Comparison of KRAS gene in circulating tumor DNA levels vs histological grading of colorectal cancer patients through liquid biopsy.

Background: To determine KRAS gene in circulating tumor DNA in comparison with histological grading through liquid biopsy in colorectal cancer patients. Methods: This dual-centered cross-sectional study included 73 diagnosed patients of colorectal cancer at different grading levels [Grade I, well differentiated (n = 7, 9.5%); Grade II, moderately differentiated (n = 14,18.9%); and Grade III, poorly differentiated (n = 52, 70%)]. Blood was collected, and plasma was separated. ctDNA was extracted, using magnetic bead-based technique (MagMAX Cell-Free DNA kit). KRAS gene was quantified through qPCR. STRING database was used to find KRAS interactomes. Results: Mean threshold cycle (CT value) of KRAS gene in Grade III samples showed significantly higher (P = 0.001) levels of ctDNA (2.7 ± 1.14) compared with Grade II and Grade I (3.1 ± 0.68, 2.3 ± 0.60), respectively. Grading characterization showed that rectal cancer (n = 22, 42.3%) with Grade III (68.8%) was more prevalent than colon and sigmoid cancer (n = 19, 36.5%, n = 11, 21%, respectively). STRING database showed 10 functional genes interacting with KRAS expressed as gene/proteins. Conclusion: Liquid biopsy can be used to detect ctDNA in plasma of CRC patients and enabled to detect the KRAS gene by qPCR. The technique being less invasive and cost-effective is convenient for multiple biopsies in different cancers.

Venous Thromboembolism Among Hospitalized Patients: Incidence and Adequacy of Thromboprophylaxis - A Retrospective Study.

Purpose: We aimed to determine the incidence of venous thromboembolism among hospitalized patients in Qatar as well as to analyze the adequacy of VTE assessment and prophylaxis in hospitalized patients. Design: Retrospective observational study. Setting: Four hospitals under Hamad Medical Corporation, Qatar. Participants: Patients over the age of 18 who were hospitalized between January 2015 and December 2019 and developed venous thromboembolism during hospitalization or within a month after discharge were included. Results: During the study period, 641,994 individuals were admitted to hospitals. The inclusion criteria were satisfied by 209 of them. The mean age was 51.25 years and 54.5% were males. Hypertension and diabetes mellitus were the most common comorbidities found in the overall group. The incidence of VTE was 32.55 [95% CI 28.4, 37.3] per 100,000 admission per year [0.032%]. The annual incidence was least in 2015 (17.8 per 100,000 admissions) and highest in 2018 (44.4 per 100,000 admissions). Eighty-six subjects had DVT, and 109 had PE, whereas 14 had both. And, 67.5% of the patients developed VTE during admission while, 32.5% developed within 1 month of discharge. Moreover, 22.9% of the patients with PE developed pulmonary embolism after discharge from the hospital. VTE assessment was performed on 64.7% of the patients, and 69.7% received VTE prophylaxis in accordance with guidelines. Conclusion: Although the occurrence of VTE among hospitalized patients in Qatar is low, healthcare providers need additional education and knowledge of VTE assessment and prophylaxis to follow guidelines for all patients at the time of admission. Furthermore, risk assessment for VTE should be done for all patients at the time of discharge to decide on post-discharge prophylaxis so that incidence of VTE after discharge can be minimized. Future studies should focus on patients who developed VTE after discharge from the hospital as well as on various risk factors.

Evaluation of the Functional Treatment of Patients With Skeletal Class II Malocclusion Using Low-Level Laser Therapy-Assisted Twin-Block Appliance: A Three-Arm Randomized Controlled Trial.

