Correction: Leppäniemi et al. Nutrition Profile for Countries of the Eastern Mediterranean Region with Different Income Levels: An Analytical Review. Children 2023, 10, 236.

In the original publication [...].

Bioremoval of tannins and heavy metals using immobilized tannase and biomass of Aspergillus glaucus.

BACKGROUND: The presence of inorganic pollutants and heavy metals in industrial effluents has become a serious threat and environmental issues. Fungi have a remarkable ability to exclude heavy metals from wastewater through biosorption in eco-friendly way. Tannase plays an important role in bioconversion of tannin, a major constituent of tannery effluent, to gallic acid which has great pharmaceutical applications. Therefore, the aim of the current study was to exploit the potential of tannase from Aspergillus glaucus and fungal biomass waste for the bioremediation of heavy metals and tannin. RESULTS: Tannase from A. glaucus was partially purified 4.8-fold by ammonium sulfate precipitation (80%). The enzyme was optimally active at pH 5.0 and 40 °C and stable at this temperature for 1 h. Tannase showed high stability at different physiological conditions, displayed about 50% of its activity at 60 °C and pH range 5.0-6.0. Immobilization of tannase was carried out using methods such. as entrapment in Na-alginate and covalent binding to chitosan. The effects of Na-alginate concentrations on the beads formation and enzyme immobilization revealed that maximum immobilization efficiency (75%) was obtained with 3% Na-alginate. A potential reusability of the immobilized enzyme was showed through keeping 70% of its relative activity up to the fourth cycle. The best bioconversion efficiency of tannic acid to gallic acid by immobilized tannase was at 40 °C with tannic acid concentration up to 50 g/l. Moreover, bioremediation of heavy metal (Cr3+, Pb2+, Cu2+, Fe3+, and Mn2+) from aqueous solution using A. glaucus biomass waste was achieved with uptake percentage of (37.20, 60.30, 55.27, 79.03 and 21.13 respectively). The biomass was successfully used repeatedly for removing Cr3+ after using desorbing agent (0.1 N HCl) for three cycles. CONCLUSION: These results shed the light on the potential use of tannase from locally isolated A. glaucus in the bioremediation of industrial tanneries contained heavy metals and tannin.

Prevalence of vitamin D deficiency and the effect of vitamin D3 supplementation on response to anti-tuberculosis therapy in patients with extrapulmonary tuberculosis.

BACKGROUND: We aimed to assess serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations in extrapulmonary tuberculosis (EPTB) patients and to evaluate the effect of vitamin D3 supplementation on their treatment course. METHODS: Serum 25(OH)D3concentrations were measured in 47 newly diagnosed EPTB patients and 42 controls. Vitamin D-deficient EPTB patients were randomly assigned to receive 50,000 IU of vitamin D3 (cholecalciferol) orally once a week for 6 weeks (total 300,000 IU), followed by maintenance doses of 1000 IU a day besides anti-TB drugs or the first line anti-TB treatment only. Follow up serum 25(OH)D3 concentrations were measured after 3 months of starting vitamin D3 supplementation. Both groups were evaluated for clinical, laboratory, and radiological outcomes after treatment. RESULTS: Serum 25(OH)D3 concentrations were significantly lower among TB cases (17.1 ± 5.5 nmol/L) compared to healthy controls (51.8 ± 27.3 nmol/L), and vitamin D deficiency was observed in all EPTB patients (n = 47). Patients in VD3 supplementation group had significantly higher weight gain and serum albumin level at 2 months and end of treatment, higher hemoglobin concentration at the end of treatment, significantly lower CRP and ESR at 2 months and at the end of treatment. In cases with TB pleurisy, a significant higher rate of full resolution of pleural fluid after 6 months of anti-TB treatment and shorter treatment duration were noted compared to the other group. CONCLUSIONS: Vitamin D deficiency is prevalent in EPTB patients, in whom, vitamin D supplementation is a useful adjunctive therapy to anti-TB drugs and improves treatment course.

Histopathological Profile of Different Breast Lesions: A Single-Center Observational Study.

