PTEN rs701848 Polymorphism is Associated with Trastuzumab Resistance in HER2-positive Metastatic Breast Cancer and Predicts Progression-free Survival.

BACKGROUND: Trastuzumab is an effective therapeutic approach for HER2-positive metastatic breast cancer (BC). However, a considerable number of patients develop resistance along the course of the disease. PTEN rs701848 polymorphisms are associated with an increased risk of developing cancer and have a potential role in predicting drug resistance. OBJECTIVE: We studied the significance of PTEN rs701848 variants as significant predictors for trastuzumab resistance in HER2-positive metastatic BC patients. Therefore, considering their value in predicting clinical outcomes. MATERIALS AND METHODS: This case-control study was conducted among female patients with HER2-positive metastatic breast cancer who underwent Trastuzumab therapy during the period from March 2017 to December 2020. PTEN rs701848 genotypes were analyzed in 160 HER2-positive metastatic breast cancer who received Trastuzumab therapy and clinically monitored for therapeutic response. RESULTS: PTEN rs701848 is deemed a significant predictor of Trastuzumab resistance and an independent prognostic factor of progression-free survival (PPFS). In particular, the C allele is associated with increased risk for Trastuzumab resistance and shorter PFS as compared to the homozygous TT genotype. CONCLUSION: PTEN rs701848 is significant predictor of trastuzumab resistance. Therefore, their value in predicting clinical outcomes is recommended.

Post-COVID-19 syndrome: assessment of short- and long-term post-recovery symptoms in recovered cases in Saudi Arabia.

INTRODUCTION: Recent studies investigated the endurance of symptoms and occurrence of complications three months after SARS-CoV-2 infection. This study aims to examine the prevalence, variation, and severity of continual symptoms in the post-COVID-19 using a single-center questionnaire. METHODS: The questionnaire was distributed among population in Saudi Arabia who recovered from COVID-19 between April 1, 2020 and December 31, 2021. RESULTS: A total of 744 participants completed the questionnaire, 318 (42.8%) recovered less than 3 months, 75 (10.1%) recovered 3-6 months, while 351 (47.2%) recovered more than 6 months. About half of the participants 353 (47.5%) had incessant symptoms and of those patients, more than half had two or more symptoms. Common symptoms included fatigue 189 (25.4%), headache 118 (15.9%), and myalgia 63 (8.5%). Of the participants, 189 (21.4%) experienced continual symptoms including anxiety in 98 (13.2%) and depression in 70 (9.5%). CONCLUSION: The current study showed a high proportion of individuals with long-COVID-19 symptoms. Thus, proper assessment of the individuals in the post-recovery period can guide the patients to the relevant clinics for rehabilitation. Moreover, there is a great importance to decrease COVID-19 infection, populations should be targeted to boost vaccine efficiency.

Incorporation of Pilates-based core strengthening exercises into the rehabilitation protocol for adolescents with patellofemoral pain syndrome: a randomized clinical trial.

OBJECTIVE: The objective of this study was to evaluate how a Pilates-based core strengthening exercise program affected pain, lower limb muscle strength, functional status, and health-related quality of life in adolescents with patellofemoral pain syndrome (PFPS). MATERIALS AND METHODS: In this randomized controlled clinical trial, 34 teenagers with PFPS (ages 14-17) were randomly assigned to receive either a standard PT program (control group) or Pilates exercises plus the conventional program (study group). Both groups continued the treatment sessions for 3 months (3 sessions/week). Pain intensity, lower limb muscle strength (hip abductors and external rotators and knee extensors), functional status, and health-related quality of life were evaluated pre-and post-intervention. RESULTS: Pain intensity (p =.005) reduced significantly post-treatment in the study group as compared to the control group, when controlled for the pre-treatment value. Also, muscle strength of hip abductors (p =.002) external rotators (p < .001), knee extensors (p = .013), functional status (p = .002), and health-related quality of life (p < .001) increased significantly in the study group when compared to the control group. CONCLUSIONS: The results of this study show that Pilates-based core strengthening exercises can help adolescents with PFPS reduce pain, enhance muscle strength, and improve their functional status and quality of life.

