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Abstract Serious infection is common in patients with multiple myeloma due to immune deficiency from the underlying disease and/or its treatment. Immunoglobulin replacement is one approach to reduce infection risk in these patients. However, few real‐world data exist on its use in patients with myeloma. We investigated immunoglobulin use in Australia, New Zealand and Asia‐Pacific using registry data and explored its association with survival outcomes. A total of 2374 patients with a median follow‐up time of 29.5 months (interquartile range 13.3–54.3 months) were included in the analysis – 1673 from Australia, 313 Korea, 281 New Zealand and 107 Singapore. Overall, 7.1% of participants received immunoglobulin replacement within 24 months of diagnosis. Patients who received immunoglobulin replacement were likely to be younger, had lower baseline IgG levels (excluding paraprotein), were more likely to have baseline hypogammaglobulinaemia, baseline severe hypogammaglobulinaemia and abnormal baseline fluorescent in‐situ hybridisation status, receive first‐line myeloma treatment with immunomodulatory drugs or anti‐CD38 therapy and undergo upfront autologous stem cell transplant. In our patient cohort, the use of immunoglobulin was not associated with overall survival benefit at the time of last follow‐up (adjusted hazard ratio 0.72, 95% CI 0.46–1.14, p = 0.16). Understanding treatment approaches in clinical practice can help support future planning and provision of immunoglobulin resources.

Abstract Background Despite recent advances, optimal therapeutic approaches applicable to subpopulations with primary central nervous system (CNS) lymphoma outside of clinical trials remain to be determined. Methods We performed a retrospective study of immunocompetent, adult patients with histologically confirmed diffuse large B‐cell lymphoma of the CNS (PCNSL). 190/204 (93%) patients (median age: 65) received one of five high‐dose methotrexate (HD‐MTX) containing chemotherapy regimens: MPV/Ara‐C (HD‐MTX, procarbazine, and vincristine, followed by cytarabine [Ara‐C]) (n = 94, 50%), MATRix (HD‐MTX, Ara‐C, thiotepa, and rituximab) (n = 19, 10%), HD‐MTX/Ara‐C (n = 31, 16%), HD‐MTX monotherapy (n = 35, 18%) and MBVP (HD‐MTX, carmustine, teniposide, prednisolone) (n = 11, 6%). Results Cumulative median HD‐MTX and Ara‐C doses were 17 g/m2 (range: 1–64 g/m2) and 12 g/m2 (0–32 g/m2) respectively. Using 14 g/m2 as the reference dose, the median HD‐MTX relative dose intensity (HD‐MTX‐RDI) was 1.25 (0.27‐4.57) with 84% receiving > 0.75. The overall response rate (ORR) was 72% (complete response: 50%) after completing HD‐MTX. At a median follow‐up of 3.41 years (0.06–9.42), progression‐free survival (PFS) and overall survival (OS) were different between chemotherapy cohorts, with the best outcomes achieved in the MPV/Ara‐C cohort (2‐year PFS 74%, 2‐year OS 82%; p = 0.0001 and p = 0.0024 respectively). On multivariate analysis, MPV/Ara‐C administration and HD‐MTX‐RDI > 0.75 were associated with longer PFS and OS. Conclusion Sequential, response‐adapted approaches can improve outcomes, even in older patients who are ineligible for a high‐intensity concurrent chemotherapy approach and do not undergo traditional consolidative strategies.

