Nebivolol ameliorates sepsis-evoked kidney dysfunction by targeting oxidative stress and TGF-ß/Smad/p53 pathway.

Sepsis is a potential fetal organ destruction brought on through an overzealous immunologic reaction to infection, causing severe inflammation, septic shock, and damage to different organs. Although there has been progress in the identification and controlling of clinical sepsis, the fatality rates are still significant. This study, for the first time, intended to examine the possible ameliorative impact of Nebivolol, a ß1-adrenergic antagonist antihypertensive drug, against nephrotoxicity resulted from cecal ligation and puncture (CLP)-induced sepsis in rats, on molecular basis. Sixty male Wistar albino rats were chosen. Oxidative stress indicators and biochemical markers of kidney activity were evaluated. Inflammatory mediators, fibrosis- and apoptosis-related proteins and gene expressions were investigated. Moreover, renal histopathological investigation was performed. CLP-induced nephrotoxicity characterized by markedly elevated serum levels of creatinine, blood urea nitrogen, uric acid, and renal malondialdhyde. On the other hand, it decreased serum total protein level, renal superoxide dismutase activity and reduced glutathione level. Additionally, it significantly elevated the renal inflammatory mediators (tumor necrosis factor-alpha, ilnerlukin (IL)-6, and IL-1ß) and Caspase-3 protein, reduced IL-10 level, amplified the expression of transforming growth factor-beta 1 (TGF-ß1), p-Smad2/3 and alpha-smooth-muscle actin proteins, downregulated the B cell lymphoma-2 (Bcl-2) gene and elevated the transcription of Bcl-2-associated X-protein (Bax), p53 and Nuclear factor-kappa B (NF-κB) genes. Furtheremor, kidney tissues exhibited significant histopathological changes with CLP. On the contrary, Nebivolol significantly improved all these biochemical changes and enhanced the histopathological alterations obtained by CLP. This research showed, for the first time, that Nebivolol effectively mitigated the CLP-induced kidney dysfunction via its antioxidant, antifibrotic and anti-apoptotic activity through modulation of oxidative stress, TGF-ß/NF-κB and TGF-ß/Smad/p53 signaling pathways.

Comprehensive identification, characterization, and expression analysis of the MORF gene family in Brassica napus.

BACKGROUND: RNA editing in chloroplast and mitochondrion transcripts of plants is an important type of post-transcriptional RNA modification in which members of the multiple organellar RNA editing factor gene family (MORF) play a crucial role. However, a systematic identification and characterization of MORF members in Brassica napus is still lacking. RESULTS: In this study, a total of 43 MORF genes were identified from the genome of the Brassica napus cultivar "Zhongshuang 11". The Brassica napus MORF (BnMORF) family members were divided into three groups through phylogenetic analysis. BnMORF genes distributed on 14 chromosomes and expanded due to segmental duplication and whole genome duplication repetitions. The majority of BnMORF proteins were predicted to be localized to mitochondria and chloroplasts. The promoter cis-regulatory element analysis, spatial-temporal expression profiling, and co-expression network of BnMORF genes indicated the involvement of BnMORF genes in stress and phytohormone responses, as well as growth and development. CONCLUSION: This study provides a comprehensive analysis of BnMORF genes and lays a foundation for further exploring their physiological functions in Brassica napus.

GATA3 Positively Correlates with BCL2 Expression in Indolent and Aggressive Histological Types of Cutaneous Basal Cell Carcinoma.

OBJECTIVE: Some histological basal cell carcinoma (BCC) types demonstrate more aggressive behavior than others. They are known as high-risk BCC and are more challenging in therapy, contrary to indolent (low-risk) BCC types. Identifying novel protein markers to predict aggressiveness and potential therapeutic targets in challenging cases is recommended. GATA3 is a transcription factor critical for epithelial and lymphocytic differentiation. This study investigated the immunohistochemical expression of GATA3 in indolent and aggressive BCC and its association with BCL2 expression. MATERIAL AND METHODS: Retrospectively collected indolent and aggressive BCC groups (24 cases each) were immunohistochemically stained with anti-GATA3 and BCL2 antibodies. The mean expression score (by area percentage) and TIL counts were determined and compared using ImageJ analysis. Stromal tumor-infiltrating lymphocytes (TIL) were counted per high-power field (HPF) on hematoxylin and eosin (H&E) staining. RESULTS: GATA3 and BCL2 expressions were significantly higher in the indolent group than in the aggressive group. GATA3 expression significantly correlated with BCL2 score and TIL counts. Higher GATA3 expression was significantly associated with a more indolent BCC histological type, higher BCL2 expression, and higher TIL count. CONCLUSION: GATA3 is a possible target for immunomodulation experiments to improve BCC immunotherapy outcomes.

