Molecular Simulation Studies of Pharmaceutical Pollutant Removal (Rosuvastatin and Simvastatin) Using Novel Modified-MOF Nanostructures (UIO-66, UIO-66/Chitosan, and UIO-66/Oxidized Chitosan).

The ubiquitous presence of pharmaceutical pollutants in the environment significantly threatens human health and aquatic ecosystems. Conventional wastewater treatment processes often fall short of effectively removing these emerging contaminants. Therefore, the development of high-performance adsorbents is crucial for environmental remediation. This research utilizes molecular simulation to explore the potential of novel modified metal-organic frameworks (MOFs) in pharmaceutical pollutant removal, paving the way for the design of efficient wastewater treatment strategies. Utilizing UIO-66, a robust MOF, as the base material, we developed UIO-66 functionalized with chitosan (CHI) and oxidized chitosan (OCHI). These modified MOFs' physical and chemical properties were first investigated through various characterization techniques. Subsequently, molecular dynamics simulation (MDS) and Monte Carlo simulation (MCS) were employed to elucidate the adsorption mechanisms of rosuvastatin (ROSU) and simvastatin (SIMV), two prevalent pharmaceutical pollutants, onto these nanostructures. MCS calculations demonstrated a significant enhancement in the adsorption energy by incorporating CHI and OCHI into UIO-66. This increased ROSU from -14,522 to -16,459 kcal/mol and SIMV from -17,652 to -21,207 kcal/mol. Moreover, MDS reveals ROSU rejection rates in neat UIO-66 to be at 40%, rising to 60 and 70% with CHI and OCHI. Accumulation rates increase from 4 Å in UIO-66 to 6 and 9 Å in UIO-CHI and UIO-OCHI. Concentration analysis shows SIMV rejection surges from 50 to 90%, with accumulation rates increasing from 6 to 11 Å with CHI and OCHI in UIO-66. Functionalizing UIO-66 with CHI and OCHI significantly enhanced the adsorption capacity and selectivity for ROSU and SIMV. Abundant hydroxyl and amino groups facilitated strong interactions, improving performance over that of unmodified UIO-66. Surface functionalization plays a vital role in customizing the MOFs for pharmaceutical pollutant removal. These insights guide next-gen adsorbent development, offering high efficiency and selectivity for wastewater treatment.

Ogilvie's Syndrome in a Young Female With Chronic Constipation.

Ogilvie's syndrome, also known as acute colonic pseudo-obstruction, is often encountered in post-surgical patients or those with serious comorbidities requiring intensive care. For this reason, it has rarely been reported in patients younger than 50 years without any predisposing risk factors. Our case report highlights a unique case of Ogilvie's syndrome in a young female with no recent trauma or surgical history. To that extent, we discuss risk factors that predisposed her to this condition, including her history of chronic constipation. We also emphasize the need for outpatient workups for such patients to prevent the worsening of their symptoms.

A Challenging Case of Metastatic Non-Small Cell Carcinoma of the Lung.

Primary lung carcinoma with distant metastasis is a life-threatening diagnosis that presents many unique challenges due to the severity of the disease at the time of presentation. We investigated a life-threatening primary lung carcinoma with distant metastasis in a 73-year-old transgender woman, which posed unique challenges due to the advanced stage of the disease at presentation. The patient exhibited nonspecific musculoskeletal and neurological symptoms resulting from the primary lung carcinoma metastasizing to her liver, bones, and brain. We evaluated various imaging modalities that aided in determining the disease's severity and identifying complications related to metastasis. Although these efforts can offer symptomatic relief, the overall prognosis remains poor when metastasis spreads to multiple organs, particularly the brain, as remission may no longer be attainable.

Antimicrobial resistance among clinical Vibrio cholerae non-O1/non-O139 isolates: systematic review and meta-analysis.

Non-O1/non-O139 Vibrio cholerae (NOVC) are nonpathogenic or asymptomatic colonizers in humans, but they may be related to intestinal or extra-intestinal (severe wound infections or sepsis) infections in immunocompromised patients.The present study aimed to evaluate the weighted pooled resistance (WPR) rates in clinical NOVC isolates based on different years, areas, quality, antimicrobial susceptibility testing (AST), and resistance rates. We systematically searched the articles in PubMed, Scopus, and Embase (until January 2020). Data analyses were performed using the Stata software program (version 17). A total of 16 studies that had investigated 824 clinical NOVC isolates were included in the meta-analysis. The majority of the studies were conducted in Asia (n = 14) and followed by Africa (n = 2). The WPR rates were as follows: erythromycin 10%, ciprofloxacin 5%, cotrimoxazole 27%, and tetracycline 13%. There was an increase in resistance to ciprofloxacin, nalidixic acid, and gentamicin, norfloxacin during the period from 2000 to 2020. On the contrary, there was a decreased resistance to erythromycin, tetracycline, chloramphenicol, cotrimoxazole, ampicillin, streptomycin, kanamycin, and neomycin during the period from 2000 to 2020. The lowest resistance rate were related to gentamicin, kanamycin, ciprofloxacin, and chloramphenicol against NOVC strains. However, temporal changes in antimicrobial resistance rate were found in our study. We established continuous surveillance, careful appropriate AST, and limitations on improper antibiotic usage, which are essential, especially in low-income countries.