Abstract Background Listening to patient voices is critical, in terms of how people experience their condition as well as their treatment preferences. This research explored the patient journey, therapy attributes and goals among treatment experienced adults with chronic lymphocytic leukemia (CLL). We sought to understand patient experiences, needs and expectations to identify areas for improvement of treatment and care delivery. Methods Two online surveys were developed for completion by CLL patients. In Stage 1, participants completed a best-worst scaling (BWS) task to evaluate eleven previously validated healthcare journey moments that matter (MTM). Responses were used to generate the patient experience index (PEI) score. In Stage 2, participants completed a survey that included both a discrete choice experiment (DCE) to assess drivers of treatment preferences by evaluating the relative attribute importance (RAI) of seven features and a BWS exercise which explored long-term treatment goals. Results Twenty-five patients completed Stage 1 and thirty patients Stage 2. Treatment experience was balanced between oral and intravenous medication. The most important/least satisfied MTM were treatment effectiveness, access to support and other treatments as well as monitoring progress. The median PEI score was 66.2 (out of 100). DCE results demonstrated that patients most value treatments for CLL that are associated with prolonged progression free survival (PFS; RAI: 24.6%), followed by treatments that have a lower risk of severe side effects and lower out-of-pocket costs (RAI: 19.5%, 17.4%, respectively). The remainder of the weight in decision making (38.5%) was split between the remaining attributes, namely ‘mild to moderate side effects’ (13.4%), ‘long-term risks’ (12.2%), type of treatment (i.e., oral, IV or a combination of oral and IV; 8.7%) and treatment duration (i.e., ongoing versus fixed; 4.2%). Patients preferred oral to intravenous therapy. The most valued long-term treatment goal was to be physically healthy, followed by living a long life, spending time with family/friends, and avoiding hospitalization. Conclusion Treatment experienced patients with CLL are focused on receiving effective, safe therapies and value long PFS. Consideration and discussion of other attributes, such as once daily dosing, oral only medication, out-of-pocket costs and access to support services may affect patient treatment choices and ultimately enhance their healthcare experience and outcomes.

Background: Melatonin is a peptide neurohormone naturally synthesized in the brain by the pineal gland. The basic function of melatonin is related to the causation and regulation of the sleep–wake cycle (circadian cycle). Cadmium (Cd) is a hazardous heavy metal and its toxic effects induce extensive tissue damage. The present study was undertaken to elucidate the efficiency of exogenous melatonin in attenuating Cd-induced oxidative stress. Methods: The experimental rats were allotted into four groups (n = 20), designated as untreated control, melatonin accessed, Cd exposed, and Cd exposed with access. Results: The hematological and biochemical parameters (serum and tissues) of Cd-exposed rats were significantly altered. Cd-exposed rats that received melatonin demonstrated increased erythrocytic indices; showed significantly increased levels of total proteins, catalase, total thiols, and glutathione; and exhibited decreased levels of blood Cd, urea, creatinine, bilirubin, malondialdehyde, and hydrogen peroxide. Conclusions: It was concluded that melatonin has an efficient antioxidant activity in attenuating oxidative stress induced by Cd.

Abstract Polatuzumab vedotin (Pola) is an approved therapy in combination with rituximab and bendamustine for relapsed or refractory diffuse large B‐cell lymphoma (RR‐DLBCL) based on positive results of the landmark phase II randomised G029365 trial. However, trial results for many approved novel therapies in RR‐DLBCL have not been replicated in routine care cohorts, as RR‐DLBCL patient populations are heterogeneous and trial eligibility is increasingly restrictive. We evaluated outcomes from pola ± bendamustine and rituximab in patients with RR‐DLBCL enrolled in a compassionate access program with no alternative treatment options identified via the Australasian Lymphoma and Related Diseases Registry according to their eligibility for the original phase II published study. Of 58 eligible patients, 74% met the criteria deeming them ineligible for the G029365 original study at the time of pola's commencement. Median progression‐free survival and overall survival in our cohort were 2.3 and 3.5 months, respectively. In contrast to the landmark trial cohort, more of our patients ceased therapy prior to completion, the majority due to progressive disease and only 8/58 received any subsequent treatment. Dismal outcomes in this Australian real‐world population demonstrate trial eligibility is challenging to meet, and newer treatments can be difficult to deliver in routine care. Clinically applicable results from therapeutic studies require trial cohorts to reflect representative clinical populations wherever possible, and more research is required to address the benefit of novel agents in the increasing majority who are ineligible for modern studies.

