Characteristics and outcomes of large artery occlusion-related stroke due to intracranial atherostenosis: An experience from a single center in Saudi Arabia.

BACKGROUND: Literature on the frequency, response to treatment, and outcomes of acute ischemic stroke (AIS) due to intracranial atherostenosis (ICAS)-related intracranial large artery occlusion (ILAO) from Saudi Arabia is scarce. The aim of this study was to identify the percentage, describe the characteristics, and observe the treatment response in patients with AIS attributed to ICAS-related ILAO. MATERIALS AND METHODS: This cross-sectional study included all adult patients from 2017-2021 who fulfilled the inclusion criteria for the diagnosis of ICAS-related AIS. Patients were dichotomized based on ILAO. Mortality and functional outcomes (FOCs) based on 90 days' dependence level were compared between the two groups. The association between ILAO and other variables was assessed using the Chi-squared test, odds ratios (OR), and 95% confidence interval (CI). RESULTS: ILAO was found in 38.7% of patients with ICAS-related AIS. Men comprised three-fourths of the cohort and were more frequent in the ILAO group. Smoking was associated with increased (P = 0.04) likelihood of ILAO. Patients with ILAO had more severe strokes (P ≤ 0.001) than patients without. Middle cerebral artery was the most common occluded vessel (52%). Functional dependence (P = 0.003, OR = 2.87, CI = 1.42-5.77), malignant transformation (P = 0.001, OR = 8.0, CI = 1.82-35.9), and mortality (P ≤ 0.001, OR = 7.67, CI = 2.40-24.5) were significantly higher among ILAO group. Patients with ILAO with unfavorable FOC were older than those who achieved better FOC (P ≤ 0.001). Thrombolysis (P = 0.02, OR = 2.50, CI = 1.15-5.41) and mechanical thrombectomy (MT) improved FOC in patients with ILAO (P = 0.04, OR = 2.33, CI = 1.10-4.92). CONCLUSION: ILAO is common in patients with ICAS-related AIS. Timely hyperacute stroke treatment can help improve the FOC of otherwise disabling stroke due to ILAO. Raising awareness of the community about stroke is needed, so that a higher number of patients can arrive at hospital within the golden hours. Further data from the region are required to recognize the efficacy of MT in ICAS-related ILAO.

Thiol-disulfide homeostasis in irritable bowel syndrome.

OBJECTIVE: The etiopathogenesis and pathophysiological mechanism of irritable bowel syndrome (IBS) is not fully known. In this study, evaluating dynamic thiol-disulfide homeostasis (TDH) in patients with IBS was aimed. SUBJECTS AND METHODS: A total of 92 people, 46 IBS patients and 46 healthy sex and aged-matched volunteers, were included in the study. Thiol/disulfide parameters in serum were measured in all cases, and the two groups were compared. RESULTS: Disulfide levels (21.9 ± 5.0 µmol/L vs. 19.4 ± 4.2 µmol/L, respectively; p < 0.001), disulfide/native thiol (5.7%  ± 1.2% vs. 4.9% ± 0.8%, p < 0.001, respectively) and disulfide/total thiol ratio (5.1% ± 0.9% vs. 4.5% ± 0.7%, respectively, p < 0.001) were found to be higher in IBS patients, and native thiol/total thiol ratio (89.8% ± 1.9%, 90.6% ± 1.9%, p < 0.001, respectively) was found to be lower in IBS patients. CONCLUSIONS: In our study, it was shown that TDH is impaired in IBS, which is an important result supporting studies showing that oxidative stress plays a role in IBS. On the other hand, it is thought that this study will contribute to the literature in terms of being the first study evaluating TDH in adult IBS.

A spatially specified systems pharmacology therapy for axonal recovery after injury.

