Age-related EBV-associated B-cell lymphoproliferative disorders and other EBV + lymphoproliferative diseases: New insights into immune escape and immunodeficiency through staining with anti-PD-L1 antibody clone SP142.

Epstein-Barr virus (EBV) is prevalent among healthy individuals, and is implicated in numerous reactive and neoplastic processes in the immune system. The authors originally identified a series of senile or age-related EBV-associated B-cell lymphoproliferative disorders (LPD) bearing a resemblance to immunodeficiency-associated ones. These LPDs may be associated with immune senescence and are now incorporated into the revised 4th edition of 2017 WHO lymphoma classification as EBV-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS). These EBV+ B-cells often have a Hodgkin/Reed-Sternberg (HRS)-like appearance and are shared beyond the diagnostic categories of mature B-cell neoplasms, mature T-cell neoplasms, classic Hodgkin lymphoma, and immunodeficiency-associated LPD. In addition, peculiar new diseases, such as EBV+ mucocutaneous ulcer and EBV+ DLBCL affecting the young, were recognized. On the other hand, lymphoma classification is now evolving in accord with deeper understanding of the biology of programmed death ligand 1 (PD-L1). Assessing PD-L1 positivity by staining with the anti-PD-L1 monoclonal antibody SP142 provides new insight by discriminating between immune evasion and senescence or immunodeficiency. The aim of the present review is to briefly summarize the diagnostic use of immunostaining with SP142 in malignant lymphomas and/or LPDs that feature tumor and nonmalignant large B-cells harboring EBV.

Anaplastic variant of diffuse large B-cell lymphoma: Reappraisal as a nodal disease with sinusoidal involvement.

Anaplastic variant (av) of diffuse large B-cell lymphoma (DLBCL) is morphologically defined in the 2017 World Health Organization classification, but still an enigmatic disease in its clinicopathologic distinctiveness, posing the differential diagnostic problem from gray zone lymphoma (GZL) and classic Hodgkin lymphoma (cHL). Thirty-one cases previously diagnosed as avDLBCL were reassessed. Of these, 27 (87%) and 4 (13%) were node-based and extranodal diseases, respectively. They were further reclassified into nodal avDLBCL (n = 18), nodal CD30+ DLBCL with T-cell/histiocyte-rich large B-cell lymphoma-like features (CD30+ DLBCL-THRLBCL) (n = 6), GZL with features intermediate between DLBCL and cHL (n = 3) and CD30+ extranodal DLBCL, NOS (n = 4). The nodal avDLBCL cases had a sheet-like proliferation of large cells and/or Hodgkin/Reed-Sternberg (HRS)-like cells in 12 (67%) notably with a sinusoidal pattern in 16 (89%). They showed an expression of CD20 and/or CD79a in all and CD30 in 15 of 18. All of them were negative for PD-L1 on tumor cells, although HRS-like cells showed negativity or partial loss of other B-cell markers to varying degrees. The present study highlighted the distinctiveness of the nodal avDLBCL with sinusoidal pattern, but without neoplastic PD-L1 expression, which provide refined diagnostic criteria for a more precise pathologic and clinical characterization of this disease.

Optical modeling of black silicon using an effective medium/multi-layer approach.

In this work, black silicon (BSi) structures including nanocones and nanowires are modeled using effective medium theory (EMT), where each structure is assumed to be a multilayer structure of varying effective index, and its optical scattering in the infrared range is studied in terms of its total reflectance, transmittance and absorptance using the transfer matrix method (TMM). The different mechanisms of the intrinsic absorption of silicon are taken into account, which translates into proper modeling of its complex refraction index, depending on several parameters including the doping level. The model validity is studied by comparing the results with the rigorous coupled wave analysis and is found to be in good agreement. The effect of the aspect ratio, the spacing between the structure features and the structure disordered nature are all considered. Moreover, the results of the proposed model are compared with reflectance measurements of a fabricated BSi sample, in addition to other measurements reported in the literature for Silicon Nanowires (SiNWs). The TMM along with EMT proves to be a convenient method for modeling BSi due to its simple implementation and computational speed.

Grey zone lymphoma with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma: a clinicopathological study of 14 Epstein-Barr virus-positive cases.

