Exploring the synergistic effects of indole acetic acid (IAA) and compost in the phytostabilization of nickel (Ni) in cauliflower rhizosphere.

Heavy metals (HMs) contamination, owing to their potential links to various chronic diseases, poses a global threat to agriculture, environment, and human health. Nickel (Ni) is an essential element however, at higher concentration, it is highly phytotoxic, and affects major plant functions. Beneficial roles of plant growth regulators (PGRs) and organic amendments in mitigating the adverse impacts of HM on plant growth has gained the attention of scientific community worldwide. Here, we performed a greenhouse study to investigate the effect of indole-3-acetic acid (IAA @ 10- 5 M) and compost (1% w/w) individually and in combination in sustaining cauliflower growth and yield under Ni stress. In our results, combined application proved significantly better than individual applications in alleviating the adverse effects of Ni on cauliflower as it increased various plant attributes such as plant height (49%), root length (76%), curd height and diameter (68 and 134%), leaf area (75%), transpiration rate (36%), stomatal conductance (104%), water use efficiency (143%), flavonoid and phenolic contents (212 and 133%), soluble sugars and protein contents (202 and 199%), SPAD value (78%), chlorophyll 'a and b' (219 and 208%), carotenoid (335%), and NPK uptake (191, 79 and 92%) as compared to the control. Co-application of IAA and compost reduced Ni-induced electrolyte leakage (64%) and improved the antioxidant activities, including APX (55%), CAT (30%), SOD (43%), POD (55%), while reducing MDA and H2O2 contents (77 and 52%) compared to the control. The combined application also reduced Ni uptake in roots, shoots, and curd by 51, 78 and 72% respectively along with an increased relative production index (78%) as compared to the control. Hence, synergistic application of IAA and compost can mitigate Ni induced adverse impacts on cauliflower growth by immobilizing it in the soil.

Emicizumab Prophylaxis in Patients with Severe Hemophilia A: Insights from A Resource Limited Country.

METHODS: In this prospective study, severe HA patients were recruited from January 2022 to June 2023. Inhibitor positive and inhibitor negative patients with annual bleeding rate (ABR) 8 or greater and past histories of bleeding like intra-cranial, intra-abdominal, and pseudo-tumors were included. Emicizumab loading dose was 3 mg/kg in the first 4 weeks, and the maintenance dose was started at week 5 at 6 mg/kg/month. Patients' detailed bleeding history and demographics were recorded. The five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) was used to evaluate patients' HRQoL. Furthermore, Hemophilia Joint Health Score (HJHS) and Functional Independence score in Hemophilia (FISH) were applied for the assessment of joints at different time points. Results were analyzed by SPSS version 21. RESULTS: A total of 36 HA male patients with the mean age of 19.7 ± 14.42 years were recruited in the study; among them, 19 patients were inhibitor positive, while 17 were negative. Patients clinically presented with bleeding symptoms which included: hemarthrosis 95%, GI bleeding 13.8%, and bruises and gums bleeding 13.8%. Significant reduction was observed in the bleeding episodes after the therapeutic intervention, and joints assessment and Euro-Quality-of-life Visual Analog Scale showed a significant improvement in health after treatment. Similarly, there was a remarkable reduction in bleeding episodes and improved quality of life among HA patients. The ABR decreased from 53.6% episodes per year prior to treatment to 2.4% during Emicizumab therapy. Prior to initiating Emicizumab therapy, participants exhibited an average FISH score of 16 and HJHS score of 10, indicating moderate limitations due to joint-related issues. After treatment, the mean FISH score improved to 9 and HJHS score to 4 reflecting a substantial enhancement in participants' ability to perform daily activities (P < 0.057). CONCLUSION: Our results showed that HA patients on prophylactic treatment with Emicizumab were less restricted and had improved quality of life due to marked decrease in bleeding episodes which resulted in improved health and social lives. In addition, it was well tolerated, and no participant discontinued treatment because of adverse events.

Screening for orthostatic hypotension in the geriatric population in a real-world primary care setting reduces prescribed antihypertensive medications.