OBJECTIVE: To describe the histopathological pattern of different breast lesions among tissue specimens sent to our laboratory. METHOD: A record-based study using a retrospective review of 255 histologically diagnosed breast biopsy reports in the histopathology department of authors from December 2016 to November 2021 was conducted. The specimens were collected from core biopsy, lumpectomy, and mastectomy. All data obtained were analyzed using the Statistical Package for the Social Sciences (SPSS) version 28 (IBM SPSS Statistics, Armonk, NY). Then, the findings were presented using text, tables, and charts. RESULT: A total of 255 breast lesions were analyzed in this study. Most of the cases were benign (58.8%), followed by inflammatory lesions (21.6%), and malignant (19.6%). Fibroadenoma was the most prevalent benign lesion (36.7%), and most of the patients (70.9%) were in the age group of 20-39 years old. The most common inflammatory lesion was granulomatous mastitis (56.4%), and most of the cases were diagnosed in the age group of 30-39 years old. Invasive ductal carcinoma (IDC) was the most encountered histological type of carcinoma (62%). Of the malignant cases, 52% were diagnosed before the age of 50 years. Among these 50 cases, grade 2 was the most prevalent one (46%). CONCLUSION: Benign breast lesions are more common than malignant breast lesions, and fibroadenoma is the most common benign subtype. Granulomatous mastitis is the most prevalent inflammatory breast lesion. About two-thirds of malignant cases are non-Arab. Invasive ductal carcinoma with no special type (NST) is the most common malignant subtype.

The use of urodynamic to assess the mechanism of incontinence in patients with Yang-Monti based catheterizable cutaneous stomas.

OBJECTIVE: To analyze the static and dynamic urodynamic parameters of reservoirs and continent conduits in continent cutaneous urinary diversion with catheterizable stoma. MATERIALS AND METHODS: 76 patients had augmented ileocystoplasty or continent urinary diversion with catheterizable urinary stoma based on Mitrofanoff principle and Yang-Monti procedure using subserous tunnel as continence mechanism. They were followed up for at least 6 months post-operatively for continence through stoma and divided into two groups (continents vs non-continent) according to stomal continence. Both groups had urodynamic assessment performed via the stoma to assess reservoir capacity, pressure and contractions, efferent limb functional length, reservoir overactivity, static and dynamic maximal closure pressures and leak point pressure. RESULTS: Continence rate was 87%. Continent group included 66 patients and incontinent group included 10 patients. In both groups at rest, the reservoir pressure after filling did not exceed 25 cm H2O. During peristaltic contraction, the pressure did not exceed 30 cm H2O and the duct remained continent. After Valsalva maneuver, the reservoir pressure increased up to 34 (+ 7.4) cm H2O and leakage occur in 10 patients (13%). Reservoir (wall) overactivity was recorded in 54 patients, with insignificant rise in intraluminal pressure during the contractions. In both groups, the efferent tract closing pressure was always higher than the reservoir pressure. The mean of maximal closing pressure at Valsalva was 82.5 (+ 4.18) cm H2O in the continent group and 61.66 (+ 8.16) cm H2O in the incontinent group. The mean functional length of the conduit was 4.95 + 1.62 in the continent group and 2.80 + 1.50 cm in the incontinent group. CONCLUSIONS: Urodynamic evaluation of continent catheterizable cutaneous stoma after Yang-Monti procedure has a practical significance. Functional length of the conduit seems to be the most influential factor for continence reflecting static & dynamic maximal closure pressure. Higher conduit closing pressure is associated with better continence. Contractions of the pouch and peristaltic contraction of the conduit has no effect on continence mechanism.

Navigating the future of guided dental implantology: A scoping review.

BACKGROUND: The aim of this scoping review was to understand the development of robotics and its accuracy in placing dental implants when compared to other forms of guided surgery. METHODS: An electronic search was conducted on the electronic databases of PubMed, Cochrane, and Science direct with the following queries: ((robotics) AND (dental implant)) AND (accuracy). The search timeline was between 2017 and 2022. RESULTS: A total of 54 articles were screened for title and abstract, of which 16 were deemed eligible for inclusion. Thirty-one articles were excluded mainly because they were out of topic (not relevant) or not in English. In total, 16 articles were included for analysis. CONCLUSIONS: This review thoroughly analyses 5 years of literature concerning the evolution of robotics in dental implant surgery, underscoring the necessity for additional research on nascent technologies reported and a comparative study with static and dynamic systems for clinical efficacy evaluation.

Modified McKissock's Breast Reduction Technique: A Case Series and Description of Our Technique Modification.