Correlation of Occupational Exposure to Carcinogenic Polycyclic Aromatic Hydrocarbons (cPAHs) and Blood Levels of p53 and p21 Proteins.

Carcinogenic polycyclic aromatic hydrocarbons (cPAHs) are considered the most serious cancer risk. This study was conducted to assess the effect of acute exposure to cPAHs on cancer biomarker proteins p53 and p21 in occupational workers during the hajj season in Makkah. One hundred five participants were recruited, including occupational workers and apparently healthy individuals; air samples were collected using personal sample monitors to identify the subjects' exposure to cPAHs. Quantitative analyses of benzo(a)anthracene (BaA), benzo(b)fluoranthene (BbF), benzo(a)pyrene (BaP), dibenzo(a,h)fluronathene (DBA), indeno(1,2,3-c,d)pyrene (IND) and chyresene (CRY) were carried out using the GC/Mass technique. Serum p53 and p21 proteins were analyzed using ELISA. The ambient air samples collected by the occupationally exposed group were more highly polluted by cPAHs, (90.25 ± 14.1) ng/m3, than those of the unexposed control groups, (30.12 ± 5.56) ng/m3. The concentration of distributive cPAHs was markedly more elevated in the air samples of the exposed group than in those taken from the non-exposed group. The study results demonstrated significant links between short-term exposure to cPAHs and serum p53 and p21 levels. Serum p53 and p21 proteins potentially influence biomarkers when exposed to ambient air cPAHs.

Correlation of COVID-19 Pandemic with Healthcare System Response and Prevention Measures in Saudi Arabia.

BACKGROUND: The Saudi government has taken the decision to prevent the entrance of about 2.5 million international pilgrims seeking to perform hajj in order to protect the world from a catastrophic widespread of disease. Moreover, health systems in Saudi Arabia are offering free testing for residents whether Saudi and non-Saudi. OBJECTIVE: This study aimed to evaluate the spread of COVID-19 associated with preventive measures taken in Saudi Arabia and to develop a detailed COVID-19 prevention strategy as a framework for the Saudi Arabia community. METHODOLOGY: Population size and age distributions among the country of Saudi Arabia were taken from the 2020 World Population Prospects. Contact patterns were measured using the Saudi Arabia Ministry of Health Statistical Annual Report. CONCLUSIONS: Our study demonstrates that performing screening tests as early as possible to facilitate the rapid detection of infected cases, fast treatment, and instant isolation for suspected cases is the most definitive rejoinder for public health. Moreover, our study revealed the significance of performing preventive measures in reducing infection and death rates around Saudi Arabia by 27%, while in other countries, it reduced the death rate ranging from 10-73%. This study provides an achievable strategy for prevention and early detection of COVID-19 spread.

Serum Levels of Selenium, Zinc, Copper, Manganese, and Iron in Prostate Cancer Patients.

BACKGROUNDS: Variations of trace element contents may be associated with several diseases including metabolic disorders, cellular growth disturbance, mutation and tumorigenesis. Prostate cancer is the second most common male cancer worldwide and stand fifth most common male cancer in Saudi Arabia. OBJECTIVE: In the present study, Serum levels of selenium, zinc, copper, manganese, and iron were measured in patients with BPH and prostate cancer aiming to explore the association between these elements and prostate cancer. PATIENTS AND METHODS: The study included 40 newly diagnosed prostate cancer patients, 22 patients with BPH and 30 healthy male subjects. All participant groups had similar socio-economic levels. Fasting blood samples were collected from all subjects and before any intervention for the patients. Serum PSA concentrations were analyzed by ELIZA and trace elements Se, Zn, Cu, Mn and Fe were measured by ICP-MS. RESULTS: Serum Se, Zn, and Mn levels of prostate cancer patients were significantly decreased compared to control groups. The levels of serum Cu and Fe were significantly higher in prostate cancer patients than in control groups. CONCLUSION: In the present study, an association was noticed between serum trace elements disturbance and prostate cancer. The decreased levels of Se, Zn, and Mn, and increased Cu and Fe levels may play significant roles in the initiation of prostate cancer. However, future prospective studies on the causes of trace elements alteration in prostate cancer patients are needed as well as to illustrate the relation between different prostate cancer stages and trace elements concentrations.