Occupational risk assessment of organophosphates with an emphasis on psychological and oxidative stress factors.

Organophosphate pesticides (OPPs) are widely used all over the world in domestic and industrial settings, but these chemicals affect the nervous system, induce suicidal thoughts, depression and anxiety, and impair sleep quality. The purpose of this study was to investigate the relationship between the main toxicity mechanisms of OPPs, oxidative stress and cholinesterase inhibition, and psychological parameters in chronic exposure to OPPs. This cross-sectional study was conducted on 56 male OPPs factory workers as the worker group and 47 unexposed individuals within the same age range as the control group. Psychological factors were assessed using validated questionnaires. The activity of plasma cholinesterase and oxidative stress biomarkers, total antioxidant capacity of plasma, lipid peroxidation (LPO), and protein carbonylation were determined in blood samples by spectrophotometer. Sleep quality score in the factory workers was lower, and depression and suicidal ideation scores were higher than those in the control group. These factory workers showed 35% lower levels of plasma cholinesterase activity than did the controls. Compared to the control group, a significant impairment in oxidative stress biomarkers was also observed in the workers. Meanwhile, there was a significant relationship between the duration of employment and the level of LPO as well as a significant correlation between the quality of sleep and plasma cholinesterase in the workers. In conclusion, long-term exposure to OPPs could cause oxidative damages and neurobehavioral effects. The close monitoring of workplace exposure to organophosphates pesticides and also their respective solvents along with the reduction of working hours are of the necessities to avoid the adverse impacts of exposure to these pesticides.

Global status of antimicrobial resistance among environmental isolates of Vibrio cholerae O1/O139: a systematic review and meta-analysis.

BACKGROUND: Vibrio cholerae O1/O139 were the predominant circulating serogroups exhibiting multi-drug resistance (MDR) during the cholera outbreak which led to cholera treatment failures. OBJECTIVE: This meta-analysis aimed to evaluate the weighted pooled resistance (WPR) rates in V. cholerae O1/O139 isolates obtained from environmental samples. METHODS: We systematically searched the articles in PubMed, Scopus, and Embase (until January 2020). Subgroup analyses were then employed by publication year, geographic areas, and the quality of studies. Statistical analyses were conducted using STATA software (ver. 14.0). RESULTS: A total of 20 studies investigating 648 environmental V. cholerae O1/O139 isolates were analysed. The majority of the studies were originated from Asia (n = 9). In addition, a large number of studies (n = 15 i.e. 71.4%) included in the meta-analysis revealed the resistance to cotrimoxazole and ciprofloxacin. The WPR rates were as follows: cotrimoxazole 59%, erythromycin 28%, tetracycline 14%, doxycycline 5%, and ciprofloxacin 0%. There was increased resistance to nalidixic acid, cotrimoxazole, furazolidone, and tetracycline while a decreased resistance to amoxicillin, ciprofloxacin, erythromycin, chloramphenicol, ampicillin, streptomycin, and ceftriaxone was observed during the years 2000-2020. A significant decrease in the doxycycline and ciprofloxacin-resistance rates in V. cholerae O1/O139 isolates was reported over the years 2011-2020 which represents a decrease in 2001-2010 (p < 0.05). CONCLUSIONS: Fluoroquinolones, gentamicin, ceftriaxone, doxycycline, kanamycin, and cefotaxime showed the highest effectiveness and the lowest resistance rate. However, the main interest is the rise of antimicrobial resistance in V. cholerae strains especially in low-income countries or endemic areas, and therefore, continuous surveillance, careful appropriate AST, and limitation on improper antibiotic usage are crucial.

Breast Tumor Targeting with PAMAM-PEG-5FU-99mTc As a New Therapeutic Nanocomplex: In In-vitro and In-vivo studies.