There are no known drugs or drug combinations that promote substantial central nervous system axonal regeneration after injury. We used systems pharmacology approaches to model pathways underlying axonal growth and identify a four-drug combination that regulates multiple subcellular processes in the cell body and axons using the optic nerve crush model in rats. We intravitreally injected agonists HU-210 (cannabinoid receptor-1) and IL-6 (interleukin 6 receptor) to stimulate retinal ganglion cells for axonal growth. We applied, in gel foam at the site of nerve injury, Taxol to stabilize growing microtubules, and activated protein C to clear the debris field since computational models predicted that this drug combination regulating two subcellular processes at the growth cone produces synergistic growth. Physiologically, drug treatment restored or preserved pattern electroretinograms and some of the animals had detectable visual evoked potentials in the brain and behavioral optokinetic responses. Morphology experiments show that the four-drug combination protects axons or promotes axonal regrowth to the optic chiasm and beyond. We conclude that spatially targeted drug treatment is therapeutically relevant and can restore limited functional recovery.

A high rate of post thrombotic complication in pediatric portal vein thrombosis.

INTRODUCTION: Portal vein thrombosis (PVT) is a rare disease in children and may be complicated by portal hypertension (PH), hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPHTN) but their incidence and risk factors are unknown. METHODS: An observational, retrospective cohort study of all consecutive children (≤18 years) with PVT treated at the Emma Children's Hospital Amsterdam University Medical Centers between January 1996 and January 2022 was conducted to identify the incidence and risk factors of these post thrombotic complications (PTC) in pediatric patients. RESULTS: In total 43/ 703 thrombosis patients had PVT (boys 72.1 %; mean age 1.3 ± 0.5 years). Overall, 51 % of patients developed PH (n = 22), complicated by PPHTN in one of them. In 16 of 22 patients, PVT presented with portal hypertension. Clinically relevant bleeding due to portal hypertension occurred in 13 (59.1 %) patients with PH. The mean age at the first clinically relevant bleeding was 5.1 ± 5.9 years. Risk factors for the development of PH were lack of complete thrombus resolution (OR 24.3, 95 % CI 1.2-7.0; p = 0.008) and unprovoked VTE (OR, 35.4; 95 % CI 1.4-6.3; p = 0.012). Median time from PVT to PH was 137 days (range: 0 days to 5.04 years). CONCLUSION: We demonstrated that half of the patients develop PH after PVT, with a lack of thrombus resolution and unprovoked VTE as independent risk factors. This high incidence underlines the importance of long-term standardized follow-up of patients after PVT and standard screening in patients at risk of PTC.

Scapholunate Ligament Partial Tears; Tear Localization, Extrinsic Ligament Injury Association and Conservative Treatment Responses Prior to Instability: Cross-Sectional Study.

PURPOSE OF THE STUDY Scapholunate interosseous ligament (SLIOL) tears with accompanying extrinsic ligament rupture have been associated with scapholunate (SL) instability. SLIOL partial tears were examined in terms of tear localization, grade and accompanying extrinsic ligament injury. Conservative treatment responses were scrutinized according to injury types. MATERIAL AND METHODS Patients with SLIOL tear without dissociation were evaluated retrospectively. Magnetic resonance (MR) images were reexamined in terms of tear localization (volar, dorsal or combined volar and dorsal tears), grade of injury (partial or complete) and extrinsic ligament injury accompaniment (RSC, LRL, STT, DRC, DIC). Injury associations were examined with MR imaging. All patients treated conservatively were recalled at their first year for re-evaluation. Conservative treatment responses were analyzed according to pre- and post-treatment first year visual analog scale for pain (VAS), disabilities of the arm, shoulder and hand questionnaire (DASH) and Patient-Rated Wrist Evaluation (PRWE) scores. RESULTS In our cohort, 79% (n: 82/104) of patients had SLIOL tear and 44% (n: 36) of them had accompanying extrinsic ligament injury. The majority of SLIOL tears and all extrinsic ligament injuries were partial tears. In SLIOL injuries, volar SLIOL was most commonly damaged portion (45%, n: 37). DIC (n: 17) and LRL (n: 13) were most frequently torn ligaments, radiolunotriquetral (LRL) injury generally co-existed with volar tears and dorsal intercarpal ligament (DIC) with dorsal tears regardless of injury time. Extrinsic ligament injury accompaniment was associated with higher pre-treatment VAS, DASH and PRWE scores than isolated SLIOL tears. Injury grade, location and extrinsic ligament accompaniment had no significant effect on treatment responses. Test scores reversal was better in acute injuries. CONCLUSIONS On imaging SLIOL injuries, attention should be paid to the integrity of secondary stabilizers. In partial SLIOL injuries, pain reduction and functional recovery can be achieved with conservative treatment. Conservative approach can be the initial treatment option in partial injuries especially in acute cases regardless of tear localization and injury grade if secondary stabilizers are intact. Key words: scapholunate interosseous ligament, extrinsic wrist ligaments, carpal instability, MRI of wrist, wrist ligamentous injury, volar and dorsal scapholunate interosseous ligament.