Background Different techniques have been used to reduce functional treatment time including low-level laser therapy (LLLT), and the majority of studies have been conducted on animals. Therefore, the aim of the current study was to evaluate the effects of LLLT on improving orthodontic functional treatment using the Twin-Block (TB) appliance. Materials and methods This study was a three-arm, parallel-group randomized controlled trial. Patients were selected using the following inclusion criteria: skeletal Class II Division 1 malocclusion resulting from mandibular retrognathia (angle between the anterior cranial base and the NB plane (i.e., SNB angle): 73°-78°), the sagittal skeletal discrepancy angle (ANB angle) between 4° and 9°, and overjet between 5 and 9 mm. Forty-eight patients were randomly allocated into three equal groups. In the LLLT-TB group, the low-level laser device was used with a wavelength of 808 nm and power of 250 mW in addition to functional treatment with a Twin-Block appliance. The laser was applied on the skin at the bilateral temporomandibular joint (TMJ) regions, at five points, each point received 5 J of the laser for 20 seconds. The laser course was twice a week in the first month, every two weeks in the second month, and every three weeks up to the end of the treatment. The second group (the TB group) received functional treatment with a Twin-Block appliance, while patients in the third group (the untreated control group (UCG)) were observed for nine months without any intervention. Results There were statistically significant differences in treatment periods between the LLLT-TB group and the TB group (129 days and 235 days, respectively, P-value<0.001). The change in the effective mandibular length (Co-Gn) was the highest in the LLLT-TB group compared with the TB and the UCG groups (4.41 mm, 3.66 mm, and 1.07 mm, respectively; P-value<0.001). Conclusions The application of low-level laser therapy on the condylar regions accelerated the functional treatment in skeletal Class II malocclusion patients by approximately 45% and increased the bone growth and mandibular length. The improvement in the SNB angle was similar in both interventional groups. Irradiation of low-level laser stimulated bone growth at the condyles and did not cause anterior movement of the temporomandibular joint following functional orthopedic correction.

Waterpipe Tobacco Smoking and Other Multiple Sclerosis Environmental Risk Factors.

INTRODUCTION: There are a number of well-established risk factors for multiple sclerosis (MS). Other factors, however, showed conflicting or inconsistent results. Here, we examine some factors that are unique to or more practiced in Saudi Arabia (SA) and the Arab region such as waterpipe tobacco smoking (WTS), face veiling, raw milk (RM) and camel milk (CM) consumption, and tuberculosis (TB) infection in addition to other traditional factors. METHODS: This is a sex- and age-matched case-control study in which we used a structured questionnaire to examine the relation between a number of factors and exposures and the risk of MS. Three hundred MS patients and 601 controls were included. Data were analyzed across different statistical models using logistic regression adjusting for age, sex, marital status, duration of breastfeeding, age first joining school, coffee consumption, and face exposure. RESULTS: Cigarette smoking (OR = 1.79, [95% CI: 1.01-3.17], p = 0.047), WTS (OR = 2.25, [95% CI: 1.21-4.15], p = 0.010), and CM consumption (OR = 2.50, [95% CI: 1.20-5.21], p = 0.014) increased the risk of MS, while performing hajj (OR = 0.47, [95% CI: 0.34-0.67], p = 0.001), TB infection (OR = 0.29, [95% CI: 0.11-0.78], p = 0.015), face veiling (OR = 0.32, [95% CI: 0.23-0.47], p = 0.001), and coffee consumption (OR = 0.67, [95% CI: 0.49-0.89], p = 0.008) appeared to be associated with decreased risk. No association was found between fast food, processed meat, soft drinks, animal milk (other than camel), or RM consumption and the risk of MS. CONCLUSION: The results of this case-control study confirm that different means of tobacco smoking are associated with increased risk of MS. It also sheds more light on the complex association between infections and MS.

A novel, eco-friendly bio-nanocomposite (Alg-Cst/Kal) for the adsorptive removal of crystal violet dye from its aqueous solutions.