Immunohistochemical Expression of Vitamin D Receptor (VDR) in Urinary Bladder Squamous Cell Carcinoma.

OBJECTIVE: Squamous cell carcinoma (SCC) of the urinary bladder is associated with aggressive behavior and is typically treated with radical cystectomy. Vitamin D receptor (VDR) and its ligand Calcitriol have shown anti-tumor effects in various malignancies but to our knowledge there is no current information on VDR expression in bladder SCC. This study aimed to assess VDR immunostaining patterns in pure bladder SCC and its relation to the available clinicopathological parameters of such tumors. MATERIAL AND METHODS: VDR immunostaining was performed on 35 radical cystectomy specimens from patients with primary pure SCC. Nuclear and cytoplasmic VDR staining was scored separately using the semi-quantitative immunoreactive score. RESULTS: Nuclear and cytoplasmic/membranous VDR expression was present in 35 (100%) and 19 (54.3%) cases, respectively, with a significant negative linear relationship (r=-0.33; p=0.035). Differences in cytoplasmic/membranous VDR expression were found in relation to tumor histology (p=0.018), tumor necrosis (p=0.022), and stage groups (p=0.001). Low cytoplasmic VDR correlated with increased tumor staging (Cc = -0.422), positive lymph node status (Cc = -0.375), and higher stage groups (Cc= -0.438). The median nuclear VDR expression score was significantly higher in advanced stage groups (p= 0.038). CONCLUSION: Our data suggest that VDR may be a potential prognostic factor in bladder SCC. Further studies and clinical trials using vitamin D supplements may provide a new therapeutic option for those high-risk patients.

Recent advances and biotechnological applications of RNA metabolism in plant chloroplasts and mitochondria.

The chloroplast and mitochondrion are semi-autonomous organelles that play essential roles in cell function. These two organelles are embellished with prokaryotic remnants and contain many new features emerging from the co-evolution of organelles and the nucleus. A typical plant chloroplast or mitochondrion genome encodes less than 100 genes, and the regulation of these genes' expression is remarkably complex. The regulation of chloroplast and mitochondrion gene expression can be achieved at multiple levels during development and in response to environmental cues, in which, RNA metabolism, including: RNA transcription, processing, translation, and degradation, plays an important role. RNA metabolism in plant chloroplasts and mitochondria combines bacterial-like traits with novel features evolved in the host cell and is regulated by a large number of nucleus-encoded proteins. Among these, pentatricopeptide repeat (PPR) proteins are deeply involved in multiple aspects of the RNA metabolism of organellar genes. Research over the past decades has revealed new insights into different RNA metabolic events in plant organelles, such as the composition of chloroplast and mitochondrion RNA editosomes. We summarize and discuss the most recent knowledge and biotechnological implications of various RNA metabolism processes in plant chloroplasts and mitochondria, with a focus on the nucleus-encoded factors supporting them, to gain a deeper understanding of the function and evolution of these two organelles in plant cells. Furthermore, a better understanding of the role of nucleus-encoded factors in chloroplast and mitochondrion RNA metabolism will motivate future studies on manipulating the plant gene expression machinery with engineered nucleus-encoded factors.

Tranexamic acid versus misoprostol for management of postpartum hemorrhage: A systematic review and meta-analysis of randomized controlled trials.