Determinants of quality of life of cancer patients at a tertiary care medical city in Riyadh, Saudi Arabia.

Background: Incidences of cancer are increasing at an unprecedented rate in Saudi Arabia, making it a major public health concern. Cancer patients are faced with physical, psychological, social, and economic challenges, all of which can impact quality of life (QoL). Objectives: This study aims to explore the sociodemographic, psychological, clinical, cultural, and personal factors that could affect the overall QoL of cancer patients. Methods: A total of 276 cancer patients who attended the King Saud University Medical City's oncology outpatient clinics between January 2018 to December 2019 were included. QoL was assessed with the Arabic version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30. Psychosocial factors were assessed with several validated scales. Results: QoL was poorer among patients who were female (p = 0.001), have visited a psychiatrist (p = 0.028); were taking psychiatric medications (p = 0.022); and had experienced anxiety (p < 0.001), depression (p < 0.001), and distress (p < 0.001). The most used method to self-treat was Islamic Ruqya (spiritual healing; 48.6%), and the most often perceived cause for developing cancer was evil eye or magic (28.6%). Good QoL outcomes were associated with biological treatment (p = 0.034) and satisfaction with health care (p = 0.001). A regression analysis showed that female sex, depression, and dissatisfaction with health care were independently associated with poor QoL. Conclusions: This study demonstrates that several factors could influence cancer patients' QoL. For instance, female sex, depression, and dissatisfaction with health care were all predictors of poor QoL. Our findings support the need for more programs and interventions to improve the social services for cancer patients, along with the need to explore the social difficulties oncology patients face and address such obstacles through improving social services by expanding the scope of social workers' contribution. Larger multicenter longitudinal studies are warranted to examine the generalizability of the results.

Expanding the knowledge around antitubercular 5-(2-aminothiazol-4-yl)isoxazole-3-carboxamides: Hit-to-lead optimization and release of a novel antitubercular chemotype via scaffold derivatization.

Tuberculosis is one of the deadliest infectious diseases in the world, and the increased number of multidrug-resistant and extensively drug-resistant strains is a reason for concern. We have previously reported a series of substituted 5-(2-aminothiazol-4-yl)isoxazole-3-carboxamides with growth inhibitory activity against Mycobacterium tuberculosis strains and low propensity to be substrate of efflux pumps. Encouraged by these preliminary results, we have undertaken a medicinal chemistry campaign to determine the metabolic fate of these compounds and to delineate a reliable body of Structure-Activity Relationships. Keeping intact the (thiazol-4-yl)isoxazole-3-carboxamide core, as it is deemed to be the pharmacophore of the molecule, we have extensively explored the structural modifications able to confer good activity and avoid rapid clearance. Also, a small set of analogues based on isostere manipulation of the 2-aminothiazole were prepared and tested, with the aim to disclose novel antitubercular chemotypes. These studies, combined, were instrumental in designing improved compounds such as 42g and 42l, escaping metabolic degradation by human liver microsomes and, at the same time, maintaining good antitubercular activity against both drug-susceptible and drug-resistant strains.

Myelin-associated glycoprotein alters the neuronal secretome and stimulates the release of TGFß and proteins that affect neural plasticity.