Background: The present study was carried out to test the antioxidant activity of lactoferrin as a dietary supplement to alleviate the effects of oxidative stress induced by mercury toxicity. Hematological and biochemical assays were employed to evaluate the ameliorating effects of lactoferrin. Methods: Sixty male Wistar rats were allotted randomly and equally into three groups; animals in Group 1 served as untreated control, animals in Group 2 were administered orally with mercuric chloride (HgCl2) at the dose of 6 mg/kg bw/day, and animals in Group 3 were administered with HgCl2 at the same dose and orally dosed with lactoferrin (400 mg/kg bw/day). Hematological indices (erythrocytic and total leukocytic counts, hemoglobin concentration%, and packed cell volume, (PCV%), and biochemical parameters (serum and homogenates of liver and kidney tissues) were assessed in all animals. Serum and tissue homogenate levels of total thiols, glutathione (GSH), catalase, and total antioxidant capacity (TAC) represented the antioxidant markers. The oxidation markers were represented by H2O2 and malondialdehyde (MDA). Results: Compared to the untreated control group, animals in Group 2 (administered with HgCl2) exhibited significantly increased levels of serum enzymes (alanine transferase (ALT), aspertate transferase (AST), and alkaline phosphatase), urea, blood urea nitrogen, creatinine, H2O2, and MDA. These animals showed significantly decreased levels of erythrocytic and total leukocytic counts, hemoglobin concentration, PCV%, total proteins, total thiols, GSH, catalase, and TAC. The hematological and biochemical changes were comparatively reversed toward the control levels in animals of Group 3 (administered with HgCl2 and orally dosed with lactoferrin). The reversed levels of hematological and biochemical parameters were significantly different compared to Group 2. Conclusions: Based on the encountered amelioration of the assayed hematological and biochemical parameters in animals treated with HgCl2 and given lactoferrin, it could be concluded that lactoferrin as a dietary supplement might function as an efficient antioxidant to alleviate the oxidative stress induced by mercury toxicity.

Promoting access to and excellence in hematopoietic cell transplantation (HCT) by collecting and disseminating data on global HCT activities is one of the principal activities of the Worldwide Network for Blood and Marrow Transplantation, a non-Governmental organization in working relations with the World Health Organization. HCT activities are recorded annually by member societies, national registries and individual centers including indication, donor type (allogeneic/autologous), donor match and stem cell source (bone marrow/peripheral blood stem cells/cord blood). In 2018, 1,768 HCT teams in 89 countries (six WHO regions) reported 93,105 (48,680 autologous and 44,425 allogeneic) HCT. Major indications were plasma cell disorders and lymphoma for autologous, and acute leukemias and MDS/MPN for allogeneic HCT. HCT number increased from 48,709 in 2007. Notable increases were seen for autoimmune diseases in autologous and hemoglobinopathies in allogeneic HCT. The number of allogeneic HCT more than doubled with significant changes in donor match. While HCT from HLA identical siblings has seen only limited growth, HCT from non-identical related donors showed significant increase worldwide. Strongest correlation between economic growth indicator of gross national income/capita and HCT activity/ten million population was observed for autologous HCT (r=0.79). HCT from unrelated donors showed strong correlation (r=0.68), but only moderate correlation (r=0.51) was detected from related donors. The use of HCT doubled in about a decade worldwide at different speed and with significant changes regarding donor match as a sign of improved access to HCT worldwide. Although narrowing, significant gaps remain between developing and non-developing countries.

Cement mortar without fibers might crack due to shrinkage or volume changes. Cracking in cement mortar leads to elastic deformation. The development of these cracks causes elastic deformation of cement mortar. This study examined the influence of two steel fibers' geometrical forms (crimped and hooked with just one end) in different amounts by volume (Volume fraction = 0.25%, 0.5%, and 0.75%) on the cement mortar's mechanical features. Among the characteristics were splitting, compressive as well as flexural strength. The samples were prepared, poured into cubic molds for compressive strength testing cylindrical molds used for splitting strength testing, and prismatic molds for flexural strength testing, and processed at various times 3, 14, and 28 days before the tests. According to the findings, the highest increase was obtained after adding 0.75% of crimped fibers, the compressive strength increased by 13.3 %21.29%, and 44.8%, for 3,14.28 days respectively, and split tensile strength increased by 66.17%,68.9%, and 79.48% for 3.14 and 28 days respectively and flexural strength increased by 72 %,91% and 92% for 3.14 and 28 days, respectively.