AIM: To conduct the first-ever systematic review and meta-analysis of randomized controlled trials (RCTs) on the antihemorrhagic utility and safety of tranexamic acid (TXA) versus misoprostol for management (prevention and/or treatment) of postpartum hemorrhage (PPH). METHODS: Six databases were screened from inception until May 2023 and updated in September 2023. The RCTs were assessed for quality according to the Cochrane's risk of bias tool. The endpoints were summarized as mean difference (MD) or risk ratio (RR) with 95% confidence interval (CI) in a random-effects model. RESULTS: Ten RCTs with 2121 patients (TXA = 1061 and misoprostol = 1060) were analyzed. There was no significant difference between TXA and misoprostol groups regarding the mean intraoperative blood loss (n = 9 RCTs, MD = 17.32 ml, 95% CI [-40.43, 75.07], p = 0.56), mean change in hemoglobin (n = 6 RCTs, MD = 0.11 mg/dl, 95% CI [-0.1, 0.31], p = 0.30), mean hospital stay (n = 2 RCTs, MD = -0.3 day, 95% CI [-0.61, 0.01], p = 0.06), blood transfusion rate (n = 4 RCTs, RR = 0.49, 95% CI [0.16, 1.47], p = 0.2), and rate of additional uterotonic agents (n = 4 RCTs, RR = 1.05, 95% CI [0.72, 1.53], p = 0.81). Leave-one-out sensitivity analysis showed robustness of the results, and there was no evidence of publication bias. Regarding safety endpoints, there was no significant difference between both groups regarding the rates of minor side effects, such as diarrhea, fever, nausea, and vomiting. No patient developed thromboembolic events in the TXA group. CONCLUSION: There was no significant antihemorrhagic efficacy between adjunct TXA and misoprostol for the management of PPH. The safety profile was comparable between both agents.

Cardiovascular Mortality in Ovarian Cancer Patients: An Analysis of Patient Characteristics Using the SEER Database.

Background and Objectives: Cardiovascular disease (CVD) is a major contributor to the high mortality rate among individuals with ovarian cancer. Nevertheless, there is limited understanding regarding the specific patient attributes that might impact the risk of CVD in this group. Materials and Methods: A retrospective cohort study was performed using the SEER database to analyze primary ovarian cancer cases from 2000 to 2019. Multivariable logistic regression analysis was employed to identify patient characteristics linked to cardiovascular mortality. Results: The cohort included 41,930 cases of patients who were alive, 54,829 cases of cancer-related deaths, 3003 cases of cardiovascular-related deaths, and 10,238 cases with other causes of death. Poorly differentiated cancer cells and distant metastasis were associated with a higher risk of cardiovascular mortality. Logistic regression analysis identified age, year of diagnosis, race, laterality, and staging as significant risk factors for cardiovascular cause of death. The risk of cardiovascular cause of death was lower in patients aged 31-60 and higher in those aged over 60 years old, and the risk also increased with a later year of diagnosis. Patients who were not white were at a higher risk of cardiovascular cause of death. Additionally, bilateral ovarian cancer and distant staging disease were linked to elevated risks of cardiovascular cause of death. Conclusion: Cardiovascular mortality is a significant concern in ovarian cancer patients, and several patient characteristics are associated with an increased risk. Our study suggests that targeted interventions to improve cardiovascular health in high-risk patients, such as those with comorbidities or an advanced stage at diagnosis, may improve survival in this population.

The ATP Synthase γ Subunit ATPC1 Regulates RNA Editing in Chloroplasts.

RNA editing is the process of modifying RNA molecules by inserting, deleting, or substituting nucleotides. In flowering plants, RNA editing occurs predominantly in RNAs encoded by the organellar genomes of mitochondria and chloroplasts, and the main type of editing involves the substitution of cytidine with uridine at specific sites. Abnormal RNA editing in plants can affect gene expression, organelle function, plant growth, and reproduction. In this study, we report that ATPC1, the gamma subunit of ATP synthase in Arabidopsis chloroplasts, has an unexpected role in the regulation of editing at multiple sites of plastid RNAs. The loss of function of ATPC1 severely arrests chloroplast development, causing a pale-green phenotype and early seedling lethality. Disruption of ATPC1 increases the editing of matK-640, rps12-i-58, atpH-3'UTR-13210, and ycf2-as-91535 sites while decreasing the editing of rpl23-89, rpoA-200, rpoC1-488, and ndhD-2 sites. We further show that ATPC1 participates in RNA editing by interacting with known multiple-site chloroplast RNA editing factors, including MORFs, ORRM1, and OZ1. The transcriptome in the atpc1 mutant is profoundly affected, with a pattern of defective expression of chloroplast development-related genes. These results reveal that the ATP synthase γ subunit ATPC1 is involved in multiple-site RNA editing in Arabidopsis chloroplasts.

Insights on possible interplay between epithelial-mesenchymal transition and T-type voltage gated calcium channels genes in metastatic breast carcinoma.