AIMS: To investigate the clinicopathological features of Epstein-Barr virus (EBV)-positive grey zone lymphoma (GZL) with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (CHL). METHODS AND RESULTS: We investigated the clinicopathological features of 14 cases of EBV-positive GZL in Japan. The control group included 173 cases of EBV-positive CHL and 64 cases of EBV-positive DLBCL of the elderly (polymorphous type). The patients were 10 men and four women with a median age of 62 years. Twelve patients (86%) had advanced clinical stage, 11 (79%) had B-symptoms, eight (57%) had mediastinal disease, 10 (71%) had elevated serum lactate dehydrogenase (LDH) levels, and five (36%) had thrombocytopenia. All cases had CHL-like morphology but strongly expressed at least one B-cell marker. The neoplastic cells were Hodgkin and Reed-Sternberg-like cells, but with a large number of mononuclear variants. EBV-positive GZL patients were more significantly more likely than EBV-positive CHL patients to have advanced clinical stage (P = 0.023), presence of B-symptoms (P = 0.011), elevated serum LDH levels (P = 0.047), thrombocytopenia (P = 0.042), and mediastinal involvement (P = 0.023). The progression-free survival (PFS) of EBV-positive GZL patients was significantly poorer than that of EBV-positive CHL patients (P = 0.043) but no difference from EBV-positive DLBCL patients was observed (P = 0.367). CONCLUSIONS: EBV-positive GZL patients have significantly worse PFS than EBV-positive CHL patients, and are significantly more likely to have adverse clinical parameters such as advanced clinical stage, presence of B-symptoms, and thrombocytopenia. Further studies are needed to better characterize this entity, which may require the development of innovative therapeutic strategies.

FoxP3-positive T cell lymphoma arising in non-HTLV1 carrier: clinicopathological analysis of 11 cases of PTCL-NOS and 2 cases of mycosis fungoides.

AIMS: Forkhead box protein 3-positive (FoxP3(+) ) T cell lymphoma, in the absence of human T cell lymphotrophic virus type 1 (HTLV-1) infection, is rare and its clinicopathological characteristics still remain unclear. The aim of this study was to elucidate its characteristics. METHODS AND RESULTS: We describe here 11 cases of peripheral T cell lymphoma not otherwise specified (PTCL-NOS) and two cases of mycosis fingoides (MF) which were positive for FoxP3. The median age of the 11 PTCL-NOS cases was 65 years (range: 48-80 years), and all the patients were male. Eight patients (80%) showed stages III/IV disease, and six (60%) were categorized as high-intermediate/high-risk groups according to the International Prognostic Index. Two cases of MF were 57- and 59-year-old males. Both cases were categorized as stage IA, according to International Society for Cutaneous Lymphomas/European Organization of Research and Treatment of Cancer (ISCL/EORTC) classification. Immunohistochemically, all the cases were negative for cytotoxic molecule marker, and nine (75%) were αß T cell type. Scattered Epstein-Barr virus (EBV)-infected cells were detected in four cases of PTCL-NOS, implying the reactivation of EBV caused by the immunodeficient status of the patients. CONCLUSIONS: FoxP3(+) PTCL-NOS constitute a minor phenotypical subtype with poor prognosis and EBV reactivation in some. Conversely, two cases of MF showed an indolent clinical course which was different from previously reported cutaneous T cell lymphoma (CTCL) cases.

Analysis of potential genes, immunological and antioxidant profiles associated with trypanosomiasis susceptibility in dromedary camels.

