Engineered peptides for the development of actively tumor targeted liposomal carriers of doxorubicin

Chemotherapy is still the treatment of choice for many types of cancer; but its effectiveness is hampered by dose limiting toxicity. Properly designed delivery systems can overcome this shortcoming by reducing the non-specific distribution and toxicity of chemotherapeutics in healthy organs and at the same time increasing drug concentrations at tumor tissue. In this study, we developed stealth liposomal formulations of doxorubicin (DOX) having a novel stable engineered peptide ligand, namely p18-4, that binds specifically to breast cancer cell line MDA-MB-435 on its surface. The coupling of p18-4 to liposomes was carried out through conventional, post insertion and post conjugation techniques and prepared liposomes were characterized for their size and level of peptide modification. The p18-4 decorated liposomal DOX formulations were then evaluated for their cellular uptake as well as cytotoxicity against the human breast cancer MDA-MB-435 cells. In this context, the effect of coupling technique on the uptake and cytotoxicity of p18-4 liposomal DOX in MDA-MB-435 cells was evaluated. The conventional and post conjugation methods of peptide incorporation were found to be more reliable for the preparation of p18-4 decorated liposomes for active DOX targeting to MDA-MB-435 cells. p18-4 decoration of liposomes by these methods did not have a notable effect on the size of prepared liposomes and DOX release, but increased the uptake and cytotoxicity of encapsulated DOX in MDA-MB-435 cells. The results show a potential for p18-4 decorated liposomes prepared by conventional and post conjugation method for tumor targeted delivery of DOX in breast tumor models.     

Gender difference in albuminuria and ischemic heart disease in type 2 diabetes

Objective

The value of urinary albumin excretion in the prediction of myocardial ischemia in men and women with type 2 diabetes is not well understood. We questioned whether gender influences the albuminuria-ischemic heart disease relationship in patients with type 2 diabetes.

Methods

We designed a matched case-control study of 926 patients with albuminuria (cases) and 926 age and body mass index matched patients without albuminuria (controls). Ischemic heart disease was defined as the presence of (1) history of angina pectoris or angina equivalent symptoms and critical care unit admission, (2) myocardial infarction and/or electrocardiographic evidence of Q-wave myocardial infarction, (3) coronary revascularization and/or stenting, (4) positive myocardial single-photon emission computed tomography scan, (5) ischemic ST-segment or T-wave changes, and (6) positive stress testing.

Results

Patients with albuminuria had a lower glomerular filtration rate and a longer diabetes duration than patients without albuminuria. In the group of cases, there were a greater number of men with ischemic heart disease (120 of 370; 32.4%) compared to women (97 of 559; 17.4%) (P<0.001). The odds ratio of having ischemic heart disease according to the presence or absence of albuminuria was 1.25 [95% CI: 1.01–1.56] (P<0.05) in all studied populations, 0.79 [95% CI: 0.51–1.21] (P=0.14) in women, and 2.84 [95% CI: 1.68–4.79] (P<0.001) in men. We showed that diabetes duration, high-density lipoprotein, low-density lipoprotein, and hemoglobin A_1c influence albuminuria in women, while diabetes duration, fasting blood sugar, and diastolic blood pressure influence albuminuria in men.

Conclusions

Men with albuminuria are at increased risk of ischemic heart disease compared to women. This may be related to the role of high-density lipoprotein on the albuminuria-gender relationship.     

Salvadora Persica extract chewing gum and gingival health: Improvement of gingival and probe-bleeding index

Previous studies showed that Persica extracts have antibacterial activity against cariogenic and periodontopathic bacteria and can develop periodontal health; however, the clinical effects of gum as a delivery device for Persica to periodontal health in human, have not yet been investigated. The objective of this study was to evaluate the effect of chewing gum containing Persica extract on periodontal health in a double-masked, randomized trial. From a high school in Babol, 72 cases with plaque induced moderate gingivitis were randomly assigned to the 2 weeks trial in the following groups: S+/P+ (n = 18): use of Persica extract chewing gum for 2 weeks and two sessions of scaling; S+/P? (n = 18): use of placebo chewing gum two sessions of scaling; S?/P+ (n = 18): use of Persica extract chewing gum; and S?/P? (n = 18): use of placebo chewing gum. Plaque index (PI), gingival index (GI), and bleeding index (BI), were measured at days 0, 7, and 14. Data was analyzed with t test or Mann–Whitney U test. Seven patients from Persica scaling group and five patients from Persica no scaling (S?/P+) group were excluded for complaining about the taste and irritation. The effects of extract chewing gum was statistically significant in reduction of GI, and BI but not for PI in Persica groups compared with the placebo groups in the days of 7 and 14 after the beginning of trial. Persica extract chewing gum had a considerable effect on GI, and BI. The use of Salvadora persica extract chewing gum may promote periodontal health.     

