecular biomarker testing performed at Houston Methodist Hospital between 2016 and 2018. We compared average turnaround time (TAT) from 2016 (prior to reflex ordered testing) to 2017 and 2018 (post reflex ordered testing)., Results: Standard molecular testing performed on 39 patients in 2016 had an average TAT of 52.6 days, whereas reflex ordered molecular testing in 2017 yielded an average TAT of 26.5 days (n = 127) and 15.6 days in 2018 (n = 54). The average TAT for reporting of molecular results significantly decreased by 37 days (P = .0002) within our hospital system post adoption of reflex ordered testing for lung adenocarcinoma. Reflex ordered testing also resulted in a higher variant detection rate than standard molecular biomarker ordering practices (48.8% vs. 25.6%; P < .05). Overall, the frequencies and types of variants identified among our cohort were similar to previous reports., Conclusions: Reflex ordered testing of molecular biomarkers in lung adenocarcinoma led to significantly decreased TAT within our hospital system and higher detection rates of targeted gene alterations., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To identify risk factors associated with nonmelanoma skin cancer (NMSC) occurrence and survival in children., Study Design: This was a multicenter, retrospective, case-control study of patients <20 years of age diagnosed with NMSC between 1995 and 2015 from 11 academic medical centers. The primary outcome measure was frequency of cases and controls with predisposing genetic conditions and/or iatrogenic exposures, including chemotherapy, radiation, systemic immunosuppression, and voriconazole., Results: Of the 124 children with NMSC (40 with basal cell carcinoma, 90 with squamous cell carcinoma), 70% had at least 1 identifiable risk factor. Forty-four percent of the cases had a predisposing genetic condition or skin lesion, and 29% had 1 or more iatrogenic exposures of prolonged immunosuppression, radiation therapy, chemotherapy, and/or voriconazole use. Prolonged immunosuppression and voriconazole use were associated with squamous cell carcinoma occurrence (cases vs controls; 30% vs 0%, P = .0002, and 15% vs 0%, P = .03, respectively), and radiation therapy and chemotherapy were associated with basal cell carcinoma occurrence (both 20% vs 1%, P < .0001). Forty-eight percent of initial skin cancers had been present for >12 months prior to diagnosis and 49% of patients were diagnosed with ≥2 skin cancers. At last follow-up, 5% (6 of 124) of patients with NMSC died. Voriconazole exposure was noted in 7 cases and associated with worse 3-year overall survival (P = .001)., Conclusions: NMSC in children and young adults is often associated with a predisposing condition or iatrogenic exposure. High-risk patients should be identified early to provide appropriate counseling and management., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To define the types of hepatic hemangiomas using the updated International Society for the Study of Vascular Anomalies classification and to create a set of guidelines for their diagnostic evaluation and monitoring., Study Design: We used a rigorous, transparent consensus protocol defined by an approved methodology, with input from multiple pediatric experts in vascular anomalies from hematology-oncology, surgery, pathology, radiology, and gastroenterology., Results: In the first section, we define the subtypes of hepatic hemangiomas based on the clinical course, histology, and radiologic characteristics. We recommend against using the term "hemangioma" for any vascular malformations affecting the liver or any hypervascular tumors that are not characterized by the approved definitions. We recommend against using the term "hemangioendothelioma" for infantile or congenital hemangioma. The following 2 sections dedicated to infantile hepatic hemangioma and to congenital hepatic hemangioma individually describe these subtypes in further detail, including complications to be considered during monitoring and respectively recommended screening evaluations., Conclusions: Although institutional variations may exist for specific clinical details, a clear understanding of the diagnosis of hepatic hemangiomas affecting children and the possible complications that require screening during the monitoring period should be standard. As children with hepatic hemangiomas are managed by different medical and surgical specialties, we offer an expert opinion multidisciplinary consensus based on current literature and on data extracted from the liver hemangioma registry., (Copyright © 2018 Elsevier Inc. All rights reserved.)

To investigate whether endothelial Akt1 activation is sufficient to induce vascular tumor formation in the skin, we have developed a skin graft model in which a skin fragment from transgenic donor mice with inducible and endothelial cell-specific overexpression of activated Akt1 (myrAkt1) is grafted into the skin of wild type recipient mice. The donor skin successfully engrafts after two weeks and, more importantly, vascular tumor develops at the site of transgenic skin graft when myrAkt1 expression is turned on. This skin graft model is a novel approach to investigate the biological impact of a key signal transduction molecule in a temporal, localized and organ-specific manner., (Copyright © 2017 The Authors; exclusive licensee Bio-protocol LLC.)