Background: The modified McKissock breast reduction technique uses upper and lower vascular pedicles to reduce breast size and reshape the breasts. This technique has gained significant interest in recent years because of its potential to minimize surgical complications. The current study aims to report our experience and results with our refined version of the McKissock technique. Methods: We conducted a prospective cohort study on patients with breast hypertrophy between 2022 and 2023 to evaluate the modified McKissock breast reduction technique. Two main alterations were made to the original McKissock technique. First, the superior pedicle was modified to create a superomedial pedicle. Second, the inferior pedicle was thinned to form a dermoseptal pedicle with a 4 cm wide base. Results: A total of 13 patients underwent surgery using the modified McKissock breast reduction technique. The average age of the patients was 37.2 years. For the right breast, the weight of tissue resected during reduction ranged from 189 g to 695 g (average 379 g). For the left breast, the resection weight range was 160 g to 608 g (average 370 g). There were no complications except one patient who developed partial nipple necrosis on the left side. All patients expressed satisfaction with the outcomes. Conclusion: Our modified McKissock breast reduction technique shows promise as a method for reducing breast size. It offers several potential advantages, including improved preservation of the nipple and areola complex, more precise breast shaping, contouring capabilities, and reduced risk of complications. Although the early results of this technique are encouraging, further research is required to evaluate its long-term benefits and risks fully.

Accuracy of Ultrasound in the Prediction of the FIGO Classification of Placenta Accreta Spectrum.

OBJECTIVES: To evaluate the accuracy of greyscale ultrasound (US) and colour Doppler detecting placenta accreta spectrum (PAS) based on the newly recommended International Federation of Obstetrics and Gynaecology (FIGO) grading system. METHODS: This prospective study was conducted on women diagnosed with placenta previa or low-lying placenta involving the anterior uterine wall and associated with PAS as identified by the US. Transabdominal and transvaginal greyscale US was performed on admission between 34 and 36 weeks of gestation and compared to clinical grading and histopathological examination after cesarean hysterectomy. RESULTS: In total, 36 pregnant females who underwent a cesarean hysterectomy due to placenta previa complicated by PAS were included in this study. All patients had a history of previous cesarean deliveries, ranging from 1 to 5 deliveries. The US has an overall sensitivity of 33%, 55%, and 84.62%, and specificity of 100%, 75%, and 60% in detecting the 3 degrees of PAS, respectively. US cannot differentiate between the different subtypes of PAS grade 3 (a, b, and c). CONCLUSION: The overall US evaluation was highly significant in predicting the FIGO diagnosis of PAS; however, all ultrasonographic signs were equally relevant in diagnosing grade 1 and/or 2 PAS and were inaccurate in differing the subtypes of PAS grade 3.

Bridging responses to a human telomerase reverse transcriptase-based peptide cancer vaccine candidate in a mechanism-based model.

Therapeutic cancer vaccines are novel immuno-therapeutics, aiming to improve clinical outcomes with other immunotherapies. However, obstacles to their successful clinical development remain, which model-informed drug development approaches may address. UV1 is a telomerase based therapeutic cancer vaccine candidate being investigated in phase I clinical trials for multiple indications. We developed a mechanism-based model structure, using a nonlinear mixed-effects modeling techniques, based on longitudinal tumor sizes (sum of the longest diameters, SLD), UV1-specific immunological assessment (stimulation index, SI) and overall survival (OS) data obtained from a UV1 phase I trial including non-small cell lung cancer (NSCLC) patients and a phase I/IIa trial including malignant melanoma (MM) patients. The final structure comprised a mechanistic tumor growth dynamics (TGD) model, a model describing the probability of observing a UV1-specific immune response (SI ≥ 3) and a time-to-event model for OS. The mechanistic TGD model accounted for the interplay between the vaccine peptides, immune system and tumor. The model-predicted UV1-specific effector CD4+ T cells induced tumor shrinkage with half-lives of 103 and 154 days in NSCLC and MM patients, respectively. The probability of observing a UV1-specific immune response was mainly driven by the model-predicted UV1-specific effector and memory CD4+ T cells. A high baseline SLD and a high relative increase from nadir were identified as main predictors for a reduced OS in NSCLC and MM patients, respectively. Our model predictions highlighted that additional maintenance doses, i.e. UV1 administration for longer periods, may result in more sustained tumor size shrinkage.

Imbalance of Follicular Helper and Follicular Regulatory T Cells in Chronic Rhinosinusitis with Nasal Polyps.