Trypanosomiasis is associated with tissue damage and may trigger an immunological response. These tissue lesions are linked to metabolic issues and oxidative stress. The current study aimed to investigate the immunological, antioxidant, and metabolic changes that may be connected to camel trypanosomiasis. Blood samples were collected from 54 camels and allocated into two groups: The control group (35 camels) and the infected group (19 camels). The genes TLR2, TLR5, IL-17, MARCHF3, RASGRP1, EPS15L1, PPIE, ASB16, CMPK2, LPCAT1, FPGT, GPHN, TNNI3K, DIO3, keap1, and OXSR1 were significantly up-regulated in trypanosomiasis camels. However, down-regulation was observed for the genes Nrf2, PRDX6, and NDUFS5. PCR-DNA sequencing was used to identify nucleotide sequence polymorphisms in the immune (TLR2, TLR5, IL-17, MARCHF3, RASGRP1, and EPS15L1), metabolic (PPIE, ASB16, CMPK2, LPCAT1, FPGT, GPHN, TNNI3K, and DIO3), and antioxidant (Nrf2, Keap1, PRDX6, NDUFS5, and OXSR1) genes between healthy and trypanosomiasis-affected camels. Exploring the serum profile also showed a significant (P ˂ 0.05) increase in Hp, SAA, Cp, IL-1ß, IL-6, IL 10, TNF-α, and MDA, with significant (P ˂ 0.05) reduction in the serum levels of CAT, SOD, GSH, T3, and T4 in diseased camels compared with healthy ones. Our findings confirm the significance of nucleotide variations, gene expression patterns, and the biochemical profile of the investigated markers as indicators for the susceptibility of trypanosomiasis in dromedary camels and may be utilized to create management strategies.

Molecular networking-guided investigation of the secondary metabolome of four Morus species and their in vivo neuroprotective potential for the mitigation of Alzheimer's disease.

Alzheimer's Disease (AD) is a fatal age-related neurodegenerative condition with a multifactorial etiology contributing to 70% of dementia globally. The search for a multi-target agent to hit different targets involved in the pathogenesis of AD is crucial. In the present study, the neuroprotective effects of four Morus extracts were assessed in LPS-induced AD in mice. Among the studied species, M. macroura exhibited a profound effect on alleviating the loss of cognitive function, improved the learning ability, restored the acetylcholine esterase (AChE) levels to normal, and significantly reduced the tumor necrosis factor alpha (TNF-α) brain content in LPS-treated mice. To investigate the secondary metabolome of the studied Morus species, ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-HRMS/MS), aided with feature-based molecular networking, was employed. Among the annotated features, aryl benzofurans and prenylated flavonoids were suggested as being responsible for the observed neuroprotective effect. Furthermore, some of the detected metabolites were proposed as new natural products such as moranoline di-O-hexoside (1), isomers of trimethoxy-dihydrochalcone-O-dihexoside (59 & 76), (hydroxy-dimethoxyphenyl)butenone-O-hexoside (82), and O-methylpreglabridin-O-sulphate (105). In conclusion, our findings advocate the potential usage of M. macroura leaves for the management of AD, yet after considering further clinical trials.

Aflibercept or ranibizumab for diabetic macular edema.

Background: Vascular endothelial growth factor (VEGF) is the primary substance involved in retinal barrier breach. VEGF overexpression may cause diabetic macular edema (DME). Laser photocoagulation of the macula is the standard treatment for DME; however, recently, intravitreal anti-VEGF injections have surpassed laser treatment. Our aim was to evaluate the efficacy of intravitreal injections of aflibercept or ranibizumab for managing treatment-naive DME. Methods: This single-center, retrospective, interventional, comparative study included eyes with visual impairment due to treatment-naive DME that underwent intravitreal injection of either aflibercept 2 mg/0.05 mL or ranibizumab 0.5 mg/0.05 mL at Al-Azhar University Hospitals, Egypt between March 2023 and January 2024. Demographic data and full ophthalmological examination results at baseline and 1, 3, and 6 months post-injection were collected, including the best-corrected distance visual acuity (BCDVA) in logarithm of the minimum angle of resolution (logMAR) notation, slit-lamp biomicroscopy, dilated fundoscopy, and central subfield thickness (CST) measured using spectral-domain optical coherence tomography. Results: Overall, the 96 eyes of 96 patients with a median (interquartile range [IQR]) age of 57 (10) (range: 20-74) years and a male-to-female ratio of 1:2.7 were allocated to one of two groups with comparable age, sex, diabetes mellitus duration, and presence of other comorbidities (all P >0.05). There was no statistically significant difference in baseline diabetic retinopathy status or DME type between groups (both P >0.05). In both groups, the median (IQR) BCDVA significantly improved from 0.7 (0.8) logMAR at baseline to 0.4 (0.1) logMAR at 6 months post-injection (both P = 0.001), with no statistically significant difference between groups at all follow-up visits (all P >0.05). The median (IQR) CST significantly decreased in the aflibercept group from 347 (166) µm at baseline to 180 (233) µm at 6 months post-injection, and it decreased in the ranibizumab group from 360 (180) µm at baseline to 190 (224) µm at 6 months post-injection (both P = 0.001), with no statistically significant differences between groups at all follow-up visits (all P >0.05). No serious adverse effects were documented in either group. Conclusions: Ranibizumab and aflibercept were equally effective in achieving the desired anatomical and functional results in patients with treatment-naïve DME in short-term follow-up without significant differences in injection counts between both drugs. Larger prospective, randomized, double-blinded trials with longer follow-up periods are needed to confirm our preliminary results.

