In situ generation of copper(â ¡)/diethyldithiocarbamate complex through tannic acid/copper(â ¡) network coated hollow mesoporous silica for enhanced cancer chemodynamic therapy.

The Cu2+ complex formed by the coordination of disulfiram (DSF) metabolite diethyldithiocarbamate (DTC), Cu(DTC)2, can effectively inhibit tumor growth. However, insufficient Cu2+ levels in the tumor microenvironment can impact tumor-suppressive effects of DTC. In this study, we proposed a Cu2+ and DSF tumor microenvironment-targeted delivery system. This system utilizes hollow mesoporous silica (HMSN) as a carrier, after loading with DSF, encases it using a complex of tannic acid (TA) and Cu2+ on the outer layer. In the slightly acidic tumor microenvironment, TA/Cu undergoes hydrolysis, releasing Cu2+ and DSF, which further form Cu(DTC)2 to inhibit tumor growth. Additionally, Cu2+ can engage in a Fenton-like reaction with H2O2 in the tumor microenvironment to form OH, therefore, chemodynamic therapy (CDT) and Cu(DTC)2 are used in combination for tumor therapy. In vivo tumor treatment results demonstrated that AHD@TA/Cu could accumulate at the tumor site, achieving a tumor inhibition rate of up to 77.6 %. This study offers a novel approach, circumventing the use of traditional chemotherapy drugs, and provides valuable insights into the development of in situ tumor drug therapies.

pH/glutathione dual-responsive copper sulfide-coated organic mesoporous silica for synergistic chemo-photothermal therapy.

Nanodrug delivery systems (NDSs), such as mesoporous silica, have been widely studied because of their high specific surface area, high loading rate, and easy modification; however, they are not easily metabolized and excreted by the human body and may be potentially harmful. Hence, we aimed to examine the synergistic anti-tumor effects of ex vivo chemo-photothermal therapy to develop a rational and highly biocompatible treatment protocol for tumors. We constructed a biodegradable NDS using organic mesoporous silica with a tetrasulfide bond structure, copper sulfide core, and folic acid-modified surface (CuS@DMONs-FA-DOX-PEG) to target a tumor site, dissociate, and release the drug. The degradation ability, photothermal conversion ability, hemocompatibility, and in vitro and in vivo anti-tumor effects of the CuS@DMONs-FA-DOX-PEG nanoparticles were evaluated. Our findings revealed that the nanoparticles encapsulated in copper sulfide exhibited significant photothermal activity and optimal photothermal conversion rate. Further, the drug was accurately delivered and released into the target tumor cells, annihilating them. This study demonstrated the successful preparation, safety, and synergistic anti-tumor effects of chemo-photothermal therapeutic nanomaterials.

Gastrointestinal histoplasmosis complicating pediatric Crohn disease: A case report and review of literature.

BACKGROUND: Infection with Histoplasma capsulatum (H. capsulatum) can lead to disseminated disease involving the gastrointestinal tract presenting as diffuse abdominal pain and diarrhea which may mimic inflammatory bowel disease (IBD). CASE SUMMARY: We report a case of 12-year-old boy with presumptive diagnosis of Crohn disease (CD) that presented with several months of abdominal pain, weight loss and bloody diarrhea. Colonoscopy showed patchy moderate inflammation characterized by erythema and numerous pseudopolyps involving the terminal ileum, cecum, and ascending colon. Histologic sections from the colon biopsy revealed diffuse cellular infiltrate within the lamina propria with scattered histiocytic aggregates, and occasional non-necrotizing granulomas. Grocott-Gomori's Methenamine Silver staining confirmed the presence of numerous yeast forms suggestive of Histoplasma spp., further confirmed with positive urine Histoplasma antigen (6.58 ng/mL, range 0.2-20 ng/mL) and serum immunoglobulin G antibodies to Histoplasma (35.9 EU, range 10.0-80.0 EU). Intravenous amphotericin was administered then transitioned to oral itraconazole. Follow-up computed tomography imaging showed a left lower lung nodule and mesenteric lymphadenopathy consistent with disseminated histoplasmosis infection. CONCLUSION: Gastrointestinal involvement with H. capsulatum with no accompanying respiratory symptoms is exceedingly rare and recognition is often delayed due to the overlapping clinical manifestations of IBD. This case illustrates the importance of excluding infectious etiologies in patients with "biopsy-proven" CD prior to initiating immunosuppressive therapies. Communication between clinicians and pathologists is crucial as blood cultures and antigen testing are key studies that should be performed in all suspected cases of histoplasmosis to avoid misdiagnosis and inappropriate treatment.