Myelin-associated glycoprotein (MAG) and Nogo inhibit neurite outgrowth by binding to receptors such as NgR1, PirB and LRP1, and they have also been shown to induce phosphorylation of Smad2, a key intermediate in the transforming growth factor ß (TGFß) signalling pathway. In this study, we determined that MAG and Nogo do not transactivate the TGFß receptor through their canonical receptors or discoidin domain receptor 1, which we identified as a novel receptor for MAG and Nogo. Instead, MAG and Nogo promoted Smad2 phosphorylation by stimulating secretion of TGFß. Proteomic analysis of the neuronal secretome revealed that MAG also regulated the secretion of proteins that affect central nervous system plasticity-inducing the secretion of S100A6, septin-7 and neurofascin 186, while inhibiting the secretion of frataxin, MAP6, syntenin-1 and GAP-43. This represents a novel function for MAG that has broad implications for the treatment for spinal cord injury.

Prevalence of Anemia Among Children and Adolescents in Rural Area of Khulais in Saudi Arabia.

Introduction The decreased absolute circulating red blood cell count or the inability of red blood cells to meet physiological needs is called anemia. Anemia can affect mental health, learning capacity, and the ability to concentrate. The present study aimed to assess the prevalence of anemia among children and adolescents living in the rural areas of Khulais, Saudi Arabia. Methods This cross-sectional study including 417 individuals was conducted at Khulais Hospital in the rural areas in Saudi Arabia to estimate the prevalence of anemia among children and adolescents. The inclusion criterion for the study was that participants must be Saudi citizens. Data for this study were collected in March 2021. The age of the children ranged from 7 to 11 years, whereas that of adolescent males and females was between 12 and 18 years. Results In total, the study included 147 male adolescents, 123 female adolescents, and 147 children participants. The overall prevalence of anemia among adolescents was high (39.1%). The prevalence of anemia was 44.9% (66/147), 46.3% (57/123), and 27.2% (40/147) in male adolescents (age 12-18 years), female adolescents (age 12-18 years), and children (age 7-11 years), respectively. Statistical analysis revealed an association between the prevalence of anemia and the increasing age of participants from rural areas. Conclusion The present study results indicate that the prevalence of anemia in the rural areas of Saudi Arabia is high. The high prevalence can be explained by several factors, such as parents' low socioeconomic status and living in rural areas, which limits the availability as well as different types of nutritious food and thereby negatively affects the nutritional status of such children and adolescents.

Working from within: how secretory leukocyte protease inhibitor regulates the expression of pro-inflammatory genes.

Secretory leukocyte protease inhibitor (SLPI) is a small but powerful member of the serine protease inhibitor family, which includes proteins such as elafin and α1-antitrypsin. These proteins all have similar structures and antiprotease abilities, but SLPI has been found to have an additional role as an anti-inflammatory factor. It can inhibit the production of pro-inflammatory cytokines in cells stimulated with lipopolysaccharide, prevent neutrophil infiltration in murine models of lung and liver injury, and regulate the activity of the transcription factor NF-κB. In this review, we will revisit SLPI's unique biochemistry, and then explore how its anti-inflammatory functions can be linked to more recent findings showing that SLPI can localize to the nuclei of cells, bind DNA, and act as a regulator of gene expression.

Novel 2,4-disubstituted quinazoline analogs as antibacterial agents with improved cytotoxicity profile: Optimization of the 2,4-substituents.

