Reduction of 4-nitrophenol using green-fabricated metal nanoparticles

Noble metal (silver (Ag), gold (Au), platinum (Pt), and palladium (Pd)) nanoparticles have gained increasing attention due to their importance in several research fields such as environmental and medical research. This review focuses on the basic perceptions of the green synthesis of metal nanoparticles and their supported-catalyst-based reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP). The mechanisms for the formation of these nanoparticles and the catalytic reduction of 4-NP are discussed. Furthermore, the parameters that need to be considered in the catalytic efficiency calculations and perspectives for future studies are also discussed.

Noble metal (silver (Ag), gold (Au), platinum (Pt), and palladium (Pd)) nanoparticles have gained increasing attention due to their importance in several research fields such as environmental and medical research.     

Exploration and insights into the cellular internalization and intracellular fate of amphiphilic polymeric nanocarriers

The beneficial or deleterious effects of nanomedicines emerge from their complex interactions with intracellular pathways and their subcellular fate. Moreover, the dynamic nature of plasma membrane accounts for the movement of these nanocarriers within the cell towards different organelles thereby not only influencing their pharmacokinetic and pharmacodynamic properties but also bioavailability, therapeutic efficacy and toxicity. Therefore, an in-depth understanding of underlying parameters controlling nanocarrier endocytosis and intracellular fate is essential. In order to direct nanoparticles towards specific sub-cellular organelles the physicochemical attributes of nanocarriers can be manipulated. These include particle size, shape and surface charge/chemistry. Restricting the particle size of nanocarriers below 200 nm contributes to internalization via clathrin and caveolae mediated pathways. Similarly, a moderate negative surface potential confers endolysosomal escape and targeting towards mitochondria, endoplasmic reticulum (ER) and Golgi. This review aims to provide an insight into these physicochemical attributes of nanocarriers fabricated using amphiphilic graft copolymers affecting cellular internalization. Fundamental principles understood from experimental studies have been extrapolated to draw a general conclusion for the designing of optimized nanoparticulate drug delivery systems and enhanced intracellular uptake via specific endocytic pathway.KEY WORDS: Amphiphilic, Copolymer, Nanoparticles, Internalization, Intracellular fate     

Shoulder magnetic resonance imaging findings in manual wheelchair users with spinal cord injury

Objective: To investigate the prevalence of rotator cuff and long head of the biceps pathologies in manual wheelchair (MWC) users with spinal cord injury (SCI).Design: Cross-sectional study.Setting: Outpatient clinic at a tertiary medical center.Participants: Forty-four adult MWC users with SCI (36 men and 8 women) with an average age (SD) of 42 (13) years. SCI levels ranged from C6 to L1; complete and incomplete SCI.Outcome Measures: Participants’ demographic and anthropometric information, presence of shoulder pain, Wheelchair User’s Pain Index (WUSPI) scores, and magnetic resonance imaging findings of shoulder pathologies including tendinopathy, tendon tears, and muscle atrophy.Results: Fifty-nine percent of the participants reported some shoulder pain. The prevalence of any tendinopathy across the rotator cuff and the long head of biceps tendon was 98%. The prevalence of tendinopathy in the supraspinatus was 86%, infraspinatus was 91%, subscapularis was 75%, and biceps was 57%. The majority of tendinopathies had mild or moderate severity. The prevalence of any tears was 68%. The prevalence of tendon tears in the supraspinatus was 48%, infraspinatus was 36%, subscapularis was 43%, and biceps was 12%. The majority of the tears were partial-thickness tears. Participants without tendon tears were significantly younger (P < 0.001) and had been wheelchair user for a significantly shorter time (P = 0.005) than those with tendon tears.Conclusion: Mild and moderate shoulder tendinopathy and partial-thickness tendon tears were highly prevalent in MWC users with SCI. Additionally, the findings of this study suggest that strategies for monitoring shoulder pathologies in this population should not be overly reliant on patient-reported pain, but perhaps more concerned with years of wheelchair use and age.     