**Background:** The mainstay first-line therapy for chronic graft-vs-host disease (cGVHD) is corticosteroids; however, for steroid-refractory patients, there is a distinct lack of cost-effective or efficacious treatment. The aim of this study was to assess the cost-effectiveness of extracorporeal photopheresis (ECP) compared with standard-of-care therapies for the treatment of cGVHD in Australia. The study formed part of an application to the Australian Government to reimburse ECP for these patients. **Methods:** A cost-utility analysis was conducted comparing ECP to standard of care, which modeled the response to treatment and disease progression of cGVHD patients in Australia. Mycophenolate, tacrolimus, and cyclosporin comprised second-line standard of care based on a survey of Australian clinicians. Health states in the model included treatment response, disease progression, and death. Transition probabilities were obtained from Australian-specific registry data and randomized controlled evidence. Quality-of-life values were applied based on treatment response. The analysis considered costs of second-line treatment and disease management including immunosuppressants, hospitalizations and subsequent therapy. Disease-specific mortality was calculated for treatment response and progression. **Results:** Over a 10-year time horizon, ECP resulted in an average cost reduction of $23 999 and an incremental improvement of 1.10 quality-adjusted life-years per patient compared with standard of care. The sensitivity analysis demonstrated robustness over a range of plausible scenarios. **Conclusion:** This analysis demonstrates that ECP improves quality of life, minimizes the harms associated with immunosuppressant therapy, and is a highly cost-effective option for steroid-refractory cGVHD patients in Australia. Based in part on this analysis, ECP was listed on the Medicare Benefits Schedule for public reimbursement.

Abstract Background The incidence of pregnancy-associated cancer (PAC), comprising cancer diagnosed during pregnancy or within one year postpartum, is increasing. We investigated the obstetric management and outcomes of women with PAC and their babies. Methods A population-based observational study of all women who gave birth between 1994 and 2013 in New South Wales, Australia. Women were stratified into three groups: those diagnosed during pregnancy (gestational cancer group), those diagnosed within one year of giving birth (postpartum cancer group), and a no-PAC group. Generalized estimating equations were used to examine the association between PAC and adverse maternal and neonatal outcomes. Results One million seven hundred eighty-eight thousand four hundred fifty-onepregnancies were included—601 women (614 babies) were in the gestational cancer group, 1772 women (1816 babies) in the postpartum cancer group, and 1,786,078 women (1,813,292 babies) in the no-PAC group. The overall crude incidence of PAC was 132.7/100,000 women giving birth. The incidence of PAC increased significantly over the twenty-year study period from 93.5/100,000 in 1994 to 162.5/100,000 in 2013 (2.7% increase per year, 95% CI 1.9 – 3.4%, p-value

Grade (G) 3B follicular lymphoma (FL) is a rare FL subtype which exists on a histological continuum between ‘lowgrade’ (Grade 1, 2 and 3A FL) and diffuse large B-cell lymphoma (DLBCL) appearing to share features with each. Clinical characteristics and outcomes are poorly understood due to lack of adequate representation in prospective trials and large-scale analyses. We analyzed 157 G3BFL cases from 18 international centers, and two comparator groups; G3AFL (n=302) and DLBCL (n=548). Composite histology with DLBCL or low-grade FL occurred in approximately half of the G3BFL cases. With a median of 5 years follow-up, the overall survival and progression-free survival of G3BFL patients was better than that of DLBCL patients (P