Tumor Genomic Profiling to Determine Tissue Origin of Cancers of Unknown Primary: A Single Institute Experience With its Utility and Impact on Patient Management.

Tumor genomic profiling represents a promising tool in diagnosis and management of cancer of unknown primary. We report our experience on the impact of genomic profiling in elucidating primary tumor site, correlation with pathologic findings and patient management. Tissue or cytology specimens from 22 cancers of unknown primary were referred for genomic profiling. Reports were available to review in 18 cases; 3 samples were inadequate for analysis. Of the remaining 15 cases, primary tumor site was suggested in 12 cases (80%), whereas it remained indeterminate in 3 (20%). Of the 12 cases, molecular profiling was concordant with light microscopy findings in 3 patients, whereas in 2 cases molecular testing identified a sarcoma, contradicting light microscopy and immunohistochemistry findings. The suggested primary was confirmed by additional immunohistochemistry in 1 case and by endoscopic biopsy in another. In 5 cases, follow-up biopsy or additional testing were not considered necessary for patient management. Three patients received palliative care and 12 received various chemotherapy regimens. Five patients died within a year, whereas 9 were alive more than a year after diagnosis, 3 of who were alive >3 years after diagnosis. In conclusion, genomic profiling helped confirm the original diagnosis and suggested primary sites in two third of our cases. Although many patients may be at a disease stage too advanced to withstand further investigations or underg aggressive therapy, molecular testing improves diagnostic accuracy and may thus assist in selection of the most appropriate therapy.

Evaluating mismatch repair deficiency for solid tumor immunotherapy eligibility: immunohistochemistry versus microsatellite molecular testing.

While many landmark solid tumor immunotherapy studies show clinical benefits for solid tumors with high microsatellite instability (MSI-H) and mismatch repair deficiency (dMMR), the methodologies focus only on confirmatory polymerase chain reaction (PCR) testing for MSI-H. Because some tumors are either dMMR or MSI-H but not the other, clinicians must choose between two testing methods for a broad patient population. We investigated the level of correlation between MMR protein immunohistochemistry (IHC) and microsatellite PCR testing results in 62 cancer patients. Thirty-five of the 62 cases (56.5%) were MSI-H by PCR, whereas 35 (56.5%) were dMMR by IHC. MMR IHC results correlated well with MSI PCR in 32 co-positive cases (91.4%) and 24 co-negative cases (88.9%). Six discrepant cases (9.7%) were identified, among which three were MSI-H and MMR intact, and three were dMMR and microsatellite stable. The results of this study highlight the implications of dMMR/MSI testing strategies on precision oncology. Co-testing with both MMR IHC and MSI PCR may be an effective screening strategy for evaluating immunotherapy eligibility status for solid tumors.

Fabrication of a novel low-cost superoleophilic nonanyl chitosan-poly (butyl acrylate) grafted copolymer for the adsorptive removal of crude oil spills.

A novel superoleophilic-hydrophobic nonanyl chitosan-poly (butyl acrylate) grafted copolymer was fabricated as a low-cost oil-adsorbent. Chitosan (CS) was coupled with a hydrophobic nonanal (N) to form nonanyl chitosan (NCS) schiff base, and followed by grafting with butyl acrylate monomers (ButA). The grafted copolymer was characterized by FTIR, TGA and SEM tools. The grafting percent was augmented and reached 88.5% with increasing ButA concentration up to 156 mM. Moreover, measurements of contact angle proved the superoleophilic character of NCS-g-poly (ButA) copolymer with an oil-contact angle 31°. Factors affecting the removal process such as contact time, oil type, oil dose, adsorbent dose, temperature and agitation speed were optimized. An increment in the oil removal (%) was observed with increasing the oil viscosity in the order of gasoil < mobil-1 oil < light crude oil < heavy crude oil. Besides, the adsorption process followed the pseudo-second order model and the equilibrium data were sufficiently fitted with the Langmuir model with a maximum adsorption capacity 108.79 g/g at 25 °C. Thermodynamic parameters computed from Van't Hoff plot confirmed the process to be exothermic, favorable and spontaneous. The results nominate the superoleophilic adsorbent as a potential oil- adsorbent for petroleum oil spills removal.

Fabrication of biodegradable gelatin/chitosan/cinnamaldehyde crosslinked membranes for antibacterial wound dressing applications.