The emergence of bacterial resistance has triggered a multitude of efforts to develop new antibacterial agents. There are many compounds in literature that were reported as potent antibacterial agents, however, they lacked the required safety to mammalian cells or no clear picture about their toxicity profile was presented. Inspired by discovered hit from our in-house library and by previously reported 2,4-diaminosubstituted quinazolines, we describe the design and synthesis of novel 2,4-disubstituted-thioquinazolines (3-13 and 36), 2-thio-4-amino substituted quinazolines (14-33) and 6-substituted 2,4-diamonsubstituted quinazolines (37-39). The synthesized compounds showed potent antibacterial activity against a panel of Gram-positive, efflux deficient E.coli and Mycobacterium smegmatis. The panel also involved resistant strains including methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae, vancomycin-resistant Enterococcus faecalis and vancomycin-resistant Enterococcus faecium, in addition to Mycobacterium smegmatis. The newly synthesized compounds revealed MIC values against the tested strains ranging from 1 to 64 µg/mL with a good safety profile. Most of the 2-thio-4-amino substituted-quinazolines showed significant antimycobacterial activity with the variations at position 2 and 4 offering additional antibacterial activity against the different strains. Compared to previously reported 2,4-diaminosubstituted quinazolines, the bioisosteric replacement of the 2-amino with sulfur offered a successful approach to keep the high antibacterial potency while substantially improving safety profile as indicated by the reduced activity on different cell lines and a lack of hemolytic activity.

Computationally grafting an IgE epitope onto a scaffold: Implications for a pan anti-allergy vaccine design.

Allergy is becoming an intensifying disease among the world population, particularly in the developed world. Once allergy develops, sufferers are permanently trapped in a hyper-immune response that makes them sensitive to innocuous substances. The immune pathway concerned with developing allergy is the Th2 immune pathway where the IgE antibody binds to its Fc ∊ RI receptor on Mast and Basophil cells. This paper discusses a protocol that could disrupt the binding between the antibody and its receptor for a potential permanent treatment. Ten proteins were computationally designed to display a human IgE motif very close in proximity to the IgE antibody's Fc ∊ RI receptor's binding site in an effort for these proteins to be used as a vaccine against our own IgE antibody. The motif of interest was the FG loop motif and it was excised and grafted onto a Staphylococcus aureus protein (PDB ID 1YN3), then the motif + scaffold structure had its sequence re-designed around the motif to find an amino acid sequence that would fold to the designed structure correctly. These ten computationally designed proteins showed successful folding when simulated using Rosetta's AbinitioRelax folding simulation and the IgE epitope was clearly displayed in its native three-dimensional structure in all of them. These designed proteins have the potential to be used as a pan anti-allergy vaccine. This work employedin silicobased methods for designing the proteins and did not include any experimental verifications.

Inhibition of Autophagy Flux Promotes Secretion of Chondroitin Sulfate Proteoglycans in Primary Rat Astrocytes.

Following spinal cord injury (SCI), reactive astrocytes in the glial scar produce high levels of chondroitin sulfate proteoglycans (CSPGs), which are known to inhibit axonal regeneration. Transforming growth factor beta (TGFß) is a well-known factor that induces the production of CSPGs, and in this study, we report a novel mechanism underlying TGFß's effects on CSPG secretion in primary rat astrocytes. We observed increased TGFß-induced secretion of the CSPGs neurocan and brevican, and this occurred simultaneously with inhibition of autophagy flux. In addition, we show that neurocan and brevican levels are further increased when TGFß is administered in the presence of an autophagy inhibitor, Bafilomycin-A1, while they are reduced when cells are treated with a concentration of rapamycin that is not sufficient to induce autophagy. These findings suggest that TGFß mediates its effects on CSPG secretion through autophagy pathways. They also represent a potential new approach to reduce CSPG secretion in vivo by targeting autophagy pathways, which could improve axonal regeneration after SCI.

Dramatic rapid recovery after transcathater aortic valve implantation in patient with ischemic hepatitis and hyperbilirunemia.

Transcatheter aortic valve implantation (TAVI) is widely used in high-risk patients with severe symptomatic aortic valve stenosis (AS). The use of traditional surgical aortic valve replacement (SAVR) significantly increases the risk of complications in chronic liver failure with the release of many vasoactive and cytotoxic substrates. In patients with ischemic hepatitis or liver dysfunction along with the severe AS, TAVI may be advantageous due to its minimally invasive nature. However, there is limited information about the outcome of TAVI in a patient with both hepatic and multisystem dysfunction. We report this case demonstrating dramatic result of TAVI in a patient in extremely poor clinical condition due to ischemic hepatitis and hyperbilirunemia.

