Tumor microenvironment and immune system preservation in early-stage breast cancer: routes for early recurrence after mastectomy and treatment for lobular and ductal forms of disease.

BACKGROUND: Intra-ductal cancer (IDC) is the most common type of breast cancer, with intra-lobular cancer (ILC) coming in second. Surgery is the primary treatment for early stage breast cancer. There are now irrefutable data demonstrating that the immune context of breast tumors can influence growth and metastasis. Adjuvant chemotherapy may be administered in patients who are at a high risk of recurrence. Our goal was to identify the processes underlying both types of early local recurrences. METHODS: This was a case-control observational study. Within 2 years of receiving adjuvant taxan and anthracycline-based chemotherapy, as well as modified radical mastectomy (MRM), early stage IDC and ILC recurred. Vimentin, α-smooth muscle actin (SMA), platelet-derived growth factor (PDGF), matrix metalloproteinase (MMP1), and clustered differentiation (CD95) were investigated. RESULTS: Of the samples in the ductal type group, 25 showed local recurrence, and 25 did not. Six individuals in the lobular-type group did not experience recurrence, whereas seven did. Vimentin (p = 0.000 and 0.021), PDGF (p = 0.000 and 0.002), and CD95 (p = 0.000 and 0.045) expressions were significantly different in ductal and lobular carcinoma types, respectively. Measurement of ductal type was the sole significant difference found in MMP1 (p = 0.000) and α-SMA (p = 0.000). α-SMA and CD95 were two variables that helped the recurrence mechanism in the ductal type according to the pathway analysis. In contrast, the CD95 route is a recurrent mechanism for the lobular form. CONCLUSIONS: While the immune system plays a larger role in ILC, the tumor microenvironment and immune system both influence the recurrence of IDC. According to this study, improving the immune system may be a viable cancer treatment option.

Numerical simulation based performance enhancement approach for an inorganic BaZrS3/CuO heterojunction solar cell.

One of the main components of the worldwide transition to sustainable energy is solar cells, usually referred to as photovoltaics. By converting sunlight into power, they lessen their reliance on fossil fuels and the release of greenhouse gases. Because solar cells are decentralized, distributed energy systems may be developed, which increases the efficiency of the cells. Chalcogenide perovskites have drawn interest due to their potential in solar energy conversion since they provide distinctive optoelectronic characteristics and stability. But high temperatures and lengthy reaction periods make it difficult to synthesise and process them. Therefore, we present the inaugural numerical simulation using SCAPS-1D for emerging inorganic BaZrS3/CuO heterojunction solar cells. This study delves into the behaviour of diverse parameters in photovoltaic devices, encompassing efficiency (η) values, short-circuit current density (Jsc), fill factor (FF), and open-circuit voltage (Voc). Additionally, we thoroughly examine the impact of window and absorber layer thickness, carrier concentration, and bandgap on the fundamental characteristics of solar cells. Our findings showcase the attainment of the highest efficiency (η) values, reaching 27.3% for our modelled devices, accompanied by Jsc values of 40.5 mA/cm2, Voc value of 0.79 V, and FF value of 85.2. The efficiency (η) values are chiefly influenced by the combined effects of Voc, Jsc, and FF values. This optimal efficiency was achieved with CuO thickness, band gap, and carrier concentration set at 5 µm, 1.05 eV, and above 1019 cm-3, respectively. In comparison, the optimal parameters for BaZrS3 include a thickness of 1 µm, a carrier concentration below 1020 cm-3, and a band gap less than 1.6 eV. Therefore, in the near future, the present simulation will simultaneously provide up an entirely novel field for the less defective perovskite solar cell.

Normal and pathological findings for the facial nerve on magnetic resonance imaging.

AIM: To demonstrate the enhanced radiological anatomy and common pathological conditions of the facial nerve by using magnetic resonance imaging (MRI). MATERIALS AND METHODS: A retrospective review of the MRI findings of the facial nerve of 146 patients who visited a tertiary academic referral center was conducted. RESULTS: The radiological anatomy of the facial nerve was well illustrated using MRI, as were most of the common pathological conditions of the facial nerve. CONCLUSIONS: Enhancement of the facial nerve in MRI should be correlated with the clinical data. Normal individuals can show enhancement of the tympanic or vertical segments of the facial nerve. Enhancement of the labyrinthine portion of the nerve is almost diagnostic of Bell's palsy. No specific enhancement patterns were observed for tumours or for infections of the middle or external ear. A larger population study is required for the accurate assessment of facial nerve enhancement in multiple sclerosis patients.