This study intends to fabricate new biodegradable and antimicrobial membranes based on crosslinked gelatin/chitosan biopolymers. Cinnamaldehyde was incorporated into membranes for boosting their antimicrobial activities. FTIR spectroscopy and electronic spectrum analysis were used to prove their chemical structures, while SEM and TGA analysis were applied to investigate the morphological changes and the thermal properties of the crosslinked membranes. Moreover, ion exchange capacity, wettability and mechanical analysis were also conducted to get more information about the physicochemical properties for the developed membranes. Four different types of bacteria have been used for studying the antibacterial activities of the crosslinked membranes (one gram-positive and three gram-negative bacteria). The results showed a significant augmentation in the inhibition percent with increasing cinnamaldehyde content in the membrane matrix. Besides, hemocompatibility, biodegradability, and cytotoxicity studies were performed and the findings emphasized that the as-fabricated biodegradable gelatin/chitosan/cinnamaldehyde membranes could be efficiently used as antibacterial dressers for ameliorating the wound healing.

Fabrication of magnetic bentonite/carboxymethyl chitosan/sodium alginate hydrogel beads for Cu (II) adsorption.

In this work, composite hydrogel beads based on magnetic bentonite/carboxymethyl chitosan/sodium alginate (Mag-Ben/CCS/Alg) were fabricated and their ability to adsorb copper ions in water was studied. The structure and properties of the composite were characterized via SEM, FTIR, XPS, TGA, VSM, and Zeta potential tests. The effects of the adsorbent dosage, adsorption time, pH, temperature, and initial concentration of Cu(II) on the adsorption results were studied. The results showed that Mag-Ben/CCS/Alg reached equilibrium after 90 min of adsorption, the removal rate of Cu(II) was 92.62 ±â€¯0.39%, and the maximum adsorption capacity was 56.79 mg/g (30 °C). The removal rate of Cu(II) by Mag-Ben/CCS/Alg still remained above 80% after recycling four times. The adsorption process of Cu(II) by Mag-Ben/CCS/Alg occurred in accordance with the quasi-second-order kinetic model and Langmuir adsorption isotherm. The adsorption process was spontaneous and endothermic.

Dual-layered pH-sensitive alginate/chitosan/kappa-carrageenan microbeads for colon-targeted release of 5-fluorouracil.

A new pH-sensitive drug carrier based on alginate (Alg), chitosan (Cs), and kappa-carrageenan (kC) marine biopolymers was developed, comprising a dual-layered polyelectrolyte complexes microbead structure. Fourier-transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM) were used to investigate the structures, thermal stability, and morphological changes, respectively, of the microcapsules we developed. In the intestinal environment (pH 7.4), the stability and swelling of Alg microbeads were enhanced after generation of the dual-layered polyelectrolyte complexes. The in vitro release profiles of 5-fluorouracil under simulated GI conditions were also examined. At gastric pH (1.2), the cumulative 5-FU release percentage was decreased by introduction of the additional kC layer from 14% in Alg/Cs microbeads to 7% in the dual-layered Alg/Cs/kC microbeads. Additionally, the release profiles were greatly improved under simulated intestinal and colon conditions. Finally, the microbeads were all biodegradable and showed no cytotoxicity in Chang liver cells. Our results clearly indicate that the dual-layer pH-sensitive Alg/Cs/kC microbeads could be used effectively for the targeted delivery of anticancer drugs to the colon.

pH-sensitive ZnO/carboxymethyl cellulose/chitosan bio-nanocomposite beads for colon-specific release of 5-fluorouracil.

To develop relatively green and ecofriendly smart vehicles for colon-specific drug delivery, carboxymethyl cellulose (CMC) and chitosan (CS) pH-sensitive biopolymers were used in this study. To overcome the weaknesses of CMC carriers, such as poor mechanical performance and an explosive drug release, zinc oxide (ZnO) nanoparticles were incorporated into CMC beads and then coated with a CS layer via a self-assembly technique to form core-shell polyelectrolyte complexes. An anticancer drug, 5-fluorouracil (5-FU), used as a model drug, was loaded into ZnO/CMC/CS bio-nanocomposite beads. Fourier transform infrared spectroscopy, scanning and transmission electron microscopy, and thermogravimetric analysis were used to characterize the chemical structure, morphological changes, and thermal properties of the developed drug carrier, respectively. By studying their swelling and in vitro 5-FU release profiles under simulated gastrointestinal conditions, the pH sensitivity of the developed bio-nanocomposite hydrogel beads could be investigated. The obtained beads with reduced porosity could effectively encapsulate 5-FU and showed self-sustained release behavior depending on the concentrations of CMC, CS, and ZnO nanoparticles. The developed beads also demonstrated a capacity for biodegradation. The results indicated that the ZnO/CMC/CS bio-nanocomposite beads exhibited pH-sensitivity and could be applied efficiently as biodegradable carriers for colon-specific 5-FU delivery.