Dendrimer-based targeted drug delivery, as an innovative polymeric drug-delivery system, is promising for cancer therapy. Folate receptors (FR) are overexpressed in many types of tumor cells, such as breast cell carcinomas, which allow folate-targeted delivery. Therefor polyethylene glycol (PEG) modified-PAMAM G4 dendrimers were functionalized with folic acid (FA), as targeting agent. Then, 5-FU (5-fluorouracil) and 99mTc (technetium-99 m) as therapeutic agents were respectively loaded and conjugated to previous nano-complex (PEG-PAMAM G4-FA-5FU-99mTc). The value of drug loading was calculated by TGA analysis (16.97%). Drug release profiles of PEG-PAMAM G4-FA-5FU-99mTc and PEG-PAMAM G4-FA-5FU were evaluated. The radiochemical purity of PEG-PAMAM G4-FA-5FU-99mTc and PEG-PAMAM G4-FA-99mTc was obtained at >95% with excellent in-vitro and in-vivo stabilities. PEG-PAMAM G4-FA-5FU-99mTc was synthesized and the stability studies were carried out by the ITLC methods in serum (86.67% and 83.75%) and PBS. Combinational therapy effects of 5-FU and 99mTc containing nano-complexes were evaluated on 4 T1 (mouse breast cancer) and MDA-MB-231 (human breast adenocarcinoma) cancer cell lines. Excellent uptake values were obtained for FA-decorated nano-complexes on 4 T1 and MDA-MB-231 cell lines. Subsequently, tumor inhibition effects of PEG-PAMAM G4-FA-5FU-99mTc and PEG-PAMAM G4-FA-5FU were evaluated using the breast tumor-bearing BALB/C mice. Graphical abstract Breast Tumor Targeting with PAMAM-PEG-5FU- 99mTc As a New Therapeutic Nanocomplex: in In-vitro and In-vivo Studies was presented. This targeted drug delivery system can significantly increase the efficiency of cancer therapy, and reduce the treatment cost and time.

A Rare Case of Non-Small Cell Lung Cancer with BRAF V600E Gene: Case Report and Literature Review.

Non-small cell lung cancer is one of the leading causes of mortality in the United States. The BRAF mutation, which has been associated with malignant melanoma, has been documented in only 3.5-5% of the non-small cell lung cancer (NSCLC) patient population.The involvement of the BRAF mutation in NSCLC and the treatment for tumors with such mutations is still an evolving topic of interest, which is why more in depth information is warranted. We present a rare case of stage IV non-small cell lung adenocarcinoma, who presented first with a complicated pericardial effusion with evidence of malignant effusion. He had genetic testing done, revealing he had a positive BRAF V600E mutation. He was put on multiple chemotherapy regimens, but was most responsive to Vemurafenib. This case will shed light into the importance of the BRAF V600E gene and its importance in NSCLC for better prognosis value.

Complete Eye Ophthalmoplegia: the unusual initial presentation of Leptomeningeal Carcinomatosis.

Ophthalmoplegia is a paralysis or weakness of extraocular muscles that have a variety of different etiologies including and not limited to Leptomeningeal Carcinomatosis (LC). LC is caused mainly by metastatic cancers and can cause a wide variety of symptoms. We present a case of LC with no preexisting condition who presented with a unilateral ophthalmoplegia as initial presentation who was found to have LC secondary to large B-cell lymphoma.

Pulmonary arterial hypertension: A rare yet fatal complication of Neurofibromatosis Type 1.

Neurofibromatosis Type 1 (NF1) is an autosomal dominant genetic disorder with an incidence of approximately 1 in 4,000 live births [1]. Pulmonary arterial hypertension (PAH) is a rare but extremely life-threatening complication associated with NF1. Timely recognition of this unusual and severe association between NF1 and PAH is imperative in prolonging the survival in this specific patient population. We present the clinical outcomes of a 47-year old female previously diagnosed with NF1, who presented with progressively worsening dyspnea.

Novel chlorambucil-conjugated anionic linear-globular PEG-based second-generation dendrimer: in vitro/in vivo improved anticancer activity.

Evaluating the efficacy of anticancer drugs is an evolving and research-oriented issue. The objective of this study was to reduce the insolubility of chlorambucil (CBL) in water and improve the anticancer activity of CBL in vitro and in vivo through the conjugation of CBL with anionic linear-globular dendrimer (second generation, G2). In the current study, the anticancer activity among three groups that include CBL, CBL-G2 dendrimer, and control was measured in vitro and in vivo. In vitro studies showed that G2 anionic linear-globular polyethylene-glycol-based dendrimer, which conjugated to the CBL exterior through an ester linkage, was able to significantly improve the treatment efficacy over clinical CBL alone with respect to proliferation assay, 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide; half maximal inhibitory concentration (IC50) was calculated to be 141 µg/mL for CBL alone and 27.7 µg/mL for CBL-G2 dendrimer; P<0.05. In addition, CBL-G2 dendrimer conjugate forestalled the growth of MCF-7 cancerous cells in addition to enhancing the number of apoptotic and necrotic cells as demonstrated by an annexin V-fluorescein isothiocyanate assay. CBL-G2 dendrimer conjugate was able to checkmate antiapoptotic Bcl-2 expression and Bcl-2/Bax ratio in a large scale compared with the control group and CBL alone (P<0.005). In vivo studies showed that tumor treatment by CBL-G2 dendrimer conjugate outstrips the efficacy of treatment compared with CBL alone. The evaluation was based on reduction in tumor volume and tumor growth inhibition of murine 4T1 mammary tumor cells. Tumor volume of 140%±8% was measured in the treatment with CBL-G2 dendrimer, whereas 152%±13.5% was calculated in the treatment with free CBL (P<0.05). However, there were no significant differences in histological assay among the three groups. In conclusion, tumor growth suppression potential of CBL-G2 dendrimer, which was assessed in both in vitro and in vivo experiments, has provided empirical evidence to buttress the fact that this compound could be considered for functional cancer treatment with low side effects.