Herein, we report the synthesis of a novel bio-nanocomposite (Alg-Cst/Kal) for the effective removal of the dye "Crystal Violet" from its aqueous solutions. In order to observe the surface morphology and functional groups, the bio-nanocomposite was characterized using various techniques such as SEM, EDX, TEM, FTIR, XRD, and TGA. The effect of parameters like contact time, pH, concentration and temperature on the adsorption of the dye over adsorbent has been studied in detail. The dye - adsorbent system has been tested over various isotherm models and found to follow the Freundlich adsorption isotherm model at 303 K. The developed bio-nanocomposite material exhibits an excellent adsorption toward Crystal Violet with a maximum adsorption capacity of 169.49 mg.g-1. The experimental data has been further validated by applying various kinetic models and the pseudo-second order kinetic model was the best suited model. The calculated rate constant values ranged from 0.0046 to 0.0204 g.mg-1.min-1 for different dye concentrations. The positive values of change in enthalpy, ΔH° (9.765 kJ.mol-1) and change in entropy, ΔS° (0.0565 kJ.mol-1.K-1) obtained through thermodynamic studies demonstrate the endothermic nature and spontaneity of the adsorption process, respectively. The adsorption capacity of the adsorbent for the removal of the Crystal Violet dye was also compared with other adsorbents and found maximum. Novelty statement A novel bio-nanocomposite is synthesized by modifying the biopolymer alginate, cysteine and mixing the clay, kaolinite (Kal). The adsorption abilities of the material was tested the on the cationic hazardous dye, Crystal Violet. The material is novel and no attempt has so far been made to examine its batch adsorption abilities to remove hazardous dyes from the wastewater. The results are highly encouraging as out of all the adsorbents tested so far highest adsorption of the dye is observed in the present studies.

Shared breastfeeding & other early multiple sclerosis risk factors: A case-control study.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease. Etiology is thought to be multifactorial with genetic and environmental factors interplay. Our objective in this study is to evaluate culture specific and other early life risk factors for MS. We examined the association between MS and breastfeeding including shared breastfeeding, parental consanguinity, being born abroad or living abroad during childhood, prematurity, vaccination, tonsillectomy, rank among siblings, number of siblings, number of household members (HHM) at birth, and age first time joining school. METHODS: This is an age and sex matched case-control study that was conducted in Riyadh, Kingdom of Saudi Arabia (KSA). We enrolled 300 cases and 601 controls. A structured questionnaire about demographics, consanguinity and potential environmental factors was answered by participants. Data was analyzed using logistic regression adjusting for covariates occurring later in life such as waterpipe smoking and performing Hajj. RESULTS: About two thirds of the cases and the controls were females. Mean age was 34.8 (9.2) for the cases and 33.6 (10.6) for the controls. We found that shared breastfeeding (OR=0.58; 95% CI, 0.35-0.96, p = 0.033), and older age first joining school (OR=0.83; 95% CI, 0.73-0.94, p = 0.005) were associated with decrease risk of MS. While longer duration of breastfeeding by biological mother (OR=1.03; 95% CI, 1.01-1.04, p = 0.001), rank among siblings of ≥6 (OR=1.69; 95% CI, 1.11-2.56, p = 0.014), and larger number of HHM at birth (OR=2.32; 95% CI, 1.64-3.28, p = 0.001) were associated with increased risk. Patients with MS were less likely to receive formula with breastfeeding than controls (OR=0.72; 95% CI, 0.51-0.99, p = 0.046). No association was found with breastfeeding by biological mother, number of siblings, prematurity, being born abroad or living abroad during childhood, vaccination, consanguinity, or tonsillectomy. CONCLUSION: The findings of this case-control study add to the accumulating evidence that early life factors could modify the risk of developing MS. Among these, novel associations with shared breastfeeding and number of HHM at birth are suggested. Future studies are needed to verify the observed results.

Diagnostic Performance of Point-of-Care Troponin I and Laboratory Troponin T in Patients Presenting to the ED with Chest Pain: A Comparative Study.