Breast cancer (BC) is the most common life-threatening malignancy amongst women with high incidence worldwide. In Egypt, it is the most known malignancy amongst females. Epithelial-mesenchymal transition (EMT) participates in breast tumors' invasiveness, and metastasis, but the process is poorly understood. The involvement of voltage-gated calcium channels signaling in EMT has not yet been fully explored. Therefore, the aim of this study was to investigate the possible role of T-type calcium channels in metastasis and EMT among breast cancer patients. The study was carried out on 48 female breast cancer patients who were divided into two groups; metastatic and non-metastatic. qRT-PCR was employed to measure the expression of EMT marker genes (N- cadherin, E-cadherin, Snail, Vimentin and T-type VGCCs genes (CACNA1G, CACNA1H, and CACNA1I). The results of the present study revealed differential expression of the EMT marker genes in blood and tissue of non-metastatic and metastatic breast cancer patients, with a clear tendency for the mesenchymal markers to be significantly elevated in metastatic patients as well as malignant tissues taken from non-metastatic patients as compared to their paired tumor adjacent normal (TAN) tissue. Both CACNA1H and CACNA1I (T-type VGCCs oncogenes) were significantly elevated in blood of metastatic patients when compared to non-metastatic ones. In contrast, CACNA1G (tumor suppressor) exhibited a significant decrease in metastatic patients. The strong correlation between the expression of T-type VGCCs and mesenchymal marker genes in metastatic breast cancer patients casts light on the role of T-type VGCCs in metastasis and their involved in tumor invasiveness.

Isosorbide mononitrate for cervical ripening during labour induction: A systematic review and meta-analysis of 23 randomized controlled trials.

OBJECTIVE: To conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) that evaluated the efficacy and safety of isosorbide mononitrate (IMN) in promoting cervical ripening during labour induction. METHODS: Six major databases were searched from inception until 22 April 2021. The risk of bias of included studies was assessed. Various endpoints (n = 21) were meta-analysed, and the endpoints were pooled as mean differences (MD) or risk ratios (RR) with 95% confidence intervals (CI). RESULTS: In total, 23 RCTs were included in this review, comprising 26 intervention arms and a total of 4305 patients (2210 and 2095 patients were allocated to the IMN and control groups, respectively). Pertaining to obstetric-related maternal outcomes, the pooled analysis showed that admission to delivery time and rate of caesarean delivery were significantly reduced in the IMN group. Moreover, the mean Bishop score and the mean change in Bishop score were significantly increased in the IMN group. Pertaining to drug-related maternal side effect outcomes, the pooled analysis showed that the rates of headache, palpitations, nausea and flushing were significantly lower in the IMN group. Pertaining to neonatal outcomes, the pooled analysis showed no significant difference between the two groups in terms of the rates of neonatal intensive care unit admission, neonatal death, fetal distress, meconium-stained water, Apgar score < 7 at 1 and 5 min, and mean Apgar score at 1 and 5 min. CONCLUSION: IMN correlated with several obstetric-related maternal outcomes. IMN was not associated with adverse neonatal outcomes, but was associated with substantial drug-related maternal side effects.

First report of steroid derivatives isolated from starfish Acanthaster planci with anti-bacterial, anti-cancer and anti-diabetic activities.

Chemical studies on Acanthaster planci have afforded two steroids, 5α-cholesta-24-en-3ß,20ß-diol-23-one (1) and 5α-cholesta-9(11)-en-3ß, 20ß-diol (2). Structures compounds 1 and 2 were determined with the help of spectroscopic studies. Compound 1 showed strong antibacterial activity (21.0 ± 0.06 mm) against P. aeruginosa. Compounds 1 and 2 were also active against human breast carcinoma cells (MCF-7) with LC50 values of 49 ± 1.6 and 57.5 ± 1.5 µg/ml, respectively. This bioactivity was comparable to the currently used anticancer agent, cisplatin (LC50 46 ± 1.1 µg/ml). Compounds 1 and 2 exhibited anti-α-glucosidase activity with IC50 values of 58 ± 0.8 and 55 ± 0.5 µg/ml, respectively, whereas IC50 of Acarbose as a positive control was found to be 36 ± 0.4 µg/ml in our bioassay.