Blockade of angiogenesis can retard tumour growth, but may also paradoxically increase metastasis. This paradox may be resolved by vessel normalization, which involves increased pericyte coverage, improved tumour vessel perfusion, reduced vascular permeability, and consequently mitigated hypoxia. Although these processes alter tumour progression, their regulation is poorly understood. Here we show that type 1 T helper (T H 1) cells play a crucial role in vessel normalization. Bioinformatic analyses revealed that gene expression features related to vessel normalization correlate with immunostimulatory pathways, especially T lymphocyte infiltration or activity. To delineate the causal relationship, we used various mouse models with vessel normalization or T lymphocyte deficiencies. Although disruption of vessel normalization reduced T lymphocyte infiltration as expected, reciprocal depletion or inactivation of CD4 + T lymphocytes decreased vessel normalization, indicating a mutually regulatory loop. In addition, activation of CD4 + T lymphocytes by immune checkpoint blockade increased vessel normalization. T H 1 cells that secrete interferon-γ are a major population of cells associated with vessel normalization. Patient-derived xenograft tumours growing in immunodeficient mice exhibited enhanced hypoxia compared to the original tumours in immunocompetent humans, and hypoxia was reduced by adoptive T H 1 transfer. Our findings elucidate an unexpected role of T H 1 cells in vasculature and immune reprogramming. T H 1 cells may be a marker and a determinant of both immune checkpoint blockade and anti-angiogenesis efficacy.

Cutis laxa is characterized by dramatic wrinkling of skin that is lacking in elasticity due to inherent defects in dermal elastic fibers. Cutis laxa can be caused by genetic and metabolic disorders. It can also be acquired, possibly resulting from inflammatory processes with destruction of elastic fibers. This report describes a 26-year old woman who developed acquired cutis laxa and cutaneous mastocytosis leading to premature aging. She represents a unique co-occurrence of these two separate disease entities. To our knowledge, there has been only one published case report of acquired cutis laxa occurring in association with urticaria pigmentosa in a 4-year old girl. Our case would be a second case that exhibits the coexistence of these two disorders in an adult female.

Radiation injury to the skin is a major source of dysfunction, disfigurement, and complications for thousands of patients undergoing adjunctive treatment for internal cancers. Despite the great potential for affecting quality of life, radiation injury has received little attention from dermatologists and is primarily being managed by radiation oncologists. During our volunteer work in Vietnam, we encountered numerous children with significant scarring and depigmentation of skin from the outdated use of radioactive phosphorus P32 in the treatment of hemangiomas. This dangerous practice has left thousands of children with significant fibrosis and disfigurement. Currently, there is no treatment for radiation dermatitis. Here, we report a case series using the combination of laser treatment, including pulsed-dye laser, fractional CO2 laser, and epidermal grafting to improve the appearance and function of the radiation scars in these young patients. We hope that by improving the appearance and function of these scars, we can improve the quality of life for these young patients and potentially open up a new avenue of treatment for cancer patients affected with chronic radiation dermatitis, potentially improving their range of motion, cosmesis, and reducing their risk of secondary skin malignancies., (©2015 Frontline Medical Communications.)

Vascular tumors are endothelial cell neoplasms whose mechanisms of tumorigenesis are poorly understood. Moreover, current therapies, particularly those for malignant lesions, have little beneficial effect on clinical outcomes. In this study, we show that endothelial activation of the Akt1 kinase is sufficient to drive de novo tumor formation. Mechanistic investigations uncovered opposing functions for different Akt isoforms in this regulation, where Akt1 promotes and Akt3 inhibits vascular tumor growth. Akt3 exerted negative effects on tumor endothelial cell growth and migration by inhibiting activation of the translation regulatory kinase S6-Kinase (S6K) through modulation of Rictor expression. S6K in turn acted through a negative feedback loop to restrain Akt3 expression. Conversely, S6K signaling was increased in vascular tumor cells where Akt3 was silenced, and the growth of these tumor cells was inhibited by a novel S6K inhibitor. Overall, our findings offer a preclinical proof of concept for the therapeutic utility of treating vascular tumors, such as angiosarcomas, with S6K inhibitors., (©2014 American Association for Cancer Research.)