BACKGROUND: To determine if outpatient screening for orthostatic hypotension (OH) in the geriatric population results in fewer prescribed antihypertensive medications and if a relationship exists between OH and specific pharmacologic classes of antihypertensive medications. MATERIALS AND METHODS: Patients ≥ 65 years were screened for OH, defined as a decrease in systolic blood pressure (SBP) ≥ 20 mm Hg or a decrease in diastolic blood pressure (DBP) ≥ 10 mm Hg after standing for 3 minutes. Sitting blood pressure (BP) was measured after patients had been seated quietly in an exam room. Patients then stood for approximately 3 minutes at which time standing BP was recorded. RESULTS: OH prevalence was 18%. Standing DBP was significantly different between the two groups (70 mmHg ± 18, 80 mmHg ± 13, P  = 0.007). Compared to patients without OH, patients with OH were more likely to have been previously prescribed beta-blockers (56% vs. 32%, P  = 0.056) and potassium-sparing diuretics (11% vs. 1%, P  = 0.026). Physicians discontinued an antihypertensive medication more often in patients who screened positive for OH than in to those who did not (17% vs. 4%, P  = 0.037). Calcium channel blockers were the most frequently discontinued class of medication. CONCLUSION: Asymptomatic OH is prevalent in geriatric patients. Screening for OH may lead to de-escalation of antihypertensive regimen and a reduction in polypharmacy. Positive screening for OH was associated with de-prescribing of antihypertensive medications. Prior use of beta-blockers and potassium-sparing diuretics was most largely associated with OH.

Mycophenolate Mofetil-Induced Colonic Injury Manifesting Endoscopically As Ischemic Colitis.

Mycophenolate mofetil (MMOF) is a commonly used immunosuppressive prodrug in kidney transplant patients. However, it is not without side effects. The most common of these is diarrhea which inadvertently leads to colonoscopic and endoscopic evaluation when all other workup returns negative. Colonoscopies often show diffuse ulcers and colitis changes depending on the degree of diarrhea. In rare situations, MMOF-induced ischemic colitis may occur on gross endoscopy. We describe an unusual phenomenon of an adult male status post renal transplant with histopathologically diagnosed MMOF-induced colitis who developed gross endoscopic findings concerning ischemic colitis. Our case highlights the importance of recognizing that MMOF-induced colonic changes can rarely mimic ischemic colitis. With this in mind, we aim for gastroenterologists to better understand the varying endoscopic colonic findings of this immunosuppressive drug.

Cigarette Smoke and Nicotine-Containing Electronic-Cigarette Vapor Downregulate Lung WWOX Expression, Which Is Associated with Increased Severity of Murine Acute Respiratory Distress Syndrome.

A history of chronic cigarette smoking is known to increase risk for acute respiratory distress syndrome (ARDS), but the corresponding risks associated with chronic e-cigarette use are largely unknown. The chromosomal fragile site gene, WWOX, is highly susceptible to genotoxic stress from environmental exposures and thus an interesting candidate gene for the study of exposure-related lung disease. Lungs harvested from current versus former/never-smokers exhibited a 47% decrease in WWOX mRNA levels. Exposure to nicotine-containing e-cigarette vapor resulted in an average 57% decrease in WWOX mRNA levels relative to vehicle-treated controls. In separate studies, endothelial (EC)-specific WWOX knockout (KO) versus WWOX flox control mice were examined under ARDS-producing conditions. EC WWOX KO mice exhibited significantly greater levels of vascular leak and histologic lung injury. ECs were isolated from digested lungs of untreated EC WWOX KO mice using sorting by flow cytometry for CD31+ CD45-cells. These were grown in culture, confirmed to be WWOX deficient by RT-PCR and Western blotting, and analyzed by electric cell impedance sensing as well as an FITC dextran transwell assay for their barrier properties during methicillin-resistant Staphylococcus aureus or LPS exposure. WWOX KO ECs demonstrated significantly greater declines in barrier function relative to cells from WWOX flox controls during either methicillin-resistant S. aureus or LPS treatment as measured by both electric cell impedance sensing and the transwell assay. The increased risk for ARDS observed in chronic smokers may be mechanistically linked, at least in part, to lung WWOX downregulation, and this phenomenon may also manifest in the near future in chronic users of e-cigarettes.

Feasibility of Repurposing Clioquinol for Cancer Therapy.

