Chemokine receptor CXCR4 expression in breast cancer as a potential predictive marker of isolated tumor cells in bone marrow

Interactions between the CXCR4 chemokine receptor in breast cancer cells and the ligand CXCL12/SDF-1α are thought to play an important role in breast cancer metastases. In this pilot study, CXCR4 expression along with other biomarkers including HER2-neu and EGFR, were measured in primary tumor samples of patients with operable breast cancer to test whether any of these biomarkers alone and in combination could indicate breast cancer with high likelihood of metastasizing to bone marrow. Cytokeratin (CK) positive cells in bone marrow were identified by flow-cytometry following enrichment with CK 7/8 antibody-coupled magnetic beads. Primary tumors (n = 18) were stained with specific antibodies for CXCR4, HER2-neu, EGFR, and PCNA using an indirect avidin–biotin horseradish peroxidase method. The majority of the patients had T2/T3 tumors (72%), or lymph node involvement (67%) as pathologic characteristics that were more indicative of high-risk breast cancer. High CXCR4 cytoplasmic expression was found in 7 of 18 patients (39%), whereas 6 of 18 patients (33%) were found to have CK positivity in bone marrow. The median number of CK⁺ cells was 236 (range, 20–847) per 5 × 10⁴ enriched BM cells. The presence of CK⁺ cells in bone marrow was found to be associated with increased expression of CXCR4 alone or in addition to EGFR and/or HER2-neu expression (P = 0.013, P = 0.005, and P = 0.025, respectively) in primary tumors. Furthermore, three patients with high CK positivity (>236 CK⁺ per 5 × 10⁴ enriched bone marrow cells) in bone marrow exclusively expressed high levels of CXCR4 with EGFR/HER2-neu (P = 0.001). Our data suggest that high CXCR4 expression in breast cancer may be a potential marker in predicting isolated tumor cells in bone marrow. CXCR4 coexpression with EGFR/HER2-neu might further predict a particular subset of patients with high CK positivity in bone marrow.     

Antigenic determinants of the OmpC porin from Salmonella typhimurium.

The antigenic determinants of Salmonella typhimurium OmpC were investigated by the analysis of cyanogen bromide (CNBr)-generated porin peptides with antiporin monoclonal antibodies (MAbs). We identified six bands (f1 to f6) with estimated molecular masses of 35.5, 31.0, 25.0, 22.5, 13.8, and 10.0 kDa, respectively. In addition, two small fragments (f7 and f8; 3.0 to 6.0 kDa) were detected only infrequently. The OmpC monomer or its CNBr-generated peptides were electrophoretically transferred to a polyvinylidene difluoride membrane and then subjected to amino acid composition analysis and N-terminal sequencing. A comparison of the amino acid composition data with known compositions of Escherichia coli and Salmonella typhi OmpC showed some differences; however, the amino acid sequences of 71 residues identified in S. typhimurium showed 88 and 98% identity with OmpC from E. coli and S. typhi, respectively. The screening of CNBr peptides with the 12 anti-(S. typhimurium) OmpC MAbs by Western blot (immunoblot), in conjunction with the prediction of the OmpC folding pattern based on the known three-dimensional structure of E. coli OmpF, showed that four MAbs reacted with surface-exposed epitopes on loops L2, L8, and L4 to L7, four MAbs reacted with a region in the eyelet structure on loop L3, and four MAbs reacted with the buried epitopes on transmembrane beta strands. The MAbs reacting with surface-exposed loops showed no cross-reaction with E. coli OmpC, whose sequence has diverged extensively from that of S. typhi and (probably) S. typhimurium OmpC only in regions of the externally exposed loops. In contrast, MAbs reacting with transmembrane beta strands, whose sequence is strongly conserved, showed strong cross-reaction with E. coli OmpC. These results show that comparison with the E. coli OmpF structure predicts the folding pattern of S. typhimurium OmpC rather accurately and that evolutionary divergence in sequences is confined to the external loops. The possible roles of these surface-exposed and buried epitopes as potentially useful antigenic regions for diagnostic assays and vaccine development are discussed.     

Problematic Smartphone Use: Prevalence and Associated Factors Among Health Sciences Students in Saudi Arabia

Journal of Prevention - Excessive smartphone use leads to several physical and psychological disorders, particularly among young adults. This study aimed to investigate the prevalence and the...     

Gut Hormones in Health and Obesity: The Upcoming Role of Short Chain Fatty Acids

We are currently facing an obesity pandemic, with worldwide obesity rates having tripled since 1975. Obesity is one of the main risk factors for the development of non-communicable diseases, which are now the leading cause of death worldwide. This calls for urgent action towards understanding the underlying mechanisms behind the development of obesity as well as developing more effective treatments and interventions. Appetite is carefully regulated in humans via the interaction between the central nervous system and peripheral hormones. This involves a delicate balance in external stimuli, circulating satiating and appetite stimulating hormones, and correct functioning of neuronal signals. Any changes in this equilibrium can lead to an imbalance in energy intake versus expenditure, which often leads to overeating, and potentially weight gain resulting in overweight or obesity. Several lines of research have shown imbalances in gut hormones are found in those who are overweight or obese, which may be contributing to their condition. Therefore, this review examines the evidence for targeting gut hormones in the treatment of obesity by discussing how their dysregulation influences food intake, the potential possibility of altering the circulating levels of these hormones for treating obesity, as well as the role of short chain fatty acids and protein as novel treatments.     