Extracellular histones, a new class of inhibitory molecules of CNS axonal regeneration.

Axonal regeneration in the mature CNS is limited by extracellular inhibitory factors. Triple knockout mice lacking the major myelin-associated inhibitors do not display spontaneous regeneration after injury, indicating the presence of other inhibitors. Searching for such inhibitors, we have detected elevated levels of histone H3 in human CSF 24 h after spinal cord injury. Following dorsal column lesions in mice and optic nerve crushes in rats, elevated levels of extracellular histone H3 were detected at the injury site. Similar to myelin-associated inhibitors, these extracellular histones induced growth cone collapse and inhibited neurite outgrowth. Histones mediate inhibition through the transcription factor Y-box-binding protein 1 and Toll-like receptor 2, and these effects are independent of the Nogo receptor. Histone-mediated inhibition can be reversed by the addition of activated protein C in vitro, and activated protein C treatment promotes axonal regeneration in the crushed optic nerve in vivo. These findings identify extracellular histones as a new class of nerve regeneration-inhibiting molecules within the injured CNS.

Combination therapy with TiO2 nanoparticles and cisplatin enhances chemotherapy response in murine melanoma models.

BACKGROUND: Despite recent progressions in the treatment of melanoma, the response to conventional therapies and the long-term survival in melanoma patients still remain poor. Recently, the use of nanoparticles (NPs) has been highlighted for promoting the chemotherapeutic effects of cytotoxic drugs in melanoma. The aim of this study is to mechanistically evaluate the potential of titanium dioxide (TiO2) nanoparticles (NPs) for enhancing chemotherapy effects in in vitro and in vivo models of murine melanoma. METHODS: The F10 melanoma cells were exposed to different concentrations of TiO2 NPs and/or cisplatin, then cell growth, cell viability, and cell death were evaluated. In parallel, C57BL/6 syngeneic melanoma mice were treated by TiO2 NPs and/or cisplatin, and then drug responses, tumor size and mice's organs were studied pathologically. Autophagy was examined by evaluating the formation of autophagosomes and gene expression levels of autophagy markers (ATG5 and ATG6) by fluorescent microscopy and qPCR, respectively. RESULTS: Nontoxic concentrations of TiO2 NPs (50 µg/ml) promote anti-proliferative and cytotoxic effects of cisplatin in F10 melanoma cells, which is mediated through the induction of autophagy and necrotic cell death. Whereas TiO2 NPs have no cytotoxic or metastatic effects in melanoma mice, its combination with cisplatin enhances drug responses (up to 50%), leading to higher inhibition of tumor growth compared with each monotherapy. CONCLUSION: The combination of TiO2 NP with cisplatin enhances chemotherapy response in both in vitro and in vivo melanoma models. In addition, autophagy plays an essential role during sensitizing melanoma cells to chemotherapy.

Risk factors for post-ERCP pancreatitis: it depends on the ERCP indication.

BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is an invasive modality, and has a high risk of causing post-ERCP pancreatitis (PEP). Risk factors of PEP have been investigated and conflicting results are present for most risk factors. The aim of this study was to evaluate the risk factors for PEP and to determine whether the risk factors differ due to the ERCP indication. PATIENTS AND METHODS: A retrospective study was conducted which included 666 patients with 968 ERCP procedures. Some risk factors were evaluated for PEP, and they were also evaluated separately for patients with bile duct stones and patients who underwent ERCP for other reasons than bile duct stones. RESULTS: In patients with bile duct stones detected on ERCP ; female gender, lower diameter of the common bile duct, placing a biliary plastic stent and not having a cholecystectomy history were risk factors for PEP, whereas in patients without bile duct stones the only risk factor for PEP was not having a prior endoscopic sphincterotomy. CONCLUSIONS: Our study revealed that PEP risk factors depend on the indication of ERCP. To the best of our knowledge our study is the first study defining cholecystectomy as a protective factor for PEP in patients with bile duct stones and endoscopic sphincterotomy history as a protective factor for PEP in patients without bile duct stones. Our study also showed that female gender, lower diameter of the common bile duct and placing a plastic biliary stent were risk factors for PEP in patients with bile duct stones.