Fabrication of tetraethylenepentamine functionalized alginate beads for adsorptive removal of Cr (VI) from aqueous solutions.

In this study, an innovative adsorbent based on tetraethylenepentamine (TEPA) functionalized alginate (Alg) beads (TEPA-Alg) was developed for the adsorptive removal of Cr (VI) from aqueous solutions. Chemical modification of alginate surface was carried out using p-benzoquinone (PBQ) as a coupling agent followed by functionalization with TEPA. The prepared functionalized beads were characterized using FTIR, TGA, SEM, and XPS tools. Results showed that the ion exchange capacity (IEC) significantly increased from 6.34 to 10.32 meq g-1 with increasing TEPA concentration up to 0.05 M. Furthermore, removal (%) of Cr (VI) increased gradually from 38 to 86% with rising TEPA concentration from 0.0125 M to 0.05 M. While only 22% was recorded using native alginate beads. The gained equilibrium data were fitted to Langmuir isotherm model with maximum adsorption capacity ~ 77 mg/g and the adsorption kinetics were well-expressed by pseudo-first-order model. Reusability studies showed good adsorption properties after 5 consecutive cycles. Results achieved by this study imply that the prepared functionalized TEPA-Alg beads could be efficiently utilized for the removing Cr (VI) ions from their aqueous solutions.

Efficient adsorption of diclofenac sodium from aqueous solutions using magnetic amine-functionalized chitosan.

In this study, we prepared a magnetic composite based on amine-functionalized chitosan (aminochitosan; AmCS) and Fe3O4 to remove diclofenac sodium (DS) from water. The fabricated AmCS@Fe3O4 composite was characterized using Fourier-transform infrared spectroscopy, transmission electron microscopy, scanning electron microscopy, vibrating sample magnetometry, X-ray diffraction, and thermogravimetric analysis. Furthermore, we investigated the influence of pH, initial DS concentration, and adsorbent dosage on the adsorption of DS. Through thermodynamic analysis, we found that the data corresponded with the Langmuir adsorption isotherm model. The maximum adsorption capacity reached 469.48 mg g-1, and the adsorption process followed the pseudo-second-order kinetic model. Finally, the AmCS@Fe3O4 composite retained good adsorption characteristics after four consecutive cycles, with removal efficiency exceeding 70%. Therefore, the developed adsorbent could be used for efficient adsorptive removal of trace drugs and personal care products from water bodies.

Adsorptive removal of cationic methylene blue dye using carboxymethyl cellulose/k-carrageenan/activated montmorillonite composite beads: Isotherm and kinetic studies.

In the present study, new composite beads based on carboxymethyl cellulose (CMC)/k-carrageenan (kC)/activated montmorillonite (AMMT) were prepared for adsorptive removal of cationic methylene blue (MB) as a dye model. The structure and morphology of the composite beads were investigated by FT-IR and SEM, while the thermal properties were tested using TGA. Factors affecting the removal percent of MB such as CMC/kC/AMMT ratios, initial MB concentration, pH medium, adsorbent dosage, solution temperature, and agitation speed were also explored. Results demonstrated that MB removal (%) exceeded 92% after 120 min using CMC/kC/AMMT (1:1:0.4 ratio) compared to 69% in case of free AMMT beads. Moreover, data obtained from isotherm studies were fitted well to Langmuir model (R2=0.999), and the kinetics of adsorption followed pseudo-second order model. Finally, the composite beads showed good reusability for MB dye removal with high efficiency. Results obtained from this study suggest that the prepared composite beads could be applied effectively for removing cationic dyes from aqueous solutions.

Fine needle aspiration cytology of hepatic metastases of neuroendocrine tumors: A 20-year retrospective, single institutional study.

BACKGROUND: Fine needle aspiration (FNA) is considered an excellent technique for documenting metastatic neuroendocrine tumors (NETs). This study aims to evaluate the accuracy of FNA in diagnosing metastatic NETs to the liver and determining the grade and origin of these metastases. METHODS: Our laboratory information system was searched from 1997 to 2016 to identify all cases of metastatic NETs to the liver that were sampled by FNA. The cytopathology and surgical pathology reports as well as the patients' electronic medical records were reviewed. The cytohistologic type and grade