Vitamin D Status in Adolescents during COVID-19 Pandemic: A Cross-Sectional Comparative Study

Vitamin D has been claimed to be effective in the response to infections, including the respiratory syndrome coronavirus 2 (SARS-CoV-2). It is supposed that lockdown measures and fear of SARS-CoV-2 infection might reduce vitamin D levels through the modification of lifestyle. However, very few data exist on the association between lockdown measures and vitamin D status in humans. For this cross-sectional comparative study, adolescents (n = 298) aged 18 to 19 years were enrolled during the compulsory military fitness-for-duty evaluation between July and December 2020 in Southern Switzerland. Beyond anthropometric measurements, participants filled in a structured questionnaire about their lifestyle and a blood specimen was sampled for the determination of total 25-hydroxy-vitamin D. The obtained data were compared with those of 437 adolescents enrolled at the military fitness-for-duty evaluation during the same period of the year in the context of the CENERI study (2014–2016). The anthropometric measures were similar between the two study groups. The levels of vitamin D were also comparable (77 (64–91) vs. 74 (60–92) nmol/L, p = 0.50; median and interquartile range). A total of 38 (13%) and 43 (9.8%) subjects presented insufficient (<50 nmol/L) levels of vitamin D (p = 0.42) during the current pandemic and in the CENERI study, respectively. These data do not support the hypothesis that during the SARS-CoV-2 pandemic, late adolescents are at higher risk of vitamin insufficiency.     

Healthcare Cost Savings Associated with Increased Whole Grain Consumption among Australian Adults

Many dietary guidelines emphasise “mostly” whole grain food choices as part of an overall healthy eating pattern based on evidence for enhancing nutritional status and reducing chronic disease. Still, countries including Australia fall short of their consumption targets. Furthermore, healthcare cost savings associated with increasing the consumption of whole grains in alignment with the Daily Target Intake (DTI) recommendation of 48 g are unknown. The aim of this study was to assess the potential savings in costs of healthcare and lost productivity associated with a reduction in the incidence of Type 2 Diabetes Mellitus (T2DM) and cardiovascular disease (CVD) through meeting the 48 g DTI recommendation for whole grains among the Australian adult population (>20 years). A three-step cost-of-illness analysis was conducted using input parameters from: 1) estimates of proportions of consumers (5%, 15%, 50%, and 100%) who would increase their current intake of whole grains to meet the recommended DTI in Australia; 2) relative reductions in risk of T2DM and CVD associated with specific whole grain consumption, as reported in meta-analysis studies; and 3) data on costs of healthcare and productivity loss based on monetary figures by national healthcare authorities. A very pessimistic (5% of the population) through to universal (100% of the population) adoption of the recommended DTI was shown to potentially yield AUD 37.5 (95% CI 22.3–49.3) to AUD 750.7 (95% CI 445.7–985.2) million, and AUD 35.9 (95% CI 8.3–60.7) to AUD 717.4 (95% CI 165.5–1214.1) million in savings on annual healthcare and lost productivity costs for T2DM and CVD, respectively. Given such economic benefits of the recommended consumption of whole grains, in exchange for refined grains, there is a real opportunity to facilitate relevant socioeconomic cost-savings for Australia and reductions in disease. These results are suggestive of a much greater opportunity to communicate the need for dietary change at all levels, but particularly through food-based dietary guidelines and front-of-pack labelling initiatives.     

Evaluation of the effect of shift working and sleep quality on semen parameters in men attending infertility clinic

We aimed to evaluate the effect of shift work on semen parameters together with the effect of sleep quality in men attending infertility clinic. The participants were divided into two groups as follows: 104 shift worker men (Group 1) and 116 nonshift worker men (Group 2). Groups were compared in terms of semen parameters, Depression Anxiety Stress Scale-21 (DASS-21), and Pittsburg Sleep Quality Index (PSQI) scores. A higher rate of oligozoospermia and poor sleep quality and a lower mean normal morphology percentage was observed in shift workers than nonshift workers (p = .006, .039 and .036 respectively). In addition, a positive correlation was seen between sleep duration and sperm concentration, while a negative correlation was found between sleep latency and total sperm count. Shift working together with high PSQI score was also a significant association with oligozoospermia when controlling for the other variables of age, total testosterone, DASS-21 stress score, smoking and varicocele (OR = 2.11, 95% CI 1.03–4.34 and OR = 1.18, 95% CI 1.01–1.39 respectively). In this study, infertile shift workers had a lower percentage of normal morphology and higher rates of oligozoospermia and poor sleep quality. Considering that shift workers have lower sleep quality, it seems that shift working negatively affects the circadian rhythm.     

Hand Surgery in Different Countries: Hand Surgery in Saudi Arabia

Hand surgery is a unique field that incorporates multiple specialties, aiming to provide the patient with a best possible functional and aesthetic results. Hand surgeons deal with different pathologies that require skills in several aspects of surgery. The field of hand surgery has evolved significantly over the past decades across the globe. This specialty has also been evolving in Saudi Arabia over the past 25 years. Some of the services offered to patients include specialized centers for brachial plexus, peripheral nerve, and pediatric hand surgery as well as centers for work-related hand injuries. There has also been significant contribution to the hand surgery literature from the hand surgeons working in Saudi Arabia, with hundreds of papers published in journals pertaining to hand surgery, orthopedic surgery, and plastic surgery, as well as the publication of several novel mutations causing congenital hand defects in journals concerned with genetics. The recent approval of a hand and microsurgery fellowship program in Saudi Arabia will also help boost this field in the country and the region.