Trace Element Alterations in the Hair of Diabetic and Obese Women.

Alterations in the trace element content can induce metabolic disorders as these elements are involved in the regulation of metabolism. Obesity increases the likelihood of various diseases, particularly cardiovascular disease and type 2 diabetes, and is more prevalent in Saudi Arabia, especially in women. This study explored the potential of alterations in hair trace elements as long-term markers in diabetic and/or obese Saudi females. In total, 65 diabetic obese women, 47 non-diabetic obese women, and 70 normal-weight women were recruited. Clinical and familial history and anthropometric variables were recorded. Hair Se, Zn, Cu, Mn, and Fe levels were analyzed. Fasting blood sugar (FBS), glycated hemoglobin (HbA1c), and lipid profile were analyzed. Our findings revealed a marked decrease of hair Zn, Mn, and Fe and elevated Se and Cu levels in obese women. In addition, Zn and Fe levels were decreased in diabetic women. Thus, the metabolic distress occurring in obesity and hyperglycemia may affect trace element status by increasing the excretion and decreasing the bioavailability of trace elements or redistributing them among various pools. Hair trace elements can serve as important long-term markers for metabolic disorders; however, larger prospective studies are warranted to validate their diagnostic and follow-up utilities.

Quasi-empirical Bayes methodology for improving meta-analysis.

This article addresses the problem of heterogeneity among various studies to be combined in a meta-analysis. We adopt quasi-empirical Bayes methodology to predict the odds ratios for each study. As a result, the predicted odds ratios are pulled toward the estimated common odds ratio of the various studies under consideration. With strong heterogeneity among the studies, we jointly consider the display of the 95% CIs of the ORs and a Dixon's test (1950) for "outliers" to exclude the "extreme" estimated ORs. We demonstrate the effectiveness of our methodology based on the data analyzed by Thompson and Pocock (1987) demonstrating the power of the new approach to meta-analysis to find statistical agreement in what looks like great disagreement via a chi-squared test. We believe our technique (i.e., minimum mean-square sense) will go a long way toward increasing the trustworthiness of meta-analysis.

Maternal, amniotic fluid and cord blood metabolic profile in normal pregnant and gestational diabetics during recurrent withholding of food.

In order to advise regarding the religious practice of withholding food, we studied the metabolic changes after successive 15 days of recurrent fasting of 13 hours every day in maternal plasma and liquor amnii of obese normal gravids and gestational diabetics in their third trimester. There were no significant differences between those who fasted that period for one day prior to elective cesarean section (CS) and those who fasted the same period repeatedly for 15 days. The fasted gravids had significant rises in glycerol, beta-hydroxybutyrate (BOHB) and nonesterified fatty acids (NEFA) (P less than 0.0001, P less than 0.005 and P less than 0.01, respectively) in maternal plasma, compared to unfasted gravid groups and ungravid fasted group. No significant metabolic difference was found in the liquor amnii withdrawn from fasted and unfasted groups. The influence of such short term of starvation on the fetal metabolic profile was studied in the cord blood during cesarean section (CS). Glucose, glycerol and NEFA were significantly lower in arterial than in venous cord plasma (P less than 0.05, P less than 0.01 and P less than 0.01, respectively) indicating that the fetus could utilize these substrates. Positive correlation was found between the levels of BOHB in the mother and venous cord plasma on the one hand and their levels in the arterial cord plasma and liquor amnii on the other hand implying that this substrate passes unutilized through the fetus to the liquor amnii. A pregnant woman in the third trimester should not withhold food for long periods.

Postpartum glycated hemoglobin A1c and glucose tolerance test in mothers of large babies.