Detection of Sub-20 µm Microplastic Particles by Attenuated Total Reflection Fourier Transform Infrared Spectroscopy and Comparison with Raman Spectroscopy.

Microplastics are particulate water contaminants that are raising concerns regarding their environmental and health impacts. Optical spectroscopy is the gold standard for their detection; however, it has severe limitations such as tens of hours of analysis time and spatial resolution of more than 10 µm, when targeting the production of a 2D map of the microparticle population. In this work, through a single spectrum acquisition, we aim at quickly getting information about the whole population of identical particles, their chemical nature, and their size in a range below 20 µm. To this end, we built a compact setup enabling both attenuated total reflection Fourier transform infrared (ATR-FTIR) and Raman spectroscopy measurement on the same sample for comparison purposes. We used monodisperse polystyrene and poly(methyl methacrylate) microplastic spheres of sizes ranging between 6 and 20 µm, also measured collectively using a bench-top FTIR spectrometer in ATR mode. The ATR-FTIR technique appears to be more sensitive for the smallest particles of 6 µm, while the opposite trend is observed using Raman spectroscopy. We use theoretical modeling to simulate and explain the ripples observed in the measured spectra at the shortest wavelength (higher wavenumber) region, which appears as an indicator of the microparticle dimension. The latter finding opens new perspectives for ATR-FTIR for the identification and classification of populations of nearly identical micro-scale bodies, such as bacteria and other micro-organisms, where the same measured spectrum embeds dual information about the chemical nature and the size.

Substrate Signal Inhibition in Raman Analysis of Microplastic Particles.

In Raman analysis, the substrate material serves very often for signal enhancement, especially when metallic surfaces are involved; however, in other cases, the substrate has an opposite effect as it is the source of a parasitic signal preventing the observation of the sample material of interest. This is particularly true with the advent of microfluidic devices involving either silicon or polymer surfaces. On the other hand, in a vast majority of Raman experiments, the analysis is made on a horizontal support holding the sample of interest. In our paper, we report that a simple tilting of the supporting substrate, in this case, silicon, can drastically decrease and eventually inhibit the Raman signal of the substrate material, leading to an easier observation of the target analyte of the sample, in this case, microplastic particles. This effect is very pronounced especially when looking for tiny particles. Explanation of this trend is provided thanks to a supporting experiment and further numerical simulations that suggest that the lensing effect of the particles plays an important role. These findings may be useful for Raman analysis of other microscale particles having curved shapes, including biological cells.

Non-penetrating deep sclerectomy versus combined trabeculotomy-trabeculectomy in primary congenital glaucoma.

Background: The primary mode of therapy in children with primary congenital glaucoma (PCG) and mild or no corneal edema is goniotomy, which has a high success rate. However, in developing countries, the diagnosis of PCG is usually delayed, and corneal cloudiness interferes with goniotomy. Therefore, trabeculotomy may be the best choice in such eyes. We compared the short-term efficacy and safety of primary combined trabeculotomy-trabeculectomy (primary CTT) with that of non-penetrating deep sclerectomy (NPDS) in managing PCG. Methods: This prospective, randomized, comparative study included patients with PCG referred to Al-Azhar University Hospitals within a 1-year period. Eyes were randomly allocated to one of two groups: eyes in NPDS group underwent NPDS, and those in primary CTT group underwent primary CTT. Baseline and frequent postoperative assessments of intraocular pressure (IOP), cup-to-disc ratio (C/D ratio), corneal diameter, and axial length were performed for up to 6 months. The success rates were recorded in both groups. Results: Forty eyes of 26 patients were included, with 20 eyes allocated to each group. The mean (standard deviation) age of all patients was 12.9 (9.5) months, with comparable ages and sex ratios between groups (both P > 0.05). Both groups demonstrated a significant reduction in IOP and C/D ratio at each postoperative visit compared to the baseline visit (all P < 0.001), with no significant difference detected between the groups (all P > 0.05), except for a significantly lower IOP in NPDS group at 1 month (P < 0.05). The corneal diameter and axial length were comparable between groups at baseline and remained unchanged at all postoperative visits (all P > 0.05). The groups had comparable success rates (P > 0.05). No serious complications were detected. Conclusions: CTT and NPDS both yielded reasonable IOP control and reversal of cupping in eyes with PCG. We observed equal effectiveness of the surgical procedures without major safety concerns. Further large-scale clinical trials with longer follow-up periods are needed to verify our preliminary findings.