BACKGROUND: Chest pain is a common symptom in patients visiting the emergency department (ED). Diagnosing acute coronary syndrome is a challenging task for emergency physicians. Evaluation of chest pain depends on clinical symptoms and signs, ECG, and cardiac enzymes. Here, we aimed to compare the diagnostic performance of the point-of-care troponin I assay with laboratory HsTnT assay in patients presenting to the ED with chest pain. METHODS: A prospective study was done at the ED of Alkhor Hospital, Hamad Medical Corporation, between March 2016 and December 2016. Patients more than 18 years old who presented to the ED with chest pain were enrolled. Patients with renal failure, initial ECG showing ST-elevation MI, or arrhythmias, and hemodynamically unstable patients were excluded. A blood sample was collected at 0 and 3 hours post-admission for POC TnI and laboratory HsTnT assay. The sensitivity, specificity, PPV, NPV, and AUC were determined and compared. RESULTS: Out of 313 patients enrolled, ten were excluded. At 0 hour, the POC TnI assay had a lower sensitivity (72.5% versus 97.5%) and had almost equal specificity (99.24% versus 93.2%) when compared to lab HsTnT assay. At 3 hours post-admission, the sensitivity increased to 95% versus 100%, and specificity was 100% versus 94.3% when compared to lab HsTnT. The POC TnI assay had a higher PPV than HsTnT, whereas both assays showed a high NPV at 0 and 3 hours. CONCLUSION: Although the diagnostic performance of POC TnI was lower than that of Lab HsTnT at 0 hour, at 3 hours post-admission, the diagnostic performance was almost equal to that of HsTnT. Hence we conclude that chest pain in patients with a negative POC TnI at 3 hours post-admission is unlikely to be due to NSTEMI.

Effects of low-intensity pulsed ultrasound (LIPUS) applied on the temporomandibular joint (TMJ) region on the functional treatment of class II malocclusion: A randomized controlled trial.

BACKGROUND: Low-intensity pulsed ultrasound (LIPUS) is considered one of the techniques used to improve the mandibular growth. Many animal studies have reported that significant results can be obtained using LIPUS therapy with functional appliances. OBJECTIVES: This research aimed to evaluate the dentoskeletal changes produced by the combination of LIPUS therapy and functional treatment during the correction of skeletal class II malocclusion. MATERIAL AND METHODS: Forty-five patients aged 10.5-14 years with skeletal class II division 1 malocclusion were randomly divided into 3 equal groups: the LIPUS group, treated with a Twin-Block appliance in combination with LIPUS therapy; the TB group, treated with a Twin-Block appliance only; and the control group, which was observational and received no treatment. Cephalometric changes were compared between the 3 groups using the analysis of variance (ANOVA) and Tukey's post hoc tests at p < 0.05. RESULTS: A greater significant decrease in the ANB (A point, nasion, B point) angle was observed in the treated groups (-2.67° for the LIPUS group and -2.11° for the TB group) as compared to the control group (p < 0.001). A greater improvement in the mandibular length and position was observed in the LIPUS group than in the TB group (p < 0.001). The changes in the control group as a result of continuing growth were minimal and clinically non-significant. CONCLUSIONS: The application of LIPUS therapy in combination with functional treatment can have a great effect on growth stimulation during the correction of class II malocclusion. In addition, LIPUS was effective in reducing the duration of functional treatment.

A Systematic Review of the Impact of Disaster on the Mental Health of Medical Responders.