Reliability of the Mangled Extremity Severity Score in the Management of Peripheral Vascular Injuries in Children: A Retrospective Review.

This study was aimed to evaluate different management modalities for peripheral vascular trauma in children, with the aid of the Mangled Extremity Severity Score (MESS). A single-center retrospective analysis took place between 2010 and 2017 at University Hospitals, having emergencies and critical care centers. Different types of vascular repair were adopted by skillful vascular experts and highly trained pediatric surgeons. Patients were divided into three different age groups. Group I included those children between 5 and 10 years; group II involved pediatrics between 11 and 15 years; while children between 16 and 21 years participated in group III. We recruited 183 children with peripheral vascular injuries. They were 87% males and 13% females, with the mean age of 14.72 ± 04. Arteriorrhaphy was performed in 32%; end-to-end anastomosis and natural vein graft were adopted in 18% and 29% respectively. On the other hand, 20% underwent bypass surgery. The age groups I and II are highly susceptible to penetrating trauma ( p = 0.001), while patients with an extreme age (i.e., group III) are more susceptible to blunt injury ( p = 0.001). The MESS has a significant correlation to both age groups I and II ( p = 0.001). Vein patch angioplasty and end-to-end primary repair should be adopted as the main treatment options for the repair of extremity vascular injuries in children. Moreover, other treatment modalities, such as repair with autologous vein graft/bypass surgery, may be adopted whenever possible. They are cost-effective, reliable, and simple techniques with fewer postoperative complication, especially in poor/limited resources.

Erratum to: Reliability of the Mangled Extremity Severity Score in the Management of Peripheral Vascular Injuries in Children: A Retrospective Review.

[This corrects the article DOI: 10.1055/s-0040-1720970.].

Regulation of Angiogenesis Discriminates Tissue Resident MSCs from Effective and Defective Osteogenic Environments.

BACKGROUND: The biological mechanisms that contribute to atrophic long bone non-union are poorly understood. Multipotential mesenchymal stromal cells (MSCs) are key contributors to bone formation and are recognised as important mediators of blood vessel formation. This study examines the role of MSCs in tissue formation at the site of atrophic non-union. MATERIALS AND METHODS: Tissue and MSCs from non-union sites (n = 20) and induced periosteal (IP) membrane formed following the Masquelet bone reconstruction technique (n = 15) or bone marrow (n = 8) were compared. MSC content, differentiation, and influence on angiogenesis were measured in vitro. Cell content and vasculature measurements were performed by flow cytometry and histology, and gene expression was measured by quantitative polymerase chain reaction (qPCR). RESULTS: MSCs from non-union sites had comparable differentiation potential to bone marrow MSCs. Compared with induced periosteum, non-union tissue contained similar proportion of colony-forming cells, but a greater proportion of pericytes (p = 0.036), and endothelial cells (p = 0.016) and blood vessels were more numerous (p = 0.001) with smaller luminal diameter (p = 0.046). MSCs showed marked differences in angiogenic transcripts depending on the source, and those from induced periosteum, but not non-union tissue, inhibited early stages of in vitro angiogenesis. CONCLUSIONS: In vitro, non-union site derived MSCs have no impairment of differentiation capacity, but they differ from IP-derived MSCs in mediating angiogenesis. Local MSCs may thus be strongly implicated in the formation of the immature vascular network at the non-union site. Attention should be given to their angiogenic support profile when selecting MSCs for regenerative therapy.

Studies on the application of immobilization technique for the production of cyclosporin A by a local strain of Aspergillus terreus.

The formation of cyclosporin A (Cy A) by immobilized spores and mycelia of Aspergillus terreus was investigated. Different carriers were tested as immobilizing carriers, whereby Ca-alginate was selected for further experimentation. The role of alginate concentration, biomass weight, pH value of the cultivation medium, repeated utilization of the immobilized fungus as well as the supplementation of different amino acid precursors were studied. Best Cy A outputs were attained with Ca-alginate 3% (w/v), mycelial weight 15% (w/v), pH 4.5 and four repeated cycles. Similarly, the Cy A productivity was markedly accelerated in the presence of L-valine and L-valine and L-leucine mixture.

Role of some fermentation parameters on cyclosporin A production by a new isolate of Aspergillus terreus.