The effect of wet-cupping therapy (hijama) in modulating autoimmune activity of Hashimoto's thyroiditis: A pilot controlled study.

OBJECTIVES: To investigate the possible effects of wet-cupping therapy (hijama) on autoimmune activity and thyroid hormonal profiles of Hashimoto's disease (HD) patients. METHODS: A prospective pilot controlled trial was carried out among adult females following HD at the Endocrinology Clinic of King Abdulaziz University Hospital, Jeddah, Saudi Arabia, from February 2014 until March 2017. A total of 13 patients (intervention group) underwent 3 hijama sessions at 3-week interval with a 6-month follow-up. Blood tests were carried out for both pre- and post-hijama, including: thyroid peroxidase antibody (TPO), thyroglobulin antibody (TG), thyroid stimulating hormone (TSH), thyroxine-4 (T4), and prolactin. Control group included 13 randomly selected HD patients following usual care with 2 consecutive measurements of TPO and TG at 2-3 months interval. RESULTS: Changes in anti-TPO and anti-TG showed a decrease in hijama group versus an increase in control group, and intervention group comparison was statistically significant. On a fixed thyroxine supplement for each patient, significant decrease in levels of anti-TPO, anti-TG, TSH, prolactin, and erythrocyte sedi-mentation rate (ESR) occurred. CONCLUSION: These findings are presumptive to the efficacy of hijama on the pathogenesis of HD in modulating the immune inflammatory process demonstrated by the reduction in ESR, TPO, and TSH levels on a fixed thyroxin supplementation dose, along with patient-reported clinical improvement and positive changes in ultrasound including regaining of gland physiological size, echogenicity, and vascularity.

A microfluidic chip enables fast analysis of water microplastics by optical spectroscopy.

Microplastics contaminating drinking water is a growing issue that has been the focus of a few recent studies, where a major bottleneck is the time-consuming analysis. In this work, a micro-optofluidic platform is proposed for fast quantification of microplastic particles, the identification of their chemical nature and size, especially in the 1-100 µm size range. Micro-reservoirs ahead of micro-filters are designed to accumulate all trapped solid particles in an ultra-compact area, which enables fast imaging and optical spectroscopy to determine the plastic nature and type. Furthermore, passive size sorting is implemented for splitting the particles according to their size range in different reservoirs. Besides, flow cytometry is used as a reference method for retrieving the size distribution of samples, where chemical nature information is lost. The proof of concept of the micro-optofluidic platform is validated using model samples where standard plastic particles of different size and chemical nature are mixed.

Reference values and repeatability of pulsed-wave Doppler flowmetry of portal vein in healthy dromedary she-camels.

OBJECTIVE: This study was conducted to establish the normal values and repeatability of pulsed-wave (PW) Doppler ultrasonographic parameters of the hepatic portal circulation in healthy dromedary she-camels. MATERIALS AND METHODS: According to the American Society of Veterinary Clinical Pathology guidelines, the sample size and statistical analysis were followed. Ten healthy, non-pregnant, non-lactating she-camels were selected after physical, hematological, and ultrasonographic examinations. All hepatic ultrasonographic measurements were obtained from unsedated standing she-camels at the 11th right intercostal space using B-mode and PW Doppler. RESULTS: The ultrasonographic measurements were portal vein (PV) diameter 1.76 ± 0.37 cm; portal velocity 12.3 ± 3.2 cm/sec; portal area 2.05 ± 0.57 (cm)2; portal congestion index 0.16 ± 0.04 cms; and portal blood flow volume 0.02 ± 0.05 ml/sec/kg. The intra-assay coefficient of variations (CV)% of the above-mentioned variables were 5.84 ± 4.32, 12.3 ± 7.1, 10.5 ± 5.8, 14.7 ± 7.1, and 15.8 ± 12, respectively. However, the inter-assay CV% were 13.2 ± 5.9, 18.5 ± 8.4, 19.7 ± 7.6, 17.3 ± 8.8, and 31.9 ± 15, respectively. CONCLUSION: This study provides data that may be used as reference values for Doppler measurements of the PV in she-camels, which may help diagnose some hepatic disorders in camels.