INTRODUCTION: Medical responders are at-risk of experiencing a wide range of negative psychological health conditions following a disaster. AIM: Published literature was reviewed on the adverse psychological health outcomes in medical responders to various disasters and mass casualties in order to: (1) assess the psychological impact of disasters on medical responders; and (2) identify the possible risk factors associated with psychological impacts on medical responders. METHODS: A literature search of PubMed, Discovery Service, Science Direct, Google Scholar, and Cochrane databases for studies on the prevalence/risk factors of posttraumatic stress disorder (PTSD) and other mental disorders in medical responders of disasters and mass casualties was carried out using pre-determined keywords. Two reviewers screened the 3,545 abstracts and 28 full-length articles which were included for final review. RESULTS: Depression and PTSD were the most studied outcomes in medical responders. Nurses reported higher levels of adverse outcomes than physicians. Lack of social support and communication, maladaptive coping, and lack of training were important risk factors for developing negative psychological outcomes across all types of disasters. CONCLUSIONS: Disasters have significant adverse effects on the mental well-being of medical responders. The prevalence rates and presumptive risk factors varied among three different types of disasters. There are certain high-risk, vulnerable groups among medical responders, as well as certain risk factors for adverse psychological outcomes. Adapting preventive measures and mitigation strategies aimed at high-risk groups would be beneficial in decreasing negative outcomes.

Clusterin in atopic and non-atopic childhood asthma.

Several biomarkers have been studied to diagnose or to detect the phenotype of asthma. Clusterin is a sensitive cellular biosensor of oxidative stress and has been studied as a biomarker for inflammatory diseases. We aimed to study serum clusterin level in atopic versus non-atopic childhood asthma and its relation to disease severity. This case-control study included 160 children; 120 stable asthmatic children and 40 apparently healthy children. Asthmatic children were further subdivided into atopic and non-atopic. All children were subjected to medical history taking, clinical examination, and laboratory investigations including complete blood count, serum IgE, serum clusterin level and spirometry before and after bronchodilator therapy. In comparison to controls, patients had significantly higher eosinophils count which was higher in atopic than non-atopic group, also serum IgE level was higher in the atopic asthmatics (118.1 ± 16.2 U/ml) than in both the non-atopic asthmatics (81.2 ± 6.1 U/ml) and the controls (76.3 ± 11.6 U/ml). There was statistical significant difference in serum levels of Clusterin which were highest in the atopic group (182.5 ± 33.5 ng/l), followed by the non-atopic patients (127.5 ± 32.5 ng/l) and lowest in the controls (46.09 ± 7.01 ng/l). Moreover, the higher the severity of asthma, the higher was the level of serum clusterin. In conclusion serum level of clusterin was higher in atopic than non-atopic asthmatic children and it increases significantly with increased severity of the disease.

Supraphysiologic Testosterone Therapy in the Treatment of Prostate Cancer: Models, Mechanisms and Questions.

Since Huggins defined the androgen-sensitive nature of prostate cancer (PCa), suppression of systemic testosterone (T) has remained the most effective initial therapy for advanced disease although progression inevitably occurs. From the inception of clinical efforts to suppress androgen receptor (AR) signaling by reducing AR ligands, it was also recognized that administration of T in men with castration-resistant prostate cancer (CRPC) could result in substantial clinical responses. Data from preclinical models have reproducibly shown biphasic responses to T administration, with proliferation at low androgen concentrations and growth inhibition at supraphysiological T concentrations. Many questions regarding the biphasic response of PCa to androgen treatment remain, primarily regarding the mechanisms driving these responses and how best to exploit the biphasic phenomenon clinically. Here we review the preclinical and clinical data on high dose androgen growth repression and discuss cellular pathways and mechanisms likely to be involved in mediating this response. Although meaningful clinical responses have now been observed in men with PCa treated with high dose T, not all men respond, leading to questions regarding which tumor characteristics promote response or resistance, and highlighting the need for studies designed to determine the molecular mechanism(s) driving these responses and identify predictive biomarkers.

Dogs Have the Most Neurons, Though Not the Largest Brain: Trade-Off between Body Mass and Number of Neurons in the Cerebral Cortex of Large Carnivoran Species.