OBJECTIVE: Data regarding the imbalance in follicular helper T (Tfh) and follicular regulatory T (Tfr) cell responses in patients having chronic rhinosinusitis with nasal polyps (CRSwNP) is so far limited. Thus, we aimed to assess the changes in circulating Tfh and Tfr in CRSwNP patients. METHODS: This case-control study included 21 patients having CRSwNP and 20 age and sex-matched healthy blood donors as a control group. Lund-Mackay staging system was used for radiologic scoring of chronic rhinosinusitis. Two milliliters of peripheral blood samples were collected from all participants into EDTA-containing vacutainer tubes to assess the levels of Tfh and Tfr cells using flow cytometry. RESULTS: Patients having CRSwNP did not show significant differences in the percentages of CD4+ T cells and total CD4+CXCR5+ T cells from healthy controls. Meanwhile, levels of both activated circulating Tfh and Tfr showed a marked rise in patients than controls. In addition, a positive correlation was observed between the levels of both activated Tfh and Tfr cells. CONCLUSION: An imbalance in circulating Tfh/Tfr levels was detected in patients having CRSwNP. A significant rise in the levels of Tfh and Tfr was detected in patients proposing a possible role of this imbalance in disease pathogenesis.

Evaluation of HHLA2 and CD8 Immunohistochemical Expression in Colorectal Carcinoma and Their Prognostic Significance.

BACKGROUND: Colorectal carcinoma (CRC) is the third most common malignancy worldwide. Human endogenous retrovirus H long terminal repeat-associating protein 2 (HHLA2) is a novel immune checkpoint molecule. The association between HHLA2 expression and clinicopathological features and its prognostic significance in CRC patients are still controversial. The aim of this study is to evaluate the prognostic value of immunohistochemical (IHC) expression of HHLA2 and CD8 in CRC. MATERIAL AND METHODS: This retrospective study included 134 cases diagnosed with primary CRC at the Gastrointestinal Surgery Center (GISC) department, Mansoura Faculty of Medicine, during the period from December 2014 to December 2018. Clinicopathological and survival data were collected. IHC for HHLA2 and CD8 was performed, and they were correlated with clinicopathological parameters and patient prognosis. RESULTS: Among 134 CRC cases, high HHLA2 expression was detected in 73 (54.5%). High HHLA2 expression was significantly related to the depth of invasion (P = 0.005*), lymph node metastasis (P = 0.01*), tumor stage )P = 0.002*), and distant recurrence )P = 0.012*). Multivariate analysis spotted HHLA2 high expression as an independent prognostic predictor for OS in CRC (P = 0.03*) and DFS (P = 0.008*). CD8 shows a significant correlation with tumor infiltrating lymphocytes (TILs) (P ≤ 0.001*), absence of metastasis ((P = 0.029*), absence of tumor deposits (P=0.014*). However, CD8 shows no significant association with survival or HHLA2. CONCLUSION: HHLA2 is an independent prognostic factor for the overall survival and disease free survival of CRC patients and can predict poor prognosis in CRC patients.

Molecular characterization of tetracycline and vancomycin-resistant Enterococcus faecium isolates from healthy dogs in Egypt: a public health threat.

BACKGROUND: Vancomycin-resistant enterococci (VRE) are among the most common causative pathogens for nosocomial infections worldwide. Moreover, strains of VRE have been isolated from several domestic livestock in Egypt. METHODS: This study examined if healthy dogs are a potential source of VRE infection by isolating and characterizing Enterococcus faecium strains from stool samples on a morphological basis and biochemical activities. Subsequently, it was confirmed by genotypic characterization using polymerase chain reaction (PCR), followed by the detection of antibiotic resistance genes, virulence determinants, and genes contributing to enterocin production by PCR. Furthermore, the phylogenetic relationships among vanB and tetL genes were analyzed. RESULTS: All ten fecal samples were identified as E. faecium and confirmed by PCR. In addition, 90% of the isolates tested were positive for the virulence genes gelE and esp, and all the isolates tested were positive for the antibiotic resistance genes tetL and vanB. Only three of the five enterocin genes examined were detected. Ent As-48, bacteriocin 31, and Ent L50 were identified in 100%, 80%, and 60% of the samples, respectively. CONCLUSION: Dogs should be regarded as a reservoir of E. faecium that carries vancomycin resistance and virulence determinants that may affect public health in Egypt, considering a "One Health" task force approach to restrict their spread.

Exploring the prevalence of Human Papillomavirus (HPV) genotypes in PAP smear samples of women in northern region of United Arab Emirates (UAE): HPV Direct Flow CHIP system-based pilot study.