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment for myelofibrosis. However, the optimal conditioning regimen either with reduced-intensity conditioning (RIC) or myeloablative conditioning (MAC) is not well known. Using the Center for International Blood and Marrow Transplant Research database, we identified adults aged ≥18 years with myelofibrosis undergoing allo-HCT between 2008-2019 and analyzed the outcomes separately in the RIC and MAC cohorts based on the conditioning regimens used. Among 872 eligible patients, 493 underwent allo-HCT using RIC (fludarabine/ busulfan n=166, fludarabine/melphalan n=327) and 379 using MAC (fludarabine/busulfan n=247, busulfan/cyclophosphamide n=132). In multivariable analysis with RIC, fludarabine/melphalan was associated with inferior overall survival (hazard ratio [HR]=1.80; 95% confidenec interval [CI]: 1.15-2.81; P=0.009), higher early non-relapse mortality (HR=1.81; 95% CI: 1.12-2.91; P=0.01) and higher acute graft-versus-host disease (GvHD) (grade 2-4 HR=1.45; 95% CI: 1.03-2.03; P=0.03; grade 3-4 HR=2.21; 95%CI: 1.28-3.83; P=0.004) compared to fludarabine/busulfan. In the MAC setting, busulfan/cyclophosphamide was associated with a higher acute GvHD (grade 2-4 HR=2.33; 95% CI: 1.67-3.25; P

Abstract Patients with RR DLBCL who have received ≥ 2 lines of therapy have limited treatment options and an expected overall survival (OS) of

Background Cancer and diabetes have a tremendous impact on health globally. This study aimed to evaluate the KRAS gene in colon cancer tissues obtained from patients with type 2 diabetes mellitus (T2DM). Materials and Methods Data from 315 cases (156 colon diabetics and 159 patients were nondiabetics) were retrospectively retrieved. mRNA from surgically resected colon cancer tumors were also retrieved. Results The expression of KRAS mRNA was significantly higher in patients afflicted with T2DM than nondiabetic patients. The KRAS mRNA levels were significantly amplified from primary to metastatic lesions (p

There are limited data on post-transplant lymphoproliferative disorder (PTLD) in the era of positron emission tomography (PET) and rituximab (R). Furthermore, there is limited data on the risk of graft rejection with modern practices in reduction in immunosuppression (RIS). We studied 91 patients with monomorphic diffuse large B-cell lymphoma PTLD at 11 Australian centers: median age 52 years, diagnosed between 2004 and 2017, median follow-up 4.7 years (range, 0.5–14.5 y). RIS occurred in 88% of patients. For patients initially treated with R-monotherapy, 45% achieved complete remission, rising to 71% with the addition of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP) for those not in complete remission. For patients initially treated with R-CHOP, the complete remission rate was 76%. There was no difference in overall survival (OS) between R-monotherapy and R-chemotherapy patients. There was no difference in OS for patients with systemic lymphoma (n = 68) versus central nervous system (CNS) involvement (n = 23) (3-y OS 72% versus 73%; P = 0.78). Treatment-related mortality was 7%. End of treatment PET was prognostic for patients with systemic lymphoma with longer OS in the PET negative group (3-y OS 91% versus 57%; P = 0.01). Graft rejection occurred in 9% (n = 4 biopsy-proven; n = 4 suspected) during the entire follow-up period with no cases of graft loss. RIS and R-based treatments are safe and effective with a low likelihood of graft rejection and high cure rate for patients achieving complete remission with CNS or systemic PTLD.

The Worldwide Network of Blood and Marrow Transplantation (WBMT) pursues the mission of promoting hematopoietic cell transplantation (HCT) for instance by evaluating activities through member societies, national registries and individual centers. In 2016, 82,718 first HCT were reported by 1,662 HCT teams in 86 of the 195 World Health Organization member states representing a global increase of 6.2% in autologous HCT and 7.0% in allogeneic HCT and bringing the total to 1,298,897 procedures. Assuming a frequency of 84,000/year, 1.5 million HCT were performed by 2019 since 1957. Slightly more autologous (53.5%) than allogeneic and more related (53.6%) than unrelated HCT were reported. A remarkable increase was noted in haploidentical related HCT for leukemias and lymphoproliferative diseases, but even more in non-malignant diseases. Transplant rates (TR; HCT/10 million population) varied according to region reaching 560.8 in North America, 438.5 in Europe, 76.7 in Latin America, 53.6 in South East Asia/Western Pacific (SEA/WPR) and 27.8 in African/East Mediterranean (AFR/EMR). Interestingly, haploidentical TR amounted to 32% in SEA/WPR and 26% in Latin America, but only 14% in Europe and EMR and 4.9% in North America of all allogeneic HCT. HCT team density (teams/10 million population) was highest in Europe (7.7) followed by North America (6.0), SEA/WPR (1.9), Latin America (1.6) and AFR/EMR (0.4). HCT are increasing steadily worldwide with narrowing gaps between regions and greater increase in allogeneic compared to autologous activity. While related HCT is rising, largely due to increase in haploidentical HCT, unrelated HCT is plateauing and cord blood HCT is in decline.