Carnivorans are a diverse group of mammals that includes carnivorous, omnivorous and herbivorous, domesticated and wild species, with a large range of brain sizes. Carnivory is one of several factors expected to be cognitively demanding for carnivorans due to a requirement to outsmart larger prey. On the other hand, large carnivoran species have high hunting costs and unreliable feeding patterns, which, given the high metabolic cost of brain neurons, might put them at risk of metabolic constraints regarding how many brain neurons they can afford, especially in the cerebral cortex. For a given cortical size, do carnivoran species have more cortical neurons than the herbivorous species they prey upon? We find they do not; carnivorans (cat, mongoose, dog, hyena, lion) share with non-primates, including artiodactyls (the typical prey of large carnivorans), roughly the same relationship between cortical mass and number of neurons, which suggests that carnivorans are subject to the same evolutionary scaling rules as other non-primate clades. However, there are a few important exceptions. Carnivorans stand out in that the usual relationship between larger body, larger cortical mass and larger number of cortical neurons only applies to small and medium-sized species, and not beyond dogs: we find that the golden retriever dog has more cortical neurons than the striped hyena, African lion and even brown bear, even though the latter species have up to three times larger cortices than dogs. Remarkably, the brown bear cerebral cortex, the largest examined, only has as many neurons as the ten times smaller cat cerebral cortex, although it does have the expected ten times as many non-neuronal cells in the cerebral cortex compared to the cat. We also find that raccoons have dog-like numbers of neurons in their cat-sized brain, which makes them comparable to primates in neuronal density. Comparison of domestic and wild species suggests that the neuronal composition of carnivoran brains is not affected by domestication. Instead, large carnivorans appear to be particularly vulnerable to metabolic constraints that impose a trade-off between body size and number of cortical neurons.

Higher stress scores for female medical students measured by the Kessler Psychological Distress Scale (K10) in Pakistan / 보건의료교육평가

The aim of this study was to determine the stress level of medical students and the relationship between stress and academic year. A cross-sectional, descriptive study was conducted at an undergraduate medical school with a five-year curriculum, in Pakistan, from January 2014 to April 2014. Medical students in the first four years were included in the study. The Kessler Psychological Distress Scale (K10), a self-administered questionnaire, was distributed to the students. A total of 445 medical students completed the questionnaire. The average stress score was 19.61 (SD=6.76) with a range from 10 to 43. Stress was experienced by 169 students (41.7%). The scores of female students were higher than scores of males, indicating a higher stress level (P=0.011). The relationship between stress and academic year was insignificant (P=0.392).

Distribution of Viruses Infecting Cucurbit Crops and Isolation of Potential New Virus-Like Sequences from Weeds in Oklahoma.

Field surveys were conducted from 2008 to 2010 to detect and determine the incidence of viruses in the major cucurbit-growing areas of Oklahoma. In total, 1,049 symptomatic leaf samples (890 from cucurbits, 109 from weed species, and 50 from crop plants [agricultural crops]) were collected from 90 fields in four counties (Atoka, Blaine, Jefferson, and Tulsa) of Oklahoma. Samples were tested against seven viruses, including Cucumber mosaic virus (CMV), Cucumber green mottle mosaic virus (CGMMV), Melon necrotic spot virus (MNSV), Papaya ringspot virus-watermelon strain (PRSV-W, formerly known as Watermelon mosaic virus-1), Squash mosaic virus (SqMV), Watermelon mosaic virus-2 (WMV-2), and Zucchini yellow mosaic virus (ZYMV), using dot-immunobinding assay (DIBA). Results showed the highest incidence for PRSV (51%), followed by WMV-2 (14%) and ZYMV (10%) among the collected samples. SqMV, MNSV, and CMV were detected in 3.8, 3.3, and 1.1% of the samples, respectively. None of the samples collected during surveys reacted positively against the antiserum of CGMMV. Mixed virus infections were common involving two (5.18%) or three (4.61%) viruses in various combinations. New weed host species were found to be infected with PRSV when confirmed by both DIBA and reverse-transcription polymerase chain reaction (RT-PCR). Some weed species contained possible new viruses when analyzed by random RT-PCR, followed by cloning, sequencing, and BLAST analysis with sequences in GenBank.