Cytotoxic, chemosensitizing and radiosensitizing effects of curcumin based on thioredoxin system inhibition in breast cancer cells: 2D vs. 3D cell culture system.

Targeting the thioredoxin/thioredoxin reductase (Trx/TrxR) system is a promising strategy to overcome cancer resistance to conventional therapy. The present study investigated the effect of curcumin on the Trx/TrxR system either alone or in combination with chemotherapy, or radiotherapy in human MCF-7 breast cancer cells seeded in 2 and 3D culture systems. Cell viability, thioredoxin reductase 1 (TrxR1) activity, and the genetic expression of Trx, TrxR1, Bcl2 and BAX genes were studied. The findings showed that the mode of culture significantly affected the response of cancer cells to different treatment modalities, as well as their gene expression patterns. Curcumin treatment resulted in a reduction of breast cancer cell proliferation and induction of apoptosis, an effect that may be mediated by manipulating Trx system components, mainly Trx expression, and to a lesser extent TrxR1 expression and concentration. Furthermore, curcumin increased the sensitivity of breast cancer cells to chemotherapy and radiotherapy by reducing Trx and TrxR1 expression levels. Thus, curcumin may have a potential role as a dose-modifying agent that can be used either to sensitize resistant cells to therapy or to reduce the dose of these therapeutic agents.

Effects of structured exercise regime on lipid profile and renal function tests in gestational diabetes mellitus patients:A pilot study.

NOTE OF CONCERN: Article published in Journal of Pakistan Medical Association J Pak Med Assoc.February 2021, No. 2-A,Volume 72 Pages 505-507. This editorial expression of concern serves to notify readers that the Editorial Board has identified discernible weaknesses in the study design, statistical concerns and conclusion drawn regarding this previously published article, titled: "Effects of structured exercise regime on lipid profile and renal function tests in gestational diabetes mellitus patients-A pilot study" J Pak Med Assoc. Vol. 71, No. 2-A, February 2021pages 505-507. The Editorial Board has determined that : 1. The article did not discuss the feasibility of the pilot study, instead attempted to draw inference from the analytical outcomes, which does not allow readers to interpret the desired implications correctly. 2. The statistical methods applied were not at par and did not use the baseline data. The authors did not make full use of the data to add to the scientific weightage of the study, which could have been reported in the text. 3. The conclusion only points towards the positive impacts on serum markers for diabetes mellitus and renal functions. Considering the very small sample size used, this is an unjustified extrapolation. The authors did not attempt to mention the feasibility of the whole process, including participants' willingness, management, and resources that should have been assessed and reported to benefit the planning of the full-scale RCT. The editorial board of JPMA decided to publish this editorial expression of concern when we were made aware of deficiencies in the published article so that future researchers can plan their work on better scientific footings OBJECTIVE: To determine the effects of structured exercise regime on biochemical markers of patients of gestational diabetes mellitus during the third trimester. METHODS: The two-arm pilot study was conducted at the Fauji Foundation Hospital, Rawalpindi, Pakistan, from March to July 2019, and comprised women aged 20-40 years with gestational age >20 weeks who were diagnosed with gestational diabetes mellitus and who were able to do 6min walk test under severity level on the 0-10 Borg scale. The subjects were randomized into two groups using the sealed envelope method. The intervention group received 5 weeks of structured exercise programme. including aerobics, stabilisation and pelvic floor muscle training, while the control group only received postural education. Data was noted at baseline and after intervention, and was analysed using SPSS 20. RESULTS: Of the 16 subjects, there were 8(50%) in each of the two groups. The mean age was 31.5±4.17 years in the interventional group and it was 35.0±6.30 years in the control group. Serum low-density lipoprotein and serum creatinine showed significant differences between the groups (p<0.05), while the rest of markers were non-significant (p>0.05). CONCLUSIONS: Structured exercise regime was found to have a positive effect in reducing serum low-density lipoprotein and serum creatinine levels in gestational diabetes mellitus during the third trimester.

Association of breastfeeding cessation with health-related quality of life in working multiparous women of Rawalpindi and Islamabad.