Background: Vaccination is the cornerstone of the global public health response to the COVID-19 pandemic. Excess morbidity and mortality of COVID-19 infection is seen in people with cancer. COVID-19 vaccine hesitancy has been observed in this medically vulnerable population, although associated attitudes and beliefs remain poorly understood. Methods: An online cross-sectional survey of people with solid organ cancers was conducted through nine health services across Australia. Demographics, cancer-related characteristics and vaccine uptake were collected. Perceptions and beliefs regarding COVID-19 vaccination were assessed using the Oxford COVID-19 Vaccine Hesitancy Scale, the Oxford COVID-19 Vaccine Confidence and Complacency Scale and the Disease Influenced Vaccine Acceptance Scale-6. Results: Between June and October 2021, 2691 people with solid organ cancers completed the survey. The median age was 62.5 years (SD = 11.8; range 19–95), 40.9% were male, 71.3% lived in metropolitan areas and 90.3% spoke English as their first language. The commonest cancer diagnoses were breast (36.6%), genitourinary (18.6%) and gastrointestinal (18.3%); 59.2% had localized disease and 56.0% were receiving anti-cancer therapy. Most participants (79.7%) had at least one COVID-19 vaccine dose. Vaccine uptake was higher in people who were older, male, metropolitan, spoke English as a first language and had a cancer diagnosis for more than six months. Vaccine hesitancy was higher in people who were younger, female, spoke English as a non-dominant language and lived in a regional location, and lower in people with genitourinary cancer. Vaccinated respondents were more concerned about being infected with COVID-19 and less concerned about vaccine safety and efficacy. Conclusions: People with cancer have concerns about acquiring COVID-19, which they balance against vaccine-related concerns about the potential impact on their disease progress and/or treatment. Detailed exploration of concerns in cancer patients provides valuable insights, both for discussions with individual patients and public health messaging for this vulnerable population.

As COVID-19 vaccinations became available and were proven effective in preventing serious infection, uptake amongst individuals varied, including in medically vulnerable populations. This cross-sectional multi-site study examined vaccine uptake, hesitancy, and explanatory factors amongst people with serious and/or chronic health conditions, including the impact of underlying disease on attitudes to vaccination. A 42-item survey was distributed to people with cancer, diabetes, or multiple sclerosis across ten Australian health services from 30 June to 5 October 2021. The survey evaluated sociodemographic and disease-related characteristics and incorporated three validated scales measuring vaccine hesitancy and vaccine-related beliefs generally and specific to their disease: the Oxford COVID-19 Vaccine Hesitancy Scale, the Oxford COVID-19 Vaccine Confidence and Complacency Scale and the Disease Influenced Vaccine Acceptance Scale-Six. Among 4683 participants (2548 [54.4%] female, 2108 [45.0%] male, 27 [0.6%] other; mean [SD] age, 60.6 [13.3] years; 3560 [76.0%] cancer, 842 [18.0%] diabetes, and 281 [6.0%] multiple sclerosis), 3813 (81.5%) self-reported having at least one COVID-19 vaccine. Unvaccinated status was associated with younger age, female sex, lower education and income, English as a second language, and residence in regional areas. Unvaccinated participants were more likely to report greater vaccine hesitancy and more negative perceptions toward vaccines. Disease-related vaccine concerns were associated with unvaccinated status and hesitancy, including greater complacency about COVID-19 infection, and concerns relating to vaccine efficacy and impact on their disease and/or treatment. This highlights the need to develop targeted strategies and education about COVID-19 vaccination to support medically vulnerable populations and health professionals.