A local isolate of Aspergillus terreus was selected among different microorganisms as a new cyclosporin A (Cy A) producing culture. The formation of Cy A was investigated under different fermentation conditions (including selection of the cultivation medium, fermentation time course, inoculum nature, medium volume, agitation rate, pH value). Relatively high Cy A productivities were maintained when the fermentation process was carried out using a medium composed of (g/L): glucose, 50; bactopeptone, 10; KH(2)PO(4), 5; KCl, 2.5; pH 5.3, inoculated with 2% standard inoculum of 48 h age, shaken at 200 rpm for 10 days.

Further experience with 2100 consecutive ketamine administrations: newer indications and restrictions.

Two thousand one hundred consecutive administrations of ketamine as an anaesthetic agent are reviewed. On the basis of the experience described, the authors assess that this agent could be used with safety in the average patient presenting for surgery and that it would be likely to suffice as the sole anaesthetic agent in 40% of such cases but would require supplementation by other anaesthetic agents in the remaining 60% of cases. They recommend it as being particularly useful in children submitting to dental surgery as it can be used without sedative premedication and permits of rapid recovery.

Sirolimus produced S-shaped effect on adult polycystic kidneys after 2-year treatment.

This double-blind trial followed 16 patients with autosomal dominant polycystic kidney disease (ADPKD) who received telmisartan or sirolimus plus telmisartan for 24 months. The 6-month pilot study showed a promising effect of sirolimus. The primary metric of this 2-year study was the change in total kidney volume at 12 and 24 months, as measured on magnetic resonance imaging. Secondary outcome was changes in renal function from the baseline at months 12 and 24. Among patients receiving sirolimus, the mean total kidney volume increased from 2845 mL to 3381 mL at 1 year and to 3901 mL at 2 years versus placebo values increasing from 2667 mL to 3680 mL and 3776 mL, respectively. The posttreatment mean total kidney volume increased less on sirolimus (P = .07) versus control therapy (P = .05) after 1 year, but there was no difference at 24 months. Kidney volume was stable on sirolimus to 12 months, increasing steadily to 24 months. In contrast, kidney volume increased steadily among patients on telmisartan alone both at 12 and 24 months. In conclusion, sirolimus appeared to retard kidney growth among patients with ADPKD during the first 6 months of therapy but not to halt growth thereafter, thus eliciting S-shaped effect. The dose of sirolimus (1 mg per day) was associated with a low rate of side effects similar those observed in kidney transplantation.

OPTIMIZATION OF SOME HEAVY METALS BIOSORPTION BY REPRESENTATIVE EGYPTIAN MARINE ALGAE(1).

Marine algae-as inexpensive and renewable natural biomass-have attracted the attention of many investigators to be used to preconcentrate and biosorb many heavy metal ions. Impressed by this concept, the metal uptake capacity of Egyptian marine algae was examined using representatives of green and brown algae, namely, Ulva lactuca L. and Sargassum latifolium (Turner) C. Agardh, respectively. The biosorption efficiencies of Cu(2+) , Co(2+) , Ni(2+) , Cd(2+) , Hg(2+) , Ag(2+) , and Pb(2+) ions seem to depend on the type of the algae used as well as the conditions under which the uptake processes were conducted. It was demonstrated that a pH range of 7.5-8.8 was optimum for the removal of the tested metals. Similarly, the uptake process was markedly accelerated during the first 2 h using relatively low metal level and sufficient amounts of the dried powdered tested algae.

Human papilloma virus in head and neck squamous cell cancer.

BACKGROUND: Epidemiologic and molecular evidences have established a strong link between high risk types of Human Papilloma Virus and a subgroup of Head and Neck Squamous Cell Carcinomas (HNSCC). We evaluated the frequency of HPV positivity in HNSCC and its relationship to demographic and some risk factor variables in an open case- control study. METHODS: Fourteen recently diagnosed patients with squamous cell cancer of oropharynx, hypopharynx and larynx aged 18-50 years were examined from 2008-2010 in Tabriz, Iran. HPV DNA was extracted from paraffin-embedded blocks of each patient's sample for PCR evaluation. Saliva samples of 94 control cancer-free subjects were collected for DNA analysis. Multivariable logistic regression method was used to calculate odds ratio for case-control comparisons. RESULTS: High risk HPV was detected in 6(42.8%) patients, and 6(5.3%) control subjects which was statistically significant (p<0.0001). HPV-18 was the most frequent type both in the cases and controls. HPV-16 DNA was detected in two patients of the case group, but it was not detected in any of the controls. The relation between demographic and risk factor variables was not statistically significant. CONCLUSION: HPV infection has a significant impact on HNSCC. Despite HPV-16 stronger impact, HPV-18 is more likely to cause malignant degeneration in such cancers amongst some communities. It is vital to introduce and conduct immunization schedules in health care systems to protect communities to some extent.