OBJECTIVE: The aim of this study was to explore the prevalence of low and high-risk HPV genotypes in PAP smear samples of women in northern region of the UAE using HPV direct flow CHIP method. METHODS: A cross-sectional retrospective study was conducted between September 2021 to April 2022. A total of 104 liquid-based cervical cytology samples were obtained from women aged 20-59 years attending the Gynaecology out-patient department of Thumbay University Hospital and other hospitals of Northern Emirates of UAE, processed for the routine cytological examination to identify and differentiate morphological changes of the PAP smear samples. HPV genotyping was performed using HPV direct flow CHIP method. RESULTS: In total, 112 HPV genotypes were detected in 63 women (60.57%) included 18 abnormal cytological and 45 normal epithelial samples. 63 LR and 49 HR HPV genotypes were identified in all the 63 positive samples. Highest rate of infection with multiple LR and HR HPV genotypes were detected in women aged 40-49 years (25.9%) and 20-29 years (23.5%). Infection by HPV6 (13.46%), HPV11 (9.61%), HPV16 (9.61%), HPV62/81 (7.69%) and HPV45 (7.69%) were the most common genotypes. A moderate increase than expected incidence of HPV45 and 62/81 (7.69%) were detected. Co-infection with multiple low and high-risk genotypes is present in 20.2% cases; in that, HPV6 (15.9%) was the most common followed by HPV62/81 (12.7%) and HPV16 (11.11%). The prevalence of HPV18 was found to be 1.6%. CONCLUSION: The genotypes 6, 45, 16, 11, 67, 62/81 were the most common HPV infections in the women between the age group of 21 and 59-years-old. A moderate increase of HPV45, 62/81 and much less prevalence of HPV18 were detected in the study population. 43.27% of the normal epithelia were positive to different low and high-risk HPV genotypes. This finding highlights the importance of molecular genotyping of HPV to emphasize the cervical screening triage.

A Markov model of fibrosis development in nonalcoholic fatty liver disease predicts fibrosis progression in clinical cohorts.

Disease progression in nonalcoholic steatohepatitis (NASH) is highly heterogenous and remains poorly understood. Fibrosis stage is currently the best predictor for development of end-stage liver disease and mortality. Better understanding and quantifying the impact of factors affecting NASH and fibrosis is essential to inform a clinical study design. We developed a population Markov model to describe the transition probability between fibrosis stages and mortality using a unique clinical nonalcoholic fatty liver disease cohort with serial biopsies over 3 decades. We evaluated covariate effects on all model parameters and performed clinical trial simulations to predict the fibrosis progression rate for external clinical cohorts. All parameters were estimated with good precision. Age and diagnosis of type 2 diabetes (T2D) were found to be significant predictors in the model. Increase in hepatic steatosis between visits was the most important predictor for progression of fibrosis. Fibrosis progression rate (FPR) was twofold higher for fibrosis stages 0 and 1 (F0-1) compared to fibrosis stage 2 and 3 (F2-3). A twofold increase in FPR was observed for T2D. A two-point steatosis worsening increased the FPR 11-fold. Predicted fibrosis progression was in good agreement with data from external clinical cohorts. Our fibrosis progression model shows that patient selection, particularly initial fibrosis stage distribution, can significantly impact fibrosis progression and as such the window for assessing drug efficacy in clinical trials. Our work highlights the increase in hepatic steatosis as the most important factor in increasing FPR, emphasizing the importance of well-defined lifestyle advise for reducing variability in NASH progression during clinical trials.

Phenotypic diagnosis and genotypic identification of Bacillus cereus causing subclinical mastitis in cows.