We introduce two powerful methods to solve the Davey-Stewartson equations: one is the homotopy perturbation method (HPM) and the other is the homotopy analysis method (HAM). HAM is a strong and easy to use analytic tool for nonlinear problems. Comparison of the HPM results with the HAM results, and compute the absolute errors between the exact solutions of the DS equations with the HPM solutions and HAM solutions are obtained.

Cement mortar without fibers might crack due to shrinkage or volume changes. Cracking in cement mortar leads to elastic deformation. The development of these cracks causes elastic deformation of cement mortar. This study examined the influence of two steel fibers' geometrical forms (crimped and hooked with just one end) in different amounts by volume (Volume fraction = 0.25%, 0.5%, and 0.75%) on the cement mortar's mechanical features. Among the characteristics were splitting, compressive as well as flexural strength. The samples were prepared, poured into cubic molds for compressive strength testing cylindrical molds used for splitting strength testing, and prismatic molds for flexural strength testing, and processed at various times 3, 14, and 28 days before the tests. According to the findings, the highest increase was obtained after adding 0.75% of crimped fibers, the compressive strength increased by 13.3 %21.29%, and 44.8%, for 3,14.28 days respectively, and split tensile strength increased by 66.17%,68.9%, and 79.48% for 3.14 and 28 days respectively and flexural strength increased by 72 %,91% and 92% for 3.14 and 28 days, respectively. [ABSTRACT FROM AUTHOR]

Background: Melatonin is a peptide neurohormone naturally synthesized in the brain by the pineal gland. The basic function of melatonin is related to the causation and regulation of the sleep–wake cycle (circadian cycle). Cadmium (Cd) is a hazardous heavy metal and its toxic effects induce extensive tissue damage. The present study was undertaken to elucidate the efficiency of exogenous melatonin in attenuating Cd-induced oxidative stress. Methods: The experimental rats were allotted into four groups(n = 20), designated as untreated control, melatonin accessed, Cd exposed, and Cd exposed with access. Results: The hematological and biochemical parameters(serum and tissues) of Cd-exposed rats were significantly altered. Cd‑exposed rats that received melatonin demonstrated increased erythrocytic indices; showed significantly increased levels of total proteins, catalase, total thiols, and glutathione; and exhibited decreased levels of blood Cd, urea, creatinine, bilirubin, malondialdehyde, and hydrogen peroxide. Conclusions: It was concluded that melatonin has an efficient antioxidant activity in attenuating oxidative stress induced by Cd. [ABSTRACT FROM AUTHOR]

Background: The present study was carried out to test the antioxidant activity of lactoferrin as a dietary supplement to alleviate the effects of oxidative stress induced by mercury toxicity. Hematological and biochemical assays were employed to evaluate the ameliorating effects of lactoferrin. Methods: Sixty male Wistar rats were allotted randomly and equally into three groups; animals in Group 1 served as untreated control, animals in Group 2 were administered orally with mercuric chloride (HgCl2) at the dose of 6 mg/kg bw/day, and animals in Group 3 were administered with HgCl2 at the same dose and orally dosed with lactoferrin (400 mg/kg bw/day). Hematological indices (erythrocytic and total leukocytic counts, hemoglobin concentration%, and packed cell volume, (PCV%), and biochemical parameters (serum and homogenates of liver and kidney tissues) were assessed in all animals. Serum and tissue homogenate levels of total thiols, glutathione (GSH), catalase, and total antioxidant capacity (TAC) represented the antioxidant markers. The oxidation markers were represented by H2O2 and malondialdehyde (MDA). Results: Compared to the untreated control group, animals in Group 2 (administered with HgCl2) exhibited significantly increased levels of serum enzymes (alanine transferase (ALT), aspertate transferase (AST), and alkaline phosphatase), urea, blood urea nitrogen, creatinine, H2O2, and MDA. These animals showed significantly decreased levels of erythrocytic and total leukocytic counts, hemoglobin concentration, PCV%, total proteins, total thiols, GSH, catalase, and TAC. The hematological and biochemical changes were comparatively reversed toward the control levels in animals of Group 3 (administered with HgCl2 and orally dosed with lactoferrin). The reversed levels of hematological and biochemical parameters were significantly different compared to Group 2. Conclusions: Based on the encountered amelioration of the assayed hematological and biochemical parameters in animals treated with HgCl2 and given lactoferrin, it could be concluded that lactoferrin as a dietary supplement might function as an efficient antioxidant to alleviate the oxidative stress induced by mercury toxicity. [ABSTRACT FROM AUTHOR]