Serum amyloid A protein and hypoxic ischemic encephalopathy in the newborn.

OBJECTIVE: Serum amyloid A (SAA) is an acute phase inflammatory marker that is closely associated with ischemic injuries. Its expression in neonatal hypoxic ischemic encephalopathy (HIE) has not been studied. To test the hypothesis that SAA is increased in neonatal HIE and its concentration correlates with the severity of encephalopathy. STUDY DESIGN: We conducted a prospective case-control study on 54 full-term neonates; 27 cases with evidence of perinatal compromise and 27 healthy controls. Blood samples were collected from cases and controls at postnatal day 1 and day 7, and SAA was measured by ELISA. RESULTS: SAA concentrations (µg ml(-1)) were significantly increased in cases when compared with controls at day 1 and at day 7 (P<0.001). SAA concentrations at day 1 were greater in cases who died when compared with those who survived, and correlated significantly with the severity of HIE (146.9 ± 56.4 vs 79.8 ± 24.7 vs 58.1 ± 21.5) in severe, moderate and mild HIE, respectively (P=0.001). CONCLUSIONS: The expression of SAA is increased in response to hypoxia ischemia of the neonate. The increased concentration correlates with the severity of encephalopathy and is associated with mortality. This is the first study of SAA in neonatal HIE.

Structural and ultrastructural evidence of neurotoxic effects of fried potato chips on rat postnatal development.

OBJECTIVE: Acrylamide (ACR), a proved rodent carcinogen and neurotoxic agent, is present in significant quantities in commonly consumed foods such as fried potato chips (FPC) and French fries, raising a health concern worldwide. We investigated and compared the neurotoxic effects of ACR and FPC on postnatal development. METHODS: Female rats were treated with ACR (30 mg/kg of body weight), fed a diet containing approximately 30% of FPC during pregnancy, or fed a standard diet (control) and their offspring were examined. RESULTS: Female rats treated with ACR or fed a diet containing FPC during pregnancy gave birth to litters with delayed growth and decreased body and brain weights. Light microscopic studies of the cerebellar cortex of treated animals revealed drastic decreases in Purkinje cells and internal granular layers. Different patterns of cell death were detected in Purkinje cells and neurons in the brains of pups born to treated mothers. Ultrastructural analysis of Purkinje cells revealed changes in the endoplasmic reticulum, loss of the normal arrangement of polyribosomes, swollen mitochondria with abnormally differentiated cristae, and an abnormal Golgi apparatus. The gastrocnemius muscle in the ACR and FPC groups showed extensive degeneration of myofibrils as evidenced by poorly differentiated A, H, and Z bands. CONCLUSION: The present study reveals for the first time that rat fetal exposure to ACR, as a pure compound or from a maternal diet of FPC, causes cerebellar cortical defects and myodegeneration of the gastrocnemius muscle during the postnatal development of pups. These results warrant a systematic study of the health effects of the consumption of FPC and French fries in the general population.

Sirolimus therapy for patients with adult polycystic kidney disease: a pilot study.

A pilot study was performed on adult polycystic kidney disease (PCKD) patients to examine the effects of the anti-proliferative mammalian target of rapamycin inhibitor sirolimus on the growth of renal cysts. Eight consecutive PCKD patients were given sirolimus (1 mg/d PO) for 6 consecutive months, in addition to an angiotensin receptor blocker (ARB), namely telmisartan. Another 8 PCKD patients served as a control group given only telmisartan. All PCKD patients had a serum creatinine value <2 mg/dL with a negative urine culture before enrollment. All patients were diagnosed by renal magnetic resonance imaging (MRI) to measure renal volumes. After a 6-month follow-up, patients were rescanned to remeasure the MRI volumes. Renal function was stable in 5/8 subjects in the sirolimus group, improved in 2 cases, and worsened in 1 with an increase of serum creatinine to >2 mg/dL resulting in his withdrawal after 5 months of follow-up. In contrast, the serum creatinine value was stable in 3 control group subjects, worsen in 3, and improved in 2. Four patients in the sirolimus group experienced infectious complications, namely, urinary tract infections (UTI) in 2 which were treated with antibiotics, and monilial pharyngitis in 2, who were treated and cured with a topical antifungal. In the control group, only 2 developed and were treated for UTIs. Hematologic tests were normal in all patients. There was an insignificant rise in kidney volume as measured by MRI in the sirolimus group (2845 vs 3221 mL after 6 months; P = NS) compared with a significant increase in the control group (2667 vs 3590 mL after 6 months; P < .05). We concluded that sirolimus, in addition to an ARB, might be beneficial for PCKD patients who present early in their illness.