Additional mechanisms of hiatal hernia recurrence and its prevention

Summary The conventional hiatal hernia repair is a tension repair. Large defects such as those associated with an intrathoracic stomach can have a high rate of recurrence resulting in esophageal symptoms and in some instances gastric strangulation. Numerous additive procedures are used to secure the stomach in the abdominal cavity including mesh buttressing, fundoplication, anterior abdominal wall gastropexy and fundus diaphragmatic suture fixation. The optimal repair is unknown primarily because crura closure failure is poorly understood. A literature review was used to determine the proven causes of hiatal hernia recurrence. Early postoperative vomiting, surgeon inexperience, short esophagus and no crus closure are documented causes. In a series of 19 hiatal hernia recurrence repairs from our institution, additional causes such as suture pull-out and trauma have been established as additional mechanisms of recurrence. Increased intra-abdominal pressure associated with motor vehicle accidents was the precipitating factor in 2/19 patients. Suggested methods for prevention of hiatal disruption and resultant hernia are proposed which include: a postoperative antiemetic regimen, restricted activity in the early postoperative period, an assessment technique for the short esophagus when utilizing a laparoscopic approach, crus closure calibration and inclusion of the diaphragmatic fascia when performing hiatal closure for large paraesophageal hernias and the short esophagus.     

Association of genetic polymorphism of glutathione S-transferase M1, T1, P1 and susceptibility to bladder cancer

OBJECTIVE: Glutathione-S-transferases (GSTs) are active in the detoxification of wide variety of endogenous or exogenous carcinogens. We examined the association of the GST gene polymorphism with sporadic bladder cancer patients in Northern India. MATERIAL AND METHODS: The study constituted of 106 bladder cancer cases and 370 age-matched controls. The GSTT1 and GSTM1 null genotypes were identified by multiplex PCR and GSTP1313 A/G by Polymerase Chain Reaction/Restriction Fragment Length Polymorphism method (PCR/RFLP). RESULTS: We observed non-significant association in null alleles of the GSTM1 (p = 0.611, OR = 1.12, 95% CI = 0.72-1.74 and GSTT1 (p = 0.135, OR = 1.45, 95% CI = 0.89-2.37) with risk of bladder cancer. However, the G/G genotype of the GSTP1 gene polymorphism was highly significant when compared to controls (p=0.000, OR = 7.12, 95% CI = 3.14-16.16). The combined analysis of the three risk genotypes demonstrated further increase in the risk of bladder cancer (p = 0.000, OR = 7.29 95% CI = 2.81-18.93). CONCLUSION: Our study demonstrated that GSTP1313 G/G polymorphism is a strong predisposing risk factor for bladder cancer. Combination of three GST genotypes association exhibiting gene-gene interaction further substantiates the increased risk of bladder cancer.     

Clinical and pathologic features correlated with rare favorable survival in patients with BRAFV600E mutated colorectal cancer

BackgroundBRAF^V600E mutations occur in fewer than 10% of all patients with metastatic colorectal cancer (CRC) and arise from sessile serrated adenomas. Despite efficacy with targeted therapies against MAPK signaling and with immunotherapies in this population, survival outcomes for patients with BRAF^V600E mutated metastatic CRC in general are poor. Characteristics distinguishing patients with BRAF^V600E mutated metastatic CRC with favorable versus unfavorable outcomes have not been well annotated.MethodsRecords of 187 patients with BRAF^V600E mutated metastatic CRC evaluated at MD Anderson Cancer Center between 2005–2020 were reviewed. Patients with the shortest and longest metastatic survival (N=25 for each group) were compared. Associations between prognostic group and clinical/pathologic features were measured by odds ratio and for median survival by log-rank testing.ResultsMedian metastatic survival differed between the 2 BRAF^V600E mutated metastatic CRC populations (8.6 vs. 83.9 months, hazard ratio 32; P<0.0001). Patients with poor survival more commonly had hepatic involvement [75% vs. 28%, odds ratio (OR) 8.1, 95% confidence interval (CI): 2.3–29; P=0.001]. Patients with favorable survival were more likely to develop metachronous metastases (52% vs. 16%, OR 5.7, 95% CI: 1.5–21; P=0.01) and undergo definitive locoregional therapy to metastatic disease (40% vs. 0%, OR 34.5, 95% CI: 1.9–630; P=0.01). Microsatellite instability (36% vs. 4%, OR 19.8, 95% CI: 2.2–180; P=0.008) and prior tobacco exposure (44% vs. 16%, OR 4.1, 95% CI: 1.1–15.6, P=0.04) were associated with a favorable prognosis. Durable responses to MAPK-targeted therapies and immunotherapy were noted in the favorable group.ConclusionsA small fraction of patients with BRAF^V600E mutated metastatic CRC can achieve excellent long-term survival which belies conventional context and is driven by either surgical metastectomy or by systemic treatment options. While poor overall prognosis remains the recognized outcome for most patients with BRAF^V600E mutated metastatic CRC, it is possible that few may achieve exceptionally favorable survival.     