The study aimed to screen for PIK3CA gene mutations among Saudi women with Ovarian Cancer. The study included 298 Saudi women with epithelial ovarian cancers (EOC). DNA sequence analysis was employed to screen for the mutations. DNA sequence analysis of a coding region of exon 9 and 20 of PIK3CA gene revealed mutations in 37/298 (12.4%) EOC patients. About 21/37(56.8%) somatic mutations were identified in exons 9, and 16/37(43.2%) in exon 20. All analysed mutations were missense mutations, the frequencies of which varied from 2.7% to 43.2%. PIK3CA mutation was found to be significantly associated with age (p =.023), grade (p =.001) and histological types (p =.032). Only 6.6% of serous carcinomas and 3.8% of endometrioid had PIK3CA mutation. The Mutated PIK3CA gene was significantly involved in the pathogenesis of EOC among Saudi women. PIK3CA gene mutation and overexpression represent important clinical implications for diagnosis, and prognosis, which can be utilised for better EOC management. What is already known on this subject? The detailed molecular and genetic phenomenon underlying the progression of these tumours is still unclear. Recently, the pathogenesis of ovarian cancer has been attributed to mutations of PIK3CA. What do the results of this study add? Mutation in the PIK3CA gene leads to altered PI3K/AKT signalling pathways responsible for the progression of the epithelial ovarian cancer. What are the implications of these findings for clinical practice and/or further research? The Mutated PIK3CA gene was significantly involved in the pathogenesis of EOC among Saudi women. PIK3CA gene mutation and overexpression represent important clinical implications for diagnosis, and prognosis, which can be utilised for better EOC management. [ABSTRACT FROM AUTHOR]

Background: In recent years, there is an emerging increase in the prevalence of oral and oropharyngeal cancers (O-OPCs) across the Arabian Gulf Cooperation Council (GCC) countries. Consequently, this review aimed to explore the epidemiology and possible risk factors of O-OPCs in GCC countries., Methods: Data published after 2008 related to O-OPCs in GCC countries were obtained through electronic searches in Medline/PubMed, Scopus, Web of Science, EMBASE and Google Scholar. Keywords related to the association between O-OPCs metrics (epidemiology and risk factors) and GCC countries were used for electronic searches., Results: The overall prevalence of OPCs increased significantly over time (40-51%) in some countries (Saudi Arabia and Arab Emigrated) of the Gulf regions. The pooled risk factor was 3.4 (2.5 - 4.7). Among the risk factors, human papillomavirus and the use of smoke and smokeless tobacco revealed odds ratio (OR) 3.31 (3.13 - 4.5) and 0.60 (0.45 - 0.80) at 95% confidence interval (CI)., Conclusion: A positive correlation between factors like age, diet, hygiene, genetics, viral and bacterial infection, consumption of alcohol and tobacco products with OPC-MFC is suggested., Competing Interests: The authors declare that there is no conflict of interest., (Copyright 2020, Alqahtani et al.)

Background  Cancer and diabetes have a tremendous impact on health globally. This study aimed to evaluate the KRAS gene in colon cancer tissues obtained from patients with type 2 diabetes mellitus (T2DM). Materials and Methods  Data from 315 cases (156 colon diabetics and 159 patients were nondiabetics) were retrospectively retrieved. mRNA from surgically resected colon cancer tumors were also retrieved. Results  The expression of KRAS mRNA was significantly higher in patients afflicted with T2DM than nondiabetic patients. The KRAS mRNA levels were significantly amplified from primary to metastatic lesions ( p  < 0.001). Conclusion  The association between T2DM and colon cancer was well-established in the present study., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)