BACKGROUND: Cancer is a prevalent disease in the world and is becoming more widespread as time goes on. Advanced and more effective chemotherapeutics need to be developed for the treatment of cancer to keep up with this prevalence. Repurposing drugs is an alternative to discover new chemotherapeutics. Clioquinol is currently being studied for reposition as an anti-cancer drug. OBJECTIVE: This study aimed to summarize the anti-cancer effects of clioquinol and its derivatives through a detailed literature and patent review and to review their potential re-uses in cancer treatment. METHODS: Research articles were collected through a PubMed database search using the keywords "Clioquinol" and "Cancer." The keywords "Clioquinol Derivatives" and "Clioquinol Analogues" were also used on a PubMed database search to gather research articles on clioquinol derivatives. Patents were gathered through a Google Patents database search using the keywords "Clioquinol" and "Cancer." RESULTS: Clioquinol acts as a copper and zinc ionophore, a proteasome inhibitor, an anti-angiogenesis agent, and is an inhibitor of key signal transduction pathways responsible for its growth-inhibitory activity and cytotoxicity in cancer cells preclinically. A clinical trial conducted by Schimmer et al., resulted in poor outcomes that prompted studies on alternative clioquinol-based applications, such as new combinations, new delivery methods, or new clioquinol-derived analogues. In addition, numerous patents claim alternative uses of clioquinol for cancer therapy. CONCLUSION: Clioquinol exhibits anti-cancer activities in many cancer types, preclinically. Low therapeutic efficacy in a clinical trial has prompted new studies that aim to discover more effective clioquinol- based cancer therapies.

Repurposing Disulfiram as An Anti-Cancer Agent: Updated Review on Literature and Patents.

BACKGROUND: Despite years of success of most anti-cancer drugs, one of the major clinical problems is inherent and acquired resistance to these drugs. Overcoming the drug resistance or developing new drugs would offer promising strategies in cancer treatment. Disulfiram, a drug currently used in the treatment of chronic alcoholism, has been found to have anti-cancer activity. OBJECTIVE: To summarize the anti-cancer effects of Disulfiram through a thorough patent review. METHODS: This article reviews molecular mechanisms and recent patents of Disulfiram in cancer therapy. RESULTS: Several anti-cancer mechanisms of Disulfiram have been proposed, including triggering oxidative stress by the generation of reactive oxygen species, inhibition of the superoxide dismutase activity, suppression of the ubiquitin-proteasome system, and activation of the mitogen-activated protein kinase pathway. In addition, Disulfiram can reverse the resistance to chemotherapeutic drugs by inhibiting the P-glycoprotein multidrug efflux pump and suppressing the activation of NF-kB, both of which play an important role in the development of drug resistance. Furthermore, Disulfiram has been found to reduce angiogenesis because of its metal chelating properties as well as its ability to inactivate Cu/Zn superoxide dismutase and matrix metalloproteinases. Disulfiram has also been shown to inhibit the proteasomes, DNA topoisomerases, DNA methyltransferase, glutathione S-transferase P1, and O6- methylguanine DNA methyltransferase, a DNA repair protein highly expressed in brain tumors. The patents described in this review demonstrate that Disulfiram is useful as an anti-cancer drug. CONCLUSION: For years the FDA-approved, well-tolerated, inexpensive, orally-administered drug Disulfiram was used in the treatment of chronic alcoholism, but it has recently demonstrated anti-cancer effects in a range of solid and hematological malignancies. Its combination with copper at clinically relevant concentrations might overcome the resistance of many anti-cancer drugs in vitro, in vivo, and in patients.

Acute Hepatitis in Infections Caused by Dengue Virus in Southern Punjab, Pakistan.

Background Dengue is the most common vector-borne disease worldwide. It poses a significant health burden in tropical and subtropical countries. Common clinical presentations include retro-orbital pain, fever, headache, nausea, vomiting and aches and pains in the body. A severe form of dengue fever is known as dengue hemorrhagic fever (DHF) that includes signs of hemorrhage. Besides the typical signs and symptoms, atypical presentations of dengue include myositis, hepatitis and encephalitis. Hepatic involvement in dengue has varied presentations. This study aims to highlight the importance of acute hepatitis, an atypical presentation in dengue patients. Methods  We conducted a descriptive, cross-sectional study in the Medical Unit-1 of Bahawal Victoria Hospital, Bahawalpur, a tertiary-care hospital serving the area of Southern Punjab, Pakistan. The relevant medical records of 63 patients admitted with dengue-associated hepatitis to the Medical Unit-1 of Bahawal Victoria Hospital, Bahawalpur, between January 1, 2015 and December 1, 2016, were reviewed. Informed consent was given. Information regarding demographic variables and disease course was collected and analyzed. Results  This study included 55 men (87.3%) and eight (12.7%) women. Fifty (79.3%) patients were diagnosed with dengue fever (DF). Thirteen patients were managed on the lines of DHF. Out of the total 63 patients, only six were locals. The common clinical presentations in these patients included high fever, retro-orbital pain, severe headache, rash, dark-colored urine, bleeding problems and hepatomegaly. Higher levels of aspartate aminotransferase (AST) were noted in comparison to alanine transferase (ALT). Despite the complicated clinical course in some patients, all patients were managed successfully and discharged, except one. Conclusion The frequency of acute hepatitis in dengue patients is high, especially in young men. Early diagnosis and prompt treatment are necessary for better prognosis. Although no specific treatment guidelines are available, supportive treatment in a timely fashion can prevent complications. Transfusion with packed cell volume (PCV) and N-acetyl cysteine (NAC) has produced promising results.