Interaction between the genetic risk score and dietary protein intake on cardiometabolic traits in Southeast Asian.

BACKGROUND: Cardiometabolic diseases are complex traits which are influenced by several single nucleotide polymorphisms (SNPs). Thus, analysing the combined effects of multiple gene variants might provide a better understanding of disease risk than using a single gene variant approach. Furthermore, studies have found that the effect of SNPs on cardiometabolic traits can be influenced by lifestyle factors, highlighting the importance of analysing gene-lifestyle interactions. AIMS: In the present study, we investigated the association of 15 gene variants with cardiometabolic traits and examined whether these associations were modified by lifestyle factors such as dietary intake and physical activity. METHODS: The study included 110 Minangkabau women [aged 25-60 years and body mass index (BMI) 25.13 ± 4.2 kg/m2] from Padang, Indonesia. All participants underwent a physical examination followed by anthropometric, biochemical and dietary assessments and genetic tests. A genetic risk score (GRS) was developed based on 15 cardiometabolic disease-related SNPs. The effect of GRS on cardiometabolic traits was analysed using general linear models. GRS-lifestyle interactions on continuous outcomes were tested by including the interaction term (e.g. lifestyle factor*GRS) in the regression model. Models were adjusted for age, BMI and location (rural or urban), wherever appropriate. RESULTS: There was a significant association between GRS and BMI, where individuals carrying 6 or more risk alleles had higher BMI compared to those carrying 5 or less risk alleles (P = 0.018). Furthermore, there were significant interactions of GRS with protein intake on waist circumference (WC) and triglyceride concentrations (Pinteraction = 0.002 and 0.003, respectively). Among women who had a lower protein intake (13.51 ± 1.18% of the total daily energy intake), carriers of six or more risk alleles had significantly lower WC and triglyceride concentrations compared with carriers of five or less risk alleles (P = 0.0118 and 0.002, respectively). CONCLUSIONS: Our study confirmed the association of GRS with higher BMI and further showed a significant effect of the GRS on WC and triglyceride levels through the influence of a low-protein diet. These findings suggest that following a lower protein diet, particularly in genetically predisposed individuals, might be an effective approach for addressing cardiometabolic diseases among Southeast Asian women.

Natural products and polysorbates: Potential Inhibitors of biofilm formation in Pseudomonas aeruginosa.

INTRODUCTION: With all the challenges super bugs are imposing, biofilm formation opens the door against various more complicated challenges. Such issue may be highlighted with the ability of the latter to render the antibiotics hardly accessible to bacterial cells and sheds the light on the importance of finding antibiofilm formers. Therefore, we assessed the inhibitory effect of natural product extracts (ginger, wild blueberry) and polysorbates (PS20, PS80) on biofilm formation at the molecular level. METHODOLOGY: Growth inhibition assay was performed to test the effect of ginger (Zingiber Officinale), wild blueberry (Vaccinium Angustifolium), and polysorbates on Pseudomonas aeruginosa (PAN14) growth. Transcription levels of biofilm exopolysaccharides encoding genes (ndvB, pelC, algC) and quorum sensing genes (lasI, lasR, rhlI, rhlR) for LasI/LasR and RhlI/ RhlR systems were evaluated by RT qPCR. RESULTS: The polysorbates and the extracts of both ginger and wild blueberry had no effect on the growth of P. aeruginosa. Biofilms' examination has unraveled the effectiveness of treatments used in reducing its formation. Moreover, a significant reduction in the expression of all genes tested for biofilm exopolysaccharides and its quorum sensing system was observed. CONCLUSION: The decrease in the relative gene expression of the exopolysaccharides and quorum sensing encoding genes sheds the light on the mechanism of action of ginger and wild blueberry's constituents as well as polysorbates 20 and 80 on P. aeruginosa biofilm formation. Future studies need to assess the antibiofilm effect of each fraction of herbal extracts separately.