Vascular tumors are endothelial cell neoplasms whose cellular and molecular mechanisms, leading to tumor formation, are poorly understood, and current therapies have limited efficacy with significant side effects. We have investigated mechanistic (mammalian) target of rapamycin (mTOR) signaling in benign and malignant vascular tumors, and the effects of mTOR kinase inhibitor as a potential therapy for these lesions. Human vascular tumors (infantile hemangioma and angiosarcoma) were analyzed by immunohistochemical stains and western blot for the phosphorylation of p70 S6-kinase (S6K) and S6 ribosomal protein (S6), which are activated downstream of mTOR complex-1 (mTORC1). To assess the function of S6K, tumor cells with genetic knockdown of S6K were analyzed for cell proliferation and migration. The effects of topical rapamycin, an mTOR inhibitor, on mTORC1 and mTOR complex-2 (mTORC2) activities, as well as on tumor growth and migration, were determined. Vascular tumors showed increased activation of S6K and S6. Genetic knockdown of S6K resulted in reduced tumor cell proliferation and migration. Rapamycin fully inhibited mTORC1 and partially inhibited mTORC2 activities, including the phosphorylation of Akt (serine 473) and PKCα, in vascular tumor cells. Rapamycin significantly reduced vascular tumor growth in vitro and in vivo. As a potential localized therapy for cutaneous vascular tumors, topically applied rapamycin effectively reduced tumor growth with limited systemic drug absorption. These findings reveal the importance of mTOR signaling pathways in benign and malignant vascular tumors. The mTOR pathway is an important therapeutic target in vascular tumors, and topical mTOR inhibitors may provide an alternative and well-tolerated therapy for the treatment of cutaneous vascular lesions.

Tumors are composed of cancer cells but also a larger number of diverse stromal cells in the tumor microenvironment. Stromal cells provide essential supports to tumor pathophysiology but the distinct characteristics of their signaling networks are not usually considered in developing drugs to target tumors. This oversight potentially confounds proof-of-concept studies and increases drug development risks. Here, we show in established murine and human models of breast cancer how differential regulation of Akt by the small GTPase RhoB in cancer cells or stromal endothelial cells determines their dormancy versus outgrowth when angiogenesis becomes critical. In cancer cells in vitro or in vivo, RhoB functions as a tumor suppressor that restricts EGF receptor (EGFR) cell surface occupancy as well as Akt signaling. However, after activation of the angiogenic switch, RhoB functions as a tumor promoter by sustaining endothelial Akt signaling, growth, and survival of stromal endothelial cells that mediate tumor neoangiogenesis. Altogether, the positive impact of RhoB on angiogenesis and progression supercedes its negative impact in cancer cells themselves. Our findings elucidate the dominant positive role of RhoB in cancer. More generally, they illustrate how differential gene function effects on signaling pathways in the tumor stromal component can complicate the challenge of developing therapeutics to target cancer pathophysiology.