Breastfeeding rates in Pakistan are the lowest in South Asia. Multiparous working women in Rawalpindi-Islamabad often think if cessation of breastfeeding will affect their and their baby's health. A descriptive cross sectional survey was conducted on 200 multiparous working women to evaluate the association between cessation of breastfeeding and health-related quality of life in multiparous working women and to determine the common reasons of breastfeeding cessation. A modified SF-36 QOL questionnaire was used. The mothers who breastfed their babies for less than or up to six months reported their general health worse at the time of study than one year ago, which accounts for 34(68%) of the entire data, 42(21%) women ceased to breastfeed their babies due to less milk production and 31 (15.5%) women due to the nature of their job. Chi-Square test showed that there is a significant association (i.e. p-value < 0.001) between health-related quality of life and early breastfeeding cessation.

Electrochemical assessment of laser-treated titanium alloy used for dental applications at acidic pH condition (in vitro study).

BACKGROUND: Titanium alloys are widely used in dental applications as they have good mechanical and biological properties. Implant failure is more likely to occur in inflammatory diseases related to acidic pH. The aim of the present study was to assess the effect of erbium chromium-doped yttrium-scandium-gallium-garnet 2780 nm laser surface treatment on the electrochemical behavior of titanium alloy (Ti-6Al-4V) at acidic pH. MATERIALS AND METHODS: In this in vitro study, a total of 20 discs of titanium alloy (Ti-6Al-4V) were used. First group, ten discs were irradiated with Er, Cr: YSGG laser which was operating in a normal room atmosphere and temperature at power 2W for 20 s at a constant distance of 0.5-1 mm with the laser system. The second group, ten discs untreated. The electrochemical behavior for both groups was investigated in simulated body fluid at pH 5.20 for up to 864 h at 192, 360, 696, and 864 h intervals using potentiodynamic polarization test and electrochemical impedance spectroscopy to evaluate the corrosion resistance. RESULTS: Laser-treated Ti-6Al-4V showed higher corrosion resistance at pH 5.20 compared to the untreated alloy. Immersion time affected the electrochemical behavior. CONCLUSION: Er, Cr: YSGG laser could improve the corrosion resistance of Ti-6Al-4V at acidic pH.

Assessments of Bone Height Loss in Telescopic Mandibular Implant-Retained Overdentures Retained by Two and Four End - Osseous Implants: A Randomized Clinical Trial.

AIM: This randomized clinical study aimed to assess bone height loss when using mandibular implant overdentures retained by two and four endosseous implants using the telescopic attachments. METHODS: Twelve completely edentulous patients were randomly allocated so that six patients were treated by telescopic implant overdenture retained by two implants (group A) and six patients were treated with overdentures retained by four implants (group B). Digital radiographic evaluation of bone height using Digora was made starting at the functional loading day followed by time intervals of 12 months. RESULTS: No implant loss during the healing period or after functional loading. Radiographic evaluation revealed a statistically significant difference was found between (Group A) and (Group B) were (p < 0.001). CONCLUSION: For bone loss, widely distributed four intraforaminal implants revealed more bone preservation than only two implants when using the telescopic attachments to support and retain an over dentures taking in consideration the type of the attachment will be used.

Prediction and Staging of Hepatic Fibrosis in Children with Hepatitis C Virus: A Machine Learning Approach / 대한의료정보학회지

OBJECTIVES: The aim of this study is to develop an intelligent diagnostic system utilizing machine learning for data cleansing, then build an intelligent model and obtain new cutoff values for APRI (aspartate aminotransferase-to-platelet ratio) and FIB-4 (fibrosis score) for the prediction and staging of fibrosis in children with chronic hepatitis C (CHC). METHODS: Random forest (RF) was utilized in this study for data cleansing; then, prediction and staging of fibrosis, APRI and FIB-4 scores and their areas under the ROC curve (AUC) have been obtained on the cleaned dataset. A cohort of 166 Egyptian children with CHC was studied. RESULTS: RF, APRI, and FIB-4 achieved high AUCs; where APRI had AUCs of 0.78, 0.816, and 0.77; FIB-4 had AUCs of 0.74, 0.828, and 0.78; and RF had AUCs of 0.903, 0.894, and 0.822, for the prediction of any type of fibrosis, advanced fibrosis, and differentiating between mild and advanced fibrosis, respectively. CONCLUSIONS: Machine learning is a valuable addition to non-invasive methods of liver fibrosis prediction and staging in pediatrics. Furthermore, the obtained cutoff values for APRI and FIB-4 showed good performance and are consistent with some previously obtained cutoff values. There was some agreement between the predictions of RF, APRI and FIB-4 for the prediction and staging of fibrosis.