Immunohistochemical Assessment of the Diagnostic Utility of PD-L1 (Clone SP142) for Methotrexate-Associated Lymphoproliferative Disorders With an Emphasis of Neoplastic PD-L1 (Clone SP142)-Positive Classic Hodgkin Lymphoma Type.

OBJECTIVES: We describe results of programmed death ligand 1 (PD-L1) immunohistochemical assessment in methotrexate (MTX)-associated lymphoproliferative disorders (LPDs) and highlight the characteristics of classic Hodgkin lymphoma (CHL) type MTX-LPD. METHODS: Fifty cases of MTX-LPD, including CHL type (n = 9), diffuse large B-cell lymphoma type (n = 15), and polymorphic B-cell LPD (n = 21), were investigated. RESULTS: Staining with anti-PD-L1 clone SP142 was exclusively found in CHL type (89%) but not in the others. Cases of CHL type MTX-LPD involved nodal disease and were associated with Epstein-Barr virus. They were histopathologically characterized by a vaguely nodular pattern, predominance of mononuclear cells, and strong expression of at least one pan-B-cell marker. Their clinical course was variable, with spontaneous regression in 5 patients, relapse in 2, and a fatal course in 1. CONCLUSIONS: The PD-L1 (clone SP142) workup aids the diagnostic approach to patients with MTX-LPD. CHL type MTX-LPD appears to represent a unique morphologic variant of CHL.

Prognostic Impact of MUM1/IRF4 Expression in Burkitt Lymphoma (BL): A Reappraisal of 88 BL Patients in Japan.

MUM1/IRF4 expression is detected in 18% to 41% of Burkitt lymphoma (BL). However, only a few studies of MUM1-positive (MUM1) BL have been reported, and its characteristics still remain controversial. To highlight the features of MUM1 BL, we compared the clinicopathologic characteristics of 37 cases of MUM1 and 51 cases of MUM1-negative (MUM1) BL in Japan. Compared with MUM1 BL, patients with MUM1 BL showed significantly younger onset (P=0.0062) and a higher ratio of females (P=0.013). We have also revealed the difference in the involved sites. The MUM1 group showed lower incidences of involvement of stomach (P=0.012) and tonsil (P=0.069). There was a more tendency in MUM1 group to involve colon (P=0.072), breast (P=0.073), and kidney (P=0.073). Regarding the prognosis, a trend toward a lower overall survival for MUM1 group was noted (P=0.089). Notably, comparing MUM1 and MUM1 BL cases of adults (age16 y old and above), the former showed significantly worse prognosis (P=0.041). Among the BL patients treated with the intensive chemotherapy, a standard therapy for BL, MUM1 cases showed worse prognosis (P=0.056). In conclusion, MUM1 BL showed worse prognosis, particularly in adult cases, compared with MUM1 BL. In addition, the difference of the onset age, sex ratio, and involved sites between the 2 groups was noted. Our results demonstrate that MUM1 expression might predict worse prognosis of BL, and MUM1 BL should be distinguished from MUM1 BL.

Evaluation of hypolipidemic Marrubium vulgare effect in Triton WR-1339-induced hyperlipidemia in mice.