Cutaneous vascular anomalies are congenital disorders of abnormal vascular development and growth. Infantile hemangioma is a common type of vascular anomalies characterized by the abnormal growth of blood vessels in the early proliferative phase, followed by the gradual spontaneous regression of the lesion in the involuting phase. Over the past decade, significant advances have been made in our understanding of the cellular and molecular mechanisms that control the development, growth, and regression of infantile hemangioma. In this article, we present a comprehensive review of the current knowledge of the pathogenesis of hemangioma as well as promising research horizons and implications for new therapeutic advances., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Basal cell carcinoma (BCC) is a common skin cancer for which the treatment and recurrence risk correlate with the histologic subtype. Limited information is available regarding the accuracy of biopsy in diagnosing BCC subtypes., Objective: We sought to determine the correlation between BCC subtypes present in a biopsy specimen and the actual subtypes present in a tumor., Methods: In this retrospective study, skin biopsy specimens and corresponding excisions were reviewed. All histologic subtypes present in the biopsy specimen were reported and compared with the composite BCC subtype present in the biopsy specimen and excision., Results: A total of 232 biopsy specimens and corresponding wide excisions were examined. The biopsy specimen accuracy rate was 82% for punch and shave biopsy specimens. Mixed histologic subtypes were seen in 54% of the cases, half of which contained an aggressive subtype (infiltrative, morpheaform, or micronodular). There was an 18% discordance rate between the biopsy specimen subtype and the composite subtype. Importantly, 40% of these discordant cases (7% of all cases examined) had an aggressive subtype that was not sampled in the initial biopsy specimen. Furthermore, some cases were misidentified as infiltrative subtype in the biopsy specimen as a result of misinterpretation of surface ulceration and reactive stromal changes., Limitations: The limited number of punch biopsy specimens and the fact that Mohs excisions were not included are limitations., Conclusions: Punch and shave biopsy specimens provided adequate sampling for correct BCC subtyping in 82% of the cases examined. However, 18% of the biopsy specimens were misidentified, some of which missed an aggressive component. Thus, there are potential pitfalls in the identification of BCC subtypes in biopsy specimens, which may have important implications in treatment outcome., (Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Objective: Angiosarcoma (AS) is a rare understudied soft tissue sarcoma exhibiting endothelial cell differentiation. We sought to evaluate AS natural history in the largest patient cohort reported to date and further unravel commonly deregulated molecular events of potential therapeutic utility., Methods: Medical records of AS patients (n = 222) treated at our institution from 1993 to 2007 were reviewed. Univariable and multivariable analyses were used to identify independent outcome prognosticators. An AS tissue microarray (n = 68 human specimens) was constructed for immunohistochemical analysis of multiple potential drugable kinase-related molecular markers., Results: Forty-three (19.4%) metastatic AS patients and 179 patients (80.6%) with localized disease were included. Median survival of localized versus metastatic AS was 49 (range, 2-188) versus 10 (range, 1-69) months (P < 0.0001). Patients with localized AS who underwent complete surgical resection (n = 136; 76%) demonstrated significantly better outcome compared with those with unresectable tumors (n = 43; 24%; P < 0.0001). Of several factors identified on univariable analysis as significantly adverse for disease-specific survival, tumor size (>5 cm vs. < or = 5 cm, P = 0.01) and epithelioid histologic component (P = 0.008) remained significant on multivariable analysis as independent adverse prognosticators in complete resection patients. Immunohistochemistry identified significant overexpression of vascular endothelial growth factor-A and C as well as p-AKT, p-4EBP1, and eIF4E in human AS., Conclusions: AS harbors a dismal outcome and even patients with disease amenable to complete surgical resection exhibit a 5-year disease-specific survival of only 53%. There is a crucial need for better therapies. Data presented here support further study of the AKT/mTOR pathway as novel molecular targets for AS therapy.

Background and Objectives: Complete blanching of port wine stain (PWS) birthmarks after laser therapy is rarely achieved for most patients. We postulate that the low therapeutic efficacy or treatment failure is caused by regeneration and revascularization of photocoagulated blood vessels due to angiogenesis associated with the skin's normal wound healing response. Rapamycin (RPM), an antiangiogenic agent, has been demonstrated to inhibit growth of pathological blood vessels. Our objectives were to (1) investigate whether topical RPM can inhibit reperfusion of photocoagulated blood vessels in an animal model and (2) determine the effective RPM concentration required to achieve this objective., Study Design/materials and Methods: For both laser-only and combined laser and RPM treated animals, blood vessels in the dorsal window chambers implanted on golden Syrian hamsters were photocoagulated with laser pulses. Structural and flow dynamics of blood vessels were documented with color digital photography and laser speckle imaging to evaluate photocoagulation and reperfusion. For the combined treatment group, topical RPM was applied to the epidermal side of the window daily for 14 days after laser exposure., Results: In the laser-only group, 23 out of 24 photocoagulated blood vessels reperfused within 5-14 days. In the combined treatment group with different RPM formulae and concentrations, the overall reperfusion rate of 36% was much lower as compared to the laser-only group. We also found that the reperfusion rate was not linearly proportional to the RPM concentration., Conclusions: With topical RPM application, the frequency of vessel reperfusion was considerably reduced, which implies that combined light and topical antiangiogenic therapy might be a promising approach to improve the treatment efficacy of PWS birthmarks.

Objective: We evaluated the stages of VEGF-A(164) driven angiogenesis that are inhibited by therapeutic doses of rapamycin and the potential role of S6K1 in that response., Methods and Results: We assessed the effects of rapamycin on the several stages of angiogensis and lymphangiogenesis induced with an adenovirus expressing VEGF-A(164) (Ad-VEGF-A(164)) in the ears of adult nude mice. Rapamycin (0.5 mg/kg/d) effectively inhibited mTOR and downstream S6K1 signaling and partially inhibited Akt signaling, likely through effects on TORC2. The earliest stages of angiogenesis, including mother vessel formation and increased vascular permeability, were strikingly inhibited by rapamycin, as was subsequent formation of daughter glomeruloid microvasular proliferations. However, later stage formation of vascular malformations and lymphangiogenesis were unaffected. Retrovirally delivered isoforms and shRNAs demonstrated that S6K1 signaling plays an important role in early VEGF-A(164)-angiogenesis., Conclusions: Rapamycin potently inhibited early and mid stages of VEGF-A(164)-driven angiogenesis, but not late-stage angiogenesis or lymphangiogenesis. Rapamycin decreased phosphorylation of both Akt and S6, suggesting that both the TORC1 and TORC2 pathways are impacted. Inhibition of S6K1 signaling downstream of mTOR is a major component of the antiangiogenesis action of rapamycin.