Colorectal cancer statistics, 2017

Colorectal cancer (CRC) is one of the most common malignancies in the United States. Every 3 years, the American Cancer Society provides an update of CRC incidence, survival, and mortality rates and trends. Incidence data through 2013 were provided by the Surveillance, Epidemiology, and End Results program, the National Program of Cancer Registries, and the North American Association of Central Cancer Registries. Mortality data through 2014 were provided by the National Center for Health Statistics. CRC incidence rates are highest in Alaska Natives and blacks and lowest in Asian/Pacific Islanders, and they are 30% to 40% higher in men than in women. Recent temporal patterns are generally similar by race and sex, but differ by age. Between 2000 and 2013, incidence rates in adults aged ≥50 years declined by 32%, with the drop largest for distal tumors in people aged ≥65 years (incidence rate ratio [IRR], 0.50; 95% confidence interval [95% CI], 0.48‐0.52) and smallest for rectal tumors in ages 50 to 64 years (male IRR, 0.91; 95% CI, 0.85‐0.96; female IRR, 1.00; 95% CI, 0.93‐1.08). Overall CRC incidence in individuals ages ≥50 years declined from 2009 to 2013 in every state except Arkansas, with the decrease exceeding 5% annually in 7 states; however, rectal tumor incidence in those ages 50 to 64 years was stable in most states. Among adults aged <50 years, CRC incidence rates increased by 22% from 2000 to 2013, driven solely by tumors in the distal colon (IRR, 1.24; 95% CI, 1.13‐1.35) and rectum (IRR, 1.22; 95% CI, 1.13‐1.31). Similar to incidence patterns, CRC death rates decreased by 34% among individuals aged ≥50 years during 2000 through 2014, but increased by 13% in those aged <50 years. Progress against CRC can be accelerated by increasing initiation of screening at age 50 years (average risk) or earlier (eg, family history of CRC/advanced adenomas) and eliminating disparities in high‐quality treatment. In addition, research is needed to elucidate causes for increasing CRC in young adults. CA Cancer J Clin 2017. © 2017 American Cancer Society. CA Cancer J Clin 2017;67:177–193 . © 2017 American Cancer Society .     

Proceeding report of the third symposium on Hidradenitis Suppurativa advances (SHSA) 2018

The 3rd Annual Symposium on Hidradenitis Suppurativa Advances (SHSA) took place on 12‐14 October 2018 at the Women's College Hospital in Toronto, Ontario, Canada. This symposium was a joint meeting of the Hidradenitis Suppurativa Foundation (HSF) founded in the USA and the Canadian Hidradenitis Suppurativa Foundation (CHSF). This cross‐disciplinary meeting with experts from around the world was an opportunity to discuss the most recent advances in the study of hidradenitis suppurativa pathogenesis, epidemiology, classification, scoring systems, radiologic diagnosis, treatment approaches and psychologic assessment. Two special sessions this year were HS as a systemic disease and HS management guidelines. There were focused workshops on wound healing and ultrasound. There were two sessions primarily for patients and their families in the HS School programme: One workshop focused on mindfulness, and the second involved discussion among clinicians and patients about various disease aspects and the latest management. To facilitate networking between clinical and research experts and those early in their career, a mentoring breakfast was held.     

Infidelity and Its Associated Factors: A Systematic Review

BackgroundInfidelity can be facilitated and/or inhibited as a result of interrelations among multilevel contexts. Despite the existence of numerous studies about infidelity, there is no developmental model that considers multilevel contexts of factors associated with infidelity.AimTo review published articles addressing factors associated with infidelity and to apply the ecological model to these factors.MethodsA systematic review of the literature was conducted using the PubMed, Scopus, Web of Science, and PsychoInfo. Literature search was restricted to articles published in English up to June 2018. All quantitative and full-text studies that addressed associated factors with infidelity were included. This study was conducted following PRISMA guidelines.Main Outcome MeasuresThis article reports a review of the literature on the factors associated with infidelity based on the ecological model.ResultsWe retrieved 5,159 titles, of which 82 were qualified after the qualitative synthesis. The Ecological Couples Systems Diagram (ECSD) is proposed as a developmental model similar to Bronfenbrenner’s Bioecological Systems Model. There was an inconsistency between variables of microsystem and infidelity engagement. However, the results of some studies indicated the impact of demographic factors, personality traits, and sexual information on infidelity, considering partner characteristics. Variables belonging to a mesosystem had a more stable association with infidelity than those from other systems. In addition, the review reveals the complexity of infidelity, associated with following factors: 68.3% (n = 56) of the studies were based on microsystem variables, 48.8% (n = 40) used mesosystem variables, 19.5% (n = 16) used exosystem variables, 26.8% (n = 22) used macrosystem variables, 6.1% (n = 5) used chronosystem variables, and 50% (n = 41) included variables from 2 or more levels.Clinical ImplicationsThe ECSD can be used not only for assessing couple compatibility in premarital counseling, but also for consulting couples who want to have a long-term romantic relationship. As a potential clinical application, therapists can use the ECSD to assess unfaithful clients and their partners, improving the quality of counseling.Strengths & LimitationsThis study reveals different environmental layers of various variables related to infidelity. Determining the effect size of variables associated with infidelity was not possible due to the heterogeneity of infidelity assessment tools and test analysis.ConclusionApparently, incompatibility of interpersonal characteristics is more likely associated with infidelity than incompatibility of intrapersonal characteristics. It is important to consider couple compatibility before starting an exclusive relationship, such as marriage, for individuals who intend to maintain a long-term exclusive romantic relationship.Haseli A, Shariati M, Nazari AM, et al. Infidelity and Its Associated Factors: A Systematic Review. J Sex Med 2019;16:1155–1169.     

Prevalence and risk factors for developing traumatic childbirth in Iran

Aim

Traumatic childbirth is among the important factors that make childbirth an unpleasant experience and has psychological negative effects on women. This study aimed to determine the prevalence and risk factors associated with traumatic childbirth.

Subject and methods

In this cross-sectional study, 400 women were interviewed in the first 48 h after childbirth in Torbate-heydariyeh (eastern Iran) in 2015. Traumatic childbirth was determined based on DSM-V-A criteria. Statistical analysis of the data was done through chi-square and logistic regression.

Results

The prevalence of traumatic childbirth was 48.3% (N?=?193). Logistic regression showed variables such as place of residence, type of delivery, pregnancy complications, bleeding during pregnancy, rupture of grade 3 or 4 during delivery, and emergency cesarean section were significantly correlated with traumatic childbirth (p <0.001).

Conclusion

Considering the high prevalence of traumatic childbirth, it is recommended that its associated risk factors be identified so that negative psychological consequences for the mother can be prevented.