OBJECTIVE: To evaluate the hypocholesterolemic and hypotriglyceridemic activities of four Marrbium vulgare herb extracts using Triton WR-1339-induced hyperlipidemia in mice. METHODS: Hyperlipidemia was developed by intraperitoneal injection of Triton (200 mg/kg body weight). The animals were divided into main four groups of eight mice each: normal control group, hyperlipidemic control group, hyperlipidemic plus tween-40 control and treated group. The fourth one was divided into four subgroups, petroleum ether extract group, chloroform extract group, ethyl acetate extract group and methanol extract treated group each of them contains two sub-sub group for treating animals with two doses at 0.1 and 0.25 LD50. RESULTS: After 7 h and 24 h of treatment, the intragastric administration of all extracts caused a significant decrease of plasma total cholesterol. Triglyceride levels were also significantly lowered by all extracts while petroleum ether produced the lowest decreasing level. Similar results were observed for LDL-cholesterol concentrations. Furthermore, more polar extracts (methanol and ethyl acetate)-soluble fractions showed a significant ameliorative action on elevated atherogenic index (AI) and LDL/HDL-C ratios, while these atherogenic markers were not statistically suppressed by the chloroform and petroleum ether-soluble extract. CONCLUSION: The findings indicated that Marrubium may contain polar products able to lower plasma lipid concentrations and might be beneficial in treatment of hyperlipidemia and atherosclerosis.

Molecular subtypes of breast carcinoma in Egyptian women: clinicopathological features.

Breast carcinoma may be classified into distinct molecular subtypes based on immunohistochemical markers for estrogen, progesterone and Her-2/neu receptors. The aim of the study was to identify the clinicopathological features of the molecular subtypes of breast carcinoma in our locality. A total of 274 surgically resected breast carcinomas were selected from the files of the Dr. KRZ referral pathology laboratory, Mansoura, Egypt, and the Pathology Department of Mansoura University. Molecular subtypes were classified into luminal A, luminal B, Her-2/neu-expressing and triple-negative. Clinicopathological and histological features of molecular subtypes were analyzed. Luminal A subtype was the most prevalent (41.2%), followed by triple-negative subtype (28.5%), then Her2-expressing subtype (19.4%) and luminal B subtype (13.9%). The commonest histological type was infiltrating duct carcinoma (83.2%), followed by infiltrating lobular carcinoma (9.1%) and medullary carcinoma (3.2%). The luminal A subtype was significantly correlated to low tumor grade, lower number of positive lymph nodes metastasis, absence of both necrosis and syncytial growth pattern. We concluded that the commonest molecular subtype of invasive breast carcinoma among Egyptian women is luminal subtype A, which displayed favorable features. Triple-negative subtype and medullary carcinomas are present in a ratio higher than in western countries.

Immediate breast reconstruction with expander assisted latissimus dorsi flap after skin sparing mastectomy.

BACKGROUND AND PURPOSE: The latissimus dorsi myocutaneous flap (LDMF) used to be the standard practice for breast reconstruction; however, with the increased use of tissue expanders and the development of the transverse rectus-abdominis myocutaneous flap for autologous tissue breast reconstruction, its use has decreased. To reassess the role of the LDMF in breast reconstruction, a prospective study was performed to evaluate women who had a skin sparing mastectomy followed by immediate reconstruction with a latissimus dorsi flap and tissue expander implant. PATIENTS AND METHODS: Twenty-five women with early breast cancer underwent immediate latissimus dorsi myocutaneous flaps with tissue expander after skin sparing mastectomy. The oncologic safety of skin sparing mastectomy, the postoperative aesthetic results and complications were evaluated. RESULTS: Between May 2003 and April 2005, 25 consecutive women diagnosed with breast cancer underwent skin sparing mastectomy and expander assisted immediate latissimus dorsi breast reconstruction. Their median age was 42 years, ranging from 34 to 48 years. The procedure duration ranged from 2.5 to 6 hours, with a median of 3.9 hours, however, expansion was completed by 4 months (range 1 to 8 months). Patients were discharged 7 days after surgery with a range of 5 to 15 days. The complication rate was low, manifesting with skin flap necrosis in 12%, wound infection in 4%, and port site extrusion in 4%. There was no flap loss. With the exception of seroma formation, the donor site morbidity was low (seroma 40%, hematoma 4%, back pain 8%, and limited arm movement 4%). No local recurrence was recorded. The aesthetic result of surgery was rated as excellent in 20%, good in 60%, fair in 24%, and poor in 4% of cases. The duration of post-operative follow up was 14.7 months, ranging from 6 to 24 months. CONCLUSIONS: Skin sparing mastectomy and immediate breast reconstruction is an oncologically safe technique. The use of latissimus dorsi myocutaneous flap with tissue expansion has proved to be an effective and aesthetic method of immediate breast reconstruction after skin sparing mastectomy.