Background: In addition to a complete skin examination every few months, adjuvant interferon treatment is often recommended for patients with high-risk melanomas. Therefore, dermatologists play an important role in detecting multiple primary melanomas and may be required to attempt to identify the primary melanoma in patients with metastatic disease., Observations: We describe 3 patients with a diagnosis of melanoma who were diagnosed as having a new primary cutaneous melanoma within weeks of initiating interferon treatment. All 3 melanomas were inflamed clinically, prompting excisional biopsy. Histopathologic analysis of the melanomas revealed thin (<1.0 mm Breslow thickness) invasive tumors, as well as the presence of tumor-infiltrating lymphocytes and/or regression., Conclusions: Inflamed melanocytic lesions in patients undergoing interferon treatment should be further evaluated to investigate the possibility of primary cutaneous melanomas. This observation may enable earlier detection and treatment of melanomas in patients with multiple tumors or metastatic melanoma with an unknown primary site.

Chronic activation of Akt signaling in the endothelium recapitulates the salient features of a tumor vasculature and can be inhibited by rapamycin, an inhibitor of mammalian target of rapamycin. This led to the hypothesis that the antitumor efficacy of rapamycin may be partially dependent on its ability to inhibit endothelial Akt signaling, making rapamycin an antiangiogenic agent and endothelial Akt pathway inhibitor. Dose-response studies with rapamycin showed that primary human endothelial cells and fibroblasts had a bimodal Akt response with effective reductions in phosphorylated Akt (pAkt) achieved at 10 ng/mL. In contrast, rapamycin increased pAkt levels in tumor cell lines. When tumor-bearing mice were treated with rapamycin doses comparable to those used clinically in transplant patients, we observed strong inhibition of mammary tumor growth. To test whether Akt activation in the endothelium was rate-limiting for this antitumor response, we engineered mouse mammary tumor virus-polyoma virus middle T antigen mice with endothelial cell-specific expression of constitutively activated Akt. We observed that the antitumor efficacy of rapamycin was reduced in the presence of elevated endothelial Akt activation. Just as we observed in MCF7 cells in vitro, rapamycin doses that were antiangiogenic resulted in increased pAkt levels in total mouse mammary tumor virus-polyoma virus middle T antigen tumor lysates, suggesting that tumor cells had an opposite Akt response following mammalian target of rapamycin inhibition compared with tumor endothelial cells. Together, these data support the hypothesis that endothelial Akt signaling in the tumor vasculature is an important target of the novel anticancer drug rapamycin.

Endothelial cells in growing tumors express activated Akt, which when modeled by transgenic endothelial expression of myrAkt1 was sufficient to recapitulate the abnormal structural and functional features of tumor blood vessels in nontumor tissues. Sustained endothelial Akt activation caused increased blood vessel size and generalized edema from chronic vascular permeability, while acute permeability in response to VEGF-A was unaffected. These changes were reversible, demonstrating an ongoing requirement for Akt signaling for the maintenance of these phenotypes. Furthermore, rapamycin inhibited endothelial Akt signaling, vascular changes from myrAkt1, tumor growth, and tumor vascular permeability. Akt signaling in the tumor vascular stroma was sensitive to rapamycin, suggesting that rapamycin may affect tumor growth in part by acting as a vascular Akt inhibitor.

Infantile hemangiomas are the most common benign tumor of infancy, occurring shortly after birth in 5% to 10% of white infants. Hemangiomas occur in infants of all races but are most common in those who are white. These lesions are preponderant in females compared with males at rates of 3:1 to 5:1. Many hemangiomas are discrete, well-circumscribed masses present in the head and neck. Some hemangiomas are segmental and diffuse, often involving large areas of the extremities or the head and neck. Chorionic villus sampling at 9 to 12 weeks of gestation has been associated with a 21% increased incidence of hemangiomas in infants. Most hemangiomas occur sporadically without a hereditary component. However, in a few families, hemangiomas segregate as a highly penetrant, autosomal dominant trait. Gene linkage studies of familial infantile hemangiomas show evidence of linkage to chromosome 5q31-33.