Background and Aims: Bovine mastitis is a disease that affects dairy cows and impacts the global dairy industry. Bacillus spp. can infect the mammary gland during lactation, intramammary treatment, or dry cow therapy. This study aimed to isolate and identify Bacillus spp. in raw milk samples from cows with subclinical mastitis from dairy farms in Beheira, Giza, Alexandria, and Menoufia Governorate, Egypt. We also investigated their antibiotic sensitivity and detected the enterotoxigenic and antibiotic resistance genes. Materials and Methods: A total of 262 milk samples (15-20 ml each) were examined microscopically, biochemically, and phenotypically. A polymerase chain reaction was used for genotypic identification and detecting antibiotic-resistance and enterotoxigenic genes. Antibiotic sensitivity was tested using the agar well diffusion test. Results: Bacillus cereus was identified in 47.7% of samples. Nhe and hblD enterotoxin genes were found in 93.64% (103/110) and 91.82% (101/110) of the samples, respectively. Tetracycline and ß-lactam antibiotic-resistance genes were present in 0% (0/110) and 98.18% (108/110), respectively, of the samples. All isolates were resistant to cefepime, cefixime, and oxacillin, while they were susceptible to amoxicillin-clavulanic, chloramphenicol, ampicillin/sulbactam, and levofloxacin. Conclusion: These results highlight the need to promote awareness regarding B. cereus, the most common pathogen causing mastitis in Egyptian dairy cows. We also emphasized that antibiotic misuse during mastitis is a potential public health threat.

Implementation strategies, facilitators, and barriers to scaling up and sustaining post pregnancy family planning, a mixed-methods systematic review.

BACKGROUND: Post pregnancy family planning includes both postpartum and post-abortion periods. Post pregnancy women remain one of the most vulnerable groups with high unmet need for family planning. This review aimed to describe and assess the quality of the evidence on implementation strategies, facilitators, and barriers to scaling up and sustaining post pregnancy family planning. METHODS: Electronic bibliographic databases (MEDLINE, PubMed, Scopus, the Cochrane Library, and Global Index Medicus) were searched from inception to October 2022 for primary quantitative, qualitative, and mixed method reports on scaling up post pregnancy family planning. Abstracts, titles, and full-text papers were assessed according to the inclusion criteria to select studies regardless of country, language, publication status, or methodological limitations. Data were extracted and methodological quality assessed using the Mixed Methods Appraisal Tool. The convergent integrated approach and a deductive thematic synthesis were used to identify themes and sub-themes of strategies to scale up post pregnancy family planning. The health system building blocks were used to summarize barriers and facilitators. GRADE-CERQual was used to assess our confidence in the findings. RESULTS: Twenty-nine reports (published 2005-2022) were included: 19 quantitative, 7 qualitative, and 3 mixed methods. Seven were from high-income countries, and twenty-two from LMIC settings. Sixty percent of studies had an unclear risk of bias. The included reports used either separate or bundled strategies for scaling-up post pregnancy family planning. These included strategies for healthcare infrastructure, policy and regulation, financing, human resource, and people at the point of care. Strategies that target the point of care (women and / or their partners) contributed to 89.66% (26/29) of the reports either independently or as part of a bundle. Point of care strategies increase adoption and coverage of post pregnancy contraceptive methods. CONCLUSION: Post pregnancy family planning scaling up strategies, representing a range of styles and settings, were associated with improved post pregnancy contraceptive use. Factors that influence the success of implementing these strategies include issues related to counselling, integration in postnatal or post-abortion care, and religious and social norms. TRIAL REGISTRATION: Center for Open Science, OSF.IO/EDAKM.

Family planning could prevent one third of maternal deaths by allowing women to delay motherhood, avoid unintended pregnancies and subsequent abortions. Post pregnancy family planning includes both postpartum and post-abortion periods. Post pregnancy women remain one of the most vulnerable groups with high unmet need for family planning. Scaling up post pregnancy family planning is essential for achieving universal access to reproductive health-care services. Reports of strategies to scale up post pregnancy family planning were systematically reviewed and summarized. These included strategies for healthcare infrastructure, policy and regulation, financing, human resource, and people at the point of care. Strategies that target the point of care (women and/or their partners) contributed to 89.66% (26/29) of the reports either independently or as part of a bundle. Point of care strategies increase adoption and coverage of post pregnancy contraceptive methods. Certain factors influence the success of implementing these strategies, including issues related to counselling, integration in postnatal or post-abortion care, and religious and social norms.

Assessment of ibrutinib scheduling on leukocyte, lymph node size and blood pressure dynamics in chronic lymphocytic leukemia through pharmacokinetic-pharmacodynamic models.