Plasmodium falciparum synthetic LbL microparticle vaccine elicits protective neutralizing antibody and parasite-specific cellular immune responses

Epitopes of the circumsporozoite (CS) protein of Plasmodium falciparum, the most pathogenic species of the malaria parasite, have been shown to elicit protective immunity in experimental animals and human volunteers. The mechanisms of immunity include parasite-neutralizing antibodies that can inhibit parasite motility in the skin at the site of infection and in the bloodstream during transit to the hepatocyte host cell and also block interaction with host cell receptors on hepatocytes. In addition, specific CD4+ and CD8+ cellular mechanisms target the intracellular hepatic forms, thus preventing release of erythrocytic stage parasites from the infected hepatocyte and the ensuing blood stage cycle responsible for clinical disease. An innovative method for producing particle vaccines, layer-by-layer (LbL) fabrication of polypeptide films on solid CaCO₃ cores, was used to produce synthetic malaria vaccines containing a tri-epitope CS peptide T1BT* comprising the antibody epitope of the CS repeat region (B) and two T-cell epitopes, the highly conserved T1 epitope and the universal epitope T*. Mice immunized with microparticles loaded with T1BT* peptide developed parasite-neutralizing antibodies and malaria-specific T-cell responses including cytotoxic effector T-cells. Protection from liver stage infection following challenge with live sporozoites from infected mosquitoes correlated with neutralizing antibody levels. Although some immunized mice with low or undetectable neutralizing antibodies were also protected, depletion of T-cells prior to challenge resulted in the majority of mice remaining resistant to challenge. In addition, mice immunized with microparticles bearing only T-cell epitopes were not protected, demonstrating that cellular immunity alone was not sufficient for protective immunity. Although the microparticles without adjuvant were immunogenic and protective, a simple modification with the lipopeptide TLR2 agonist Pam₃Cys increased the potency and efficacy of the LbL vaccine candidate. This study demonstrates the potential of LbL particles as promising malaria vaccine candidates using the T1BT* epitopes from the P. falciparum CS protein.     

Triple falx cerebelli associated with two aberrant venous sinuses in the floor of posterior cranial fossa

During regular dissection classes, we came across tripled falx cerebelli in a male cadaver. The main (middle) falx cerebelli was large and was attached to the internal occipital crest. It contained the occipital sinus. There were two smaller folds (right and left), one on either side of the falx cerebelli. There were two aberrant venous sinuses; each one connecting the ipsilateral sigmoid and transverse sinuses with each other. The complex dural-venous variation reported here is seldom reported in the literature. Knowledge of such variation is important for neurosurgeons and neuroradiologists as these aberrant folds could cause haemorrhage during suboccipital approaches or may lead to erroneous interpretation during imaging of the posterior cranial fossa.     

Pellagra in a child–A rare entity

This case has been presented as pellagra, which is very rare in children. Pellagra is due dietary deficiency of niacin. Usually seen in alcoholics, malabsorption syndromes occur very rarely in children. A 11-y-old girl presented with well-defined, hyperpigmented, hyperkeratotic, symmetrical, thick scaly plaques surrounded by erythema on the dorsum of the hands, arms, feet, legs up to knees, and along the sides of the neck. The child was given 100 mg of Nicotinamide. Skin lesions resolved rapidly with the treatment and the child improved.