A case of beta-lactam antibiotic-induced pseudoporphyria is presented. A 24-year-old African American woman with systemic lupus erythematosus and end-stage renal disease on hemodialysis developed tense bullae on her forehead and cheeks after exposure to ampicillin-sulbactam and cefepime. Histologically, the lesions were similar to porphyria cutanea tarda, but without the associated porphyrin abnormalities. The lesions resolved spontaneously on cessation of the antibiotics.

Lipoprotein and apolipoprotein parameters were studied in the male Zucker diabetic fatty (ZDF) rat at 10 and 20 weeks of age, corresponding to hyperinsulinemic and insulinopenic type 2 diabetes mellitus, respectively. At both ages, ZDF rats had elevated serum triglycerides, free fatty acids, and corticosterone, whereas 20-week ZDF rats had reduced thyroid hormones. At 10 weeks, the hyperlipidemia was confined to elevations in pre-beta triglyceride-rich (d < 1.006 g/mL) lipoproteins. By 20 weeks, all lipoprotein density fractions were increased compared with lean rats, with substantial increases in both low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol. In ZDF rats, there was a progressive increase in apolipoprotein B (apo B) from 1.9 times control at 10 weeks to three times control at 20 weeks. The increase in apo B was accompanied by a shift of apo B, particularly B100, from very-low-density lipoprotein (VLDL) into denser lipoproteins corresponding to intermediate-density lipoproteins plus LDLs (1.006 < d < 1.063 g/mL). In Zucker and 10-week ZDF rats, in the presence of hyperinsulinemia, the increase in serum apo B was predominantly apo B48 present in VLDL. By 20 weeks, when ZDF rats are insulinopenic, the mass ratio of B48:B100 shifted from 2.7 to 0.7. The shift was associated with a decrease in hepatic-edited apo B mRNA. Apo E increased in lean rats between 10 and 20 weeks of age. Although apo E also increased in ZDF rats, the increase by 20 weeks was less than that of lean rats. The molar ratio of apo E to B in VLDL was decreased in ZDF rats. In lean rats, greater than 50% of apo E was present in HDL, in contrast to ZDF rats, where less than 20% of apo E was present in HDL. VLDL apo E shifted to denser fractions by 20 weeks of age, similar to apo B. The apo C level was more than double compared with the level in lean rats and was redistributed from the HDL fraction to lipoprotein fractions containing apo B. Both apo A-I and apo A-IV levels more than doubled between 10 and 20 weeks in ZDF rats. The ZDF rat model may be useful in comparative studies of lipoproteins during diabetic progression from hyperinsulinemia to insulinopenia.

Insulin inhibits apolipoprotein B (apoB) secretion by primary rat hepatocytes through activation of phosphoinositide 3-kinase (PI 3-K). Current studies demonstrate that the PI 3-K inhibitor wortmannin inhibits both basal and insulin-stimulated PI 3-K activities. Wortmannin and LY 294002, two structurally distinct PI 3-K inhibitors, prevent insulin-dependent inhibition of apoB secretion in a dose-dependent manner. To link PI 3-K activation to insulin action on apoB, we investigated whether insulin induced localization of activated PI 3-K to the endoplasmic reticulum (ER), where apoB biogenesis is initiated. Insulin action results in a significant redistribution of PI 3-K to a low density microsome (LDM) fraction containing apoB protein and apoB mRNA. Insulin stimulates a significant increase in PI 3-K activity associated with insulin receptor substrate-1 as well as an increase in insulin receptor substrate-1/PI 3-K mass in LDM. Subfractionation of LDM on sucrose density gradients shows that insulin significantly increases the amount of PI 3-K present in an ER fraction containing apoB. Insulin stimulates PI 3-K activity in smooth and rough microsomes isolated from rat hepatocytes, the latter of which contain rough ER as demonstrated by electron microscopy. Studies indicate that 1) PI 3-K activity is necessary for insulin-dependent inhibition of apoB secretion by rat hepatocytes; 2) insulin action leads to the activation and localization of PI 3-K in an ER fraction containing apoB; and 3) insulin stimulates PI 3-K activity in the rough ER.