Nine months versus 12 months of adjuvant trastuzumab for patients with HER2-positive breast cancer

PURPOSE: This study aimed to compare the results of treatment with adjuvant trastuzumab for 9 months versus 12 months in human epidermal growth factor 2 (HER2)-positive breast cancer patients. The primary endpoint was disease-free survival. Secondary endpoints included cardiac safety, tolerability, and overall survival.METHODS: The study included 60 non-metastatic HER2-positive breast cancer patients. All study patients underwent surgery, received adjuvant chemotherapy, radiotherapy and hormonal therapy if indicated. Thirty patients were randomized in each group. Group I patients received adjuvant trastuzumab for 12 months, while group II patients received adjuvant trastuzumab for 9 months. Patients were assessed by clinical examination and Echocardiography during treatment.RESULTS: After median follow-up of 12 months, 90% of the patients in group I were disease free and 83.3% of patients in group II were disease free (P=0.402). All studied population in both groups I and II were alive at the end of the 1-year follow-up period after the completion of adjuvant trastuzumab treatment thus overall survival is 100%.CONCLUSION: Trastuzumab is tolerable and its side effects are reversible. Nine months of adjuvant trastuzumab treatment is more cost effective than the standard 12 months.

Changing cultural attitudes towards female genital cutting.

As globalization brings people with incompatible attitudes into contact, cultural conflicts inevitably arise. Little is known about how to mitigate conflict and about how the conflicts that occur can shape the cultural evolution of the groups involved. Female genital cutting is a prominent example. Governments and international agencies have promoted the abandonment of cutting for decades, but the practice remains widespread with associated health risks for millions of girls and women. In their efforts to end cutting, international agents have often adopted the view that cutting is locally pervasive and entrenched. This implies the need to introduce values and expectations from outside the local culture. Members of the target society may view such interventions as unwelcome intrusions, and campaigns promoting abandonment have sometimes led to backlash as they struggle to reconcile cultural tolerance with the conviction that cutting violates universal human rights. Cutting, however, is not necessarily locally pervasive and entrenched. We designed experiments on cultural change that exploited the existence of conflicting attitudes within cutting societies. We produced four entertaining movies that served as experimental treatments in two experiments in Sudan, and we developed an implicit association test to unobtrusively measure attitudes about cutting. The movies depart from the view that cutting is locally pervasive by dramatizing members of an extended family as they confront each other with divergent views about whether the family should continue cutting. The movies significantly improved attitudes towards girls who remain uncut, with one in particular having a relatively persistent effect. These results show that using entertainment to dramatize locally discordant views can provide a basis for applied cultural evolution without accentuating intercultural divisions.

Increased levels of type 1 interferon in a type 1 diabetic mouse model induce the elimination of B cells from the periphery by apoptosis and increase their retention in the spleen.

BACKGROUND: The autoimmune disease type 1 diabetes mellitus (T1D) is associated with a defect in the immune response, which increases susceptibility to infection. We recently demonstrated that prolonged elevated levels of type 1 interferon (IFN) induce lymphocyte exhaustion during T1D. AIMS: In the present study, we further investigated the effect of blocking the type I IFN receptor signaling pathway on diabetic dyslipidemia, in which an abnormal lipid profile leads to the exhaustion of B cells and alteration of their distribution and functions. METHODS: T1D was induced in a mouse model by an intraperitoneal injection of a single dose (60 mg/kg) of streptozotocin (STZ). Three groups of mice were examined: a non-diabetic control group, a diabetic group and a diabetic group treated with an anti-IFN (alpha, beta and omega) receptor 1 (IFNAR1) blocking antibody to block type I IFN signaling. RESULTS: We observed that induction of T1D was accompanied by a marked destruction of ß cells and a reduction in the insulin levels in the diabetic group. Diabetic mice exhibited many changes, including alterations in their lipid profiles, expansion of splenic B cells, increased caspase-3, -8 and -9 activity, and apoptosis in peripheral B cells. Blocking type 1 IFN signaling in diabetic mice significantly returned the insulin and lipid profiles to normal levels, subsequently restored the B cell distribution, and rescued the peripheral B cells from apoptosis. CONCLUSION: Our data suggest the potential role of type I IFN in mediating diabetic dyslipidemia and an exhausted state of B cells during T1D.