A study for evaluation of different diagnostic approaches in acute leukemia in Egypt.

Cytomorphology, cytochemistry, immunophenotyping, in addition to cytogenetic and molecular analyses have specific roles in the diagnosis and management of acute leukemias. This work was designed as a comparative study of different available methods for diagnosis of acute leukemia. The study comprised 47 cases with acute leukemia (21 cases with ALL and 26 cases with AML). Peripheral blood and bone marrow samples were subjected to through morphological examination of Leishman-stained smears, cytochemical analysis, immunophenotyping, conventional cytogenetic banding analysis, fluorescence in situ hybridization (FISH) for selected cases, and RT-PCR for detection of BCR-ABL rearrangement. The results of the study revealed that careful examination of Romanowsky-stained peripheral blood and BM films is fundamental in the diagnosis of acute leukemias, and when considered together with clinical and hematological features, indicates which of the more specialized techniques are most likely to be useful. The major role of cytochemistry was in the diagnosis of AML, while the major role of immunophenotyping was in the diagnosis of acute leukemia, which is not obviously myeloid. Apart from identification of chromosomal abnormalities unique to specific subtypes of leukemia, cytogenetic analysis had a salient impact on anticipating the prognosis and treatment outcome in acute leukemias. We could conclude that the techniques used in this study are considered complementary rather than alternatives and that stepwise employment of strategies is more cost effective than doing all the tests simultaneously.

Influence of gamma-irradiation and maize lipids on the production of aflatoxin B1 by Aspergillus flavus.

The effect of gamma-irradiation and maize lipids on aflatoxin B1 production by Aspergillus flavus artificially inoculated into sterilized maize at reduced water activity (aw 0.84) was investigated. By increasing the irradiation doses the total viable population of A. flavus decreased and the fungus was completely inhibited at 3.0 kGy. The amounts of aflatoxin B1 were enhanced at irradiation dose levels 1.0 and 1.5 kGy in both full-fat maize (FM) and defatted maize (DM) media and no aflatoxin B1 production at 3.0 kGy gamma-irradiation over 45 days of storage was observed. The level in free lipids of FM decreased gradually, whereas free fatty acid values and fungal lipase activity increased markedly by increasing the storage periods. The free fatty acid values decreased by increasing the irradiation dose levels and there was a significant enhancement of fungal lipase activity at doses of 1.0 and 1.50 kGy. The ability of A. flavus to grow at aw 0.84 and produce aflatoxin B1 is related to the lipid composition of maize. The enhancement of aflatoxin B1 at low doses was correlated to the enhancement of fungal lipase activity.

Malignancy: Identification of Predictors of Disease Status and Progression in Patients with Myeloma (MM).

Multiple studies have attempted to recognize the best markers of disease activity and outcome in myeloma (MM). Our objective was to identify the best variables that can reflect MM disease status. Design and methods: The data obtained from all the following tests were included in the analysis: serum levels of the 2 growth factors known to be crucial for MM growth (i.e. IL-6, and sIL-6R), routine peripheral blood data (Hb%, serum calcium, albumin, CRP, B2m, LDH) and bone marrow plasma cell (BMPC)%, as well as the age and sex of patients. The study was conducted on 21 cases of MM under chemotherapy (aged 48-74 years; M/F = 13/8) and 12 matched normal individuals. The patients were categorized into 2 groups according to their clinical status: Group#1 (n = 16; cases in plateau/stable phase), and Group#2 (n = 5; advanced/refractory cases). Results: Student t-test confirms that serum IL-6 and sIL-6R are the most statistically different variables upon comparing cases in plateau phase (Group#1) with those of advanced disease (Group#2). Stepwise discriminant analysis of data has resulted in a function that is composed of the 2 most salient variables (i.e. serum IL-6, sIL-6R). The proposed function was highly significant (p = 0.0000) with Wilk's Lambda = 0.02538. The diagnostic capability of the proposed function was very high (percent of grouped cases that were classified correctly= 100%). Conclusion: measurement of serum IL-6 and sIL-6R gives the best prediction of disease activity in patients with MM.