Ibrutinib is a Bruton tyrosine kinase (Btk) inhibitor for treating chronic lymphocytic leukemia (CLL). It has also been associated with hypertension. The optimal dosing schedule for mitigating this adverse effect is currently under discussion. A quantification of relationships between systemic ibrutinib exposure and efficacy (i.e., leukocyte count and sum of the product of perpendicular diameters [SPD] of lymph nodes) and hypertension toxicity (i.e., blood pressure), and their association with overall survival is needed. Here, we present a semi-mechanistic pharmacokinetic-pharmacodynamic modeling framework to characterize such relationships and facilitate dose optimization. Data from a phase Ib/II study were used, including ibrutinib plasma concentrations to derive daily 0-24-h area under the concentration-time curve, leukocyte count, SPD, survival, and blood pressure measurements. A nonlinear mixed effects modeling approach was applied, considering ibrutinib's pharmacological action and CLL cell dynamics. The final framework included (i) an integrated model for SPD and leukocytes consisting of four CLL cell subpopulations with ibrutinib inhibiting phosphorylated Btk production, (ii) a turnover model in which ibrutinib stimulates an increase in blood pressure, and (iii) a competing risk model for dropout and death. Simulations predicted that the approved dosing schedule had a slightly higher efficacy (24-month, progression-free survival [PFS] 98%) than de-escalation schedules (24-month, average PFS ≈ 97%); the latter had, on average, ≈20% lower proportions of patients with hypertension. The developed modeling framework offers an improved understanding of the relationships among ibrutinib exposure, efficacy and toxicity biomarkers. This framework can serve as a platform to assess dosing schedules in a biologically plausible manner.

Body Mass Index As A Prognostic Factor In HER-2 Positive Early Breast Cancer Patients And Its Effect On Duration Of Treatment With Trastuzumab: A Retrospective Study.

Objectives: To evaluate prognostic value of body mass index in human epidermal growth factor receptor 2-positive early breast cancer, and to evaluate the duration of trastuzumab administration. Method: The retrospective study was conducted from March 2020 to December 2021 at Kafrelsheikh University Hospital and Zagazig University Hospital, Egypt, and comprised data of women diagnosed between 2015 and 2017 with stage III human epidermal growth factor receptor 2-positivebreast cancer, who were treated with adjuvant chemotherapy and trastuzumab for a year. Body massindex had been calculated at the time of diagnosis, and data was divided into 3 groups: average weight group A, overweight group B and obese group C. Disease-free survival, distant disease-free survival and overall survival were estimated for all the three groups. Data was analysed using SPSS 26. RESULTS: The mean age of 160 cases was 44.99±11.35 years(range: 25-66 years). There were 93(58.1) postmenopausal women, 60(37.5%) had positive family history and 128 (80%) underwent modified radical mastectomy. There were 60(37.5%) patients in group A, 49(30.6%) in group B and 51(31.9%) in group C. There was significant association of body mass index with disease-free survival and distant disease-free survival (p<0.05), but not with overall survival (p>0.05). Significant difference was noted between body mass index and duration of trastuzumab (p<0.001). CONCLUSIONS: Body massindex wasfound to be an independent prognostic factor for human epidermal growth factor receptor 2-positiveearly breast cancer.

Retention of zirconia crowns to titanium bases with straight versus angled screw access channels: an invitro study.

BACKGROUND: The aim of this study was to assess the impact of abutments with angled screw access channel on the retention of zirconia crowns. METHODS: Seven implant replicas were inserted in epoxy resin blocks. Fourteen zirconia crowns for central incisor tooth were digitally fabricated and cemented to titanium bases (Ti-bases) with resin cement. Titanium bases were categorized into 2 groups (n = 7). Control group (Group STA) included straight screw access channel abutments. Study group (Group ASC) included angled screw access channel abutments. Following aging (5 °C-55 °C, 60 s; 250,000 cycles, 100 N, 1.67 Hz), the pull-off forces (N) were recorded by using retention test (1 mm/min). Types of failure were defined as (Type 1; Adhesive failure when luting agent predominantly remained on the Ti-base surface (> 90%); Type 2; Cohesive failure when luting agent remained on both Ti-base and crown surfaces; and Type 3; Adhesive failure when luting agent predominantly remained on the crown (> 90%). Statistical analysis was conducted by using (IBM SPSS version 28). Normality was checked by using Shapiro Wilk test and Q-Q plots. Independent t-test was then used to analogize the groups. RESULTS: Mean ± standard deviation of retention force records ranged from 1731.57 (63.68) N (group STA) to 1032.29 (89.82) N (group ASC), and there was a statistically significant variation between the 2 groups (P < .05). Failure modes were Type 2 for group STA and Type 3 for group ASC. CONCLUSIONS: The retention of zirconia crowns to abutments with a straight screw access channel is significantly higher than abutments with angled screw access channel.