Effect of estrogen and/or progesterone administration on traumatic brain injury-caused brain edema: the changes of aquaporin-4 and interleukin-6

The role of aquaporin-4 (AQP4) and interleukin-6 (IL-6) in the development of brain edema post-traumatic brain injury (TBI) has been indicated. The present study was designed to investigate the effect(s) of administration of progesterone (P) and/or estrogen (E) on brain water content, AQP4 expression, and IL-6 levels post-TBI. The ovariectomized rats were divided into 11 groups: sham, one vehicle, two vehicles, E1, E2, P1, P2, E1 + P1, E1 + P2, E2 + P1, and E2 + P2. The brain AQP4 expression, IL-6 levels, and water content were evaluated 24 h after TBI induced by Marmarou’s method. The low (E1 and P1) and high (E2 and P2) doses of estrogen and progesterone were administered 30 min post-TBI. The results showed that brain water content and AQP4 expression decreased in the E1, E2, P1, and P2-treated groups. The administration of E1 decreased IL-6 levels. Addition of progesterone decreased the inhibitory effect of E1 and E2 on the accumulation of water in the brain. Administration of E1 + P1 and E1 + P2 decreased the inhibitory effect of E1 on the IL-6 levels and AQP4 protein expression. Our findings suggest that estrogen or progesterone by itself has more effective roles in decrease of brain edema than combination of both. Possible mechanism may be mediated by the alteration of AQP4 and IL-6 expression. However, further studies are required to verify the exact mechanism (AU)

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Effect of estrogen and/or progesterone administration on traumatic brain injury-caused brain edema: the changes of aquaporin-4 and interleukin-6.

The role of aquaporin-4 (AQP4) and interleukin-6 (IL-6) in the development of brain edema post-traumatic brain injury (TBI) has been indicated. The present study was designed to investigate the effect(s) of administration of progesterone (P) and/or estrogen (E) on brain water content, AQP4 expression, and IL-6 levels post-TBI. The ovariectomized rats were divided into 11 groups: sham, one vehicle, two vehicles, E1, E2, P1, P2, E1 + P1, E1 + P2, E2 + P1, and E2 + P2. The brain AQP4 expression, IL-6 levels, and water content were evaluated 24 h after TBI induced by Marmarou's method. The low (E1 and P1) and high (E2 and P2) doses of estrogen and progesterone were administered 30 min post-TBI. The results showed that brain water content and AQP4 expression decreased in the E1, E2, P1, and P2-treated groups. The administration of E1 decreased IL-6 levels. Addition of progesterone decreased the inhibitory effect of E1 and E2 on the accumulation of water in the brain. Administration of E1 + P1 and E1 + P2 decreased the inhibitory effect of E1 on the IL-6 levels and AQP4 protein expression. Our findings suggest that estrogen or progesterone by itself has more effective roles in decrease of brain edema than combination of both. Possible mechanism may be mediated by the alteration of AQP4 and IL-6 expression. However, further studies are required to verify the exact mechanism.

Investigation of the effect of nanoclay on the properties of quince seed mucilage edible films.

Some physical properties like Gas barrier, thermal stability, and mechanical properties and brittleness of pure biopolymers film are inadequate for food packaging. The functional properties of quince seed mucilage-based films were enhanced by addition of nanoclay (NC) (Cloisite 30B). Edible films were cast from heated aqueous solutions of quince seed (10% w/w) and NC (0.5%, 1%, 1.5%, and 2% w/w of quince seed). The effect of NC was studied in terms of tensile properties, water vapor permeability (WVP), oxygen permeability, and glass transition temperature (T g) of the nano composite films. In films containing NC, ultimate tensile strength enhanced to 22 MPa, and elongation increased from 2.48% to 6.5%. The addition of NC also improved gas barrier properties of the films. In films containing 2% NC, WVP decreased from 6.69 × 10(-7) g·m(-1)·h(-1)·Pa(-1) to 1.10 × 10(-7) g·m(-1)·h(-1)·Pa(-1) and oxygen permeability declined to 13.68 mL·day·m-(2). NC also influences glass transition temperature significantly. The study demonstrated that the properties of quince seed mucilage edible films can be significantly improved using NC as reinforcement.