An attempt to study macrosomia and carbohydrate metabolism was made by determination of glycated hemoglobin A1c and by the oral glucose tolerance test (OGTT) in early puerperium. We studied 76 women who gave birth to large babies greater than or equal to 4.5 kg, 74 women whose babies were 3-4 kg as controls, and 36 type II diabetics. The median of HbA1c concentration in the diabetics (8.06%) was significantly higher than in the controls (6.49%), and the large babies' mothers (6.48%), P less than 0.001. No significant difference was found between HbA1c or glucose intolerance in mothers of large babies and mothers with average size babies. HbA1c showed an association with glucose levels in the diabetics and controls, P less than 0.001, but not in the large baby group. Mothers of large babies were as old and obese as the diabetics. We speculate that the relationship of postpartum GTT, HbA1c and gestational diabetes is unwarranted.

An automated liquid-chromatographic system for convenient determination of glycated hemoglobin A1c.

For quantification of glycated hemoglobin (HbA1c), we compared an automated system (Pharmacia Fast Protein Liquid Chromatography), which separates and determines HbA1c, with a commercial disposable-minicolumn kit (Boehringer-Mannheim), which separates total HbA1. We studied 41 diabetic women and 79 apparently normal women on their first postparturition day. The automated method was more precise (within-run CV 0.98-4.16%) than the kit method (within-run CV 3.67-7.77%). Results by the two methods correlated well for both control (p less than 0.001) and diabetic (p less than 0.05) groups. Values for HbA1c correlated significantly with fasting blood-glucose concentrations in controls and diabetics (intraclass correlation coefficient rI = 0.822 and 0.851, respectively, p less than 0.001) as well as with 1- and 2-h values for glucose after a 75-g glucose load in the control group (rI = 0.649 and 0.846, respectively, p less than 0.001). For HbA1 no such significant correlation was found except with values for fasting blood glucose in diabetics (rI = 0.745, p less than 0.001). Evaluation of HbA1c was a more sensitive index of glycemic status. The automated system is convenient, reliable, and easily operated.

Influence of pregnancy outcome on subsequent pregnancy.

In this study to determine the harmful effect of abnormal pregnancy outcome on the immediately following pregnancy, 573 recently delivered women (with 2347 pregnancies) were interviewed. Data were recorded on their pregnancy outcomes (normal, abortion, stillbirth and congenital malformation), as well as on their interpregnancy intervals. A significant difference was found between the chances of having a spontaneous abortion following a normal outcome (5.5%) against that following a spontaneous abortion (31.1%). Also, the chances of a normal outcome following a normal outcome were 92.4%, compared with 63.9% following a spontaneous abortion. The delivery of a malformed baby is associated with a larger proportion of abortion and congenital malformation in the subsequent pregnancy, while stillbirth was followed by a larger proportion of abortion and stillbirth. A longer interpregnancy interval did not appear to have any protective effect on the subsequent pregnancy.

PIP: In this study to determine the harmful effect of abnormal pregnancy outcome on the immediately following pregnancy, 573 recently delivered Kuwati women (with 2347 pregnancies) were interviewed. Data were recorded on their pregnancy outcomes (normal, abortion, stillbirth and congenital malformation), as well as on their interpregnancy intervals. A significant difference was found between the chances of having a spontaneous abortion following a normal outcome (5.5%) against that following a spontaneous abortion (31.1%). Also, the chances of a normal outcome following a normal outcome were 92.4%, compared with 63.9% following a spontaneous abortion. The delivery of a malformed baby is associated with a larger proportion of abortion and congenital malformation in the subsequent pregnancy, while stillbirth was followed by a larger proportion of abortion and stillbirth. The etiologic mechanisms are still largely speculative, including the trophoblastic rest and other hypotheses, although some authorities have already adopted the precautionary measure of advising their patients following a spontaneous abortion to delay the next pregnancy. A longer interpregnancy interval did not appear to have any protective effect on the subsequent pregnancy.