Pulmonary nocardiosis in an adolescent patient with Crohn's disease treated with infliximab: a serious complication of TNF-alpha blockers.

Nocardiosis is a serious complication of tumor necrosis factor (TNF) alpha blockers. With the increasing use of biologics for inflammatory bowel disease, it is to be anticipated that opportunistic infections such as nocardia will be more frequently encountered in children. We present the case of a 16 year old male with Crohn's disease who developed pulmonary nocardiosis during the course of his treatment with infliximab. This case illustrates the diagnostic and therapeutic challenges faced in patients with inflammatory bowel disease infected with opportunistic organisms. Pediatric health care providers need to be aware so that early diagnosis and treatment can be provided thereby preventing disseminated disease and having favorable outcomes. Although TNF blocker therapy must be discontinued in the presence of such infections, biologic therapy may be reintroduced after successful treatment with trimethoprim-sulfamethoxazole to control underlying symptoms of inflammatory bowel disease.

Cytomegaloviral enteritis: a rare cause of small gut perforation.

A 47-year-old man was admitted with four months history of pain upper central abdomen associated with passage of 3-4 loose watery stools per day. Abdominal examination revealed soft abdomen with mild tenderness in the para-umbilical region. There was associated hepatomegaly. His Hb% was low, liver and renal functions were deranged. Upper GI endoscopy revealed antral ulcer, and colonoscopy revealed a caecal ulcer, which were biopsied. Liver biopsy was also done. Histopathology report showed evidence of inflammatory colitis and chronic hepatitis, so a diagnosis of inflammatory bowel disease with autoimmune hepatitis was made. He was negative for HIV and hepatitis serology. He was given long list of medicine including steroids but the symptoms did not improve. Two months after admission he developed severe abdominal pain associated with distension. The X-Ray chest revealed pneumoperitoneum and laparotomy was carried out which revealed a small perforation in terminal ileum associated with multiple circular indurated areas ranging from few mm to 1.5 Cm in size with central thinning spread over distal half of small gut and enlarged mesenteric lymph nodes. The biopsy of perforated area revealed cytomegaloviral enteritis. Postoperatively patient developed ARDS and died on 13th postoperative day.

Gastrointestinal norovirus infection associated with exacerbation of inflammatory bowel disease.

OBJECTIVE: In this study we aimed to determine, in pediatric patients, whether norovirus infection could be associated with exacerbations of inflammatory bowel disease (IBD) and ascertain whether the clinical expression of norovirus gastroenteritis was similar in patients with IBD compared with non-IBD controls. MATERIALS AND METHODS: We performed a case-control retrospective chart review, over a 10-month interval, of patients with IBD with an exacerbation of their disease. The presence of norovirus in stool and/or rectal swab samples, as determined by an enzyme-linked immunoassay, was assessed. In addition, sex, age, type of IBD, presence or absence of diarrhea, hematochezia, and the need for hospitalization were determined. A similar number of control patients who did not have IBD were used as controls. RESULTS: Nine patients with IBD (8 ulcerative colitis/1 Crohn disease) had exacerbations with diarrhea. Eight had norovirus antigen in at least 1 sample. All 9 patients with IBD presented with bloody diarrhea and 6 of the 8 norovirus-positive patients with IBD required hospitalization. All of the control patients experienced diarrhea; however, no hematochezia was noted and no hospitalization was required. Several patients with IBD and controls remained positive for norovirus months after the initial positive stool and/or rectal swab sample. The virus appeared to be more common during winter months. CONCLUSIONS: We conclude that norovirus may be associated with exacerbations of IBD. When norovirus accompanies IBD it is more likely to be associated with hematochezia than when the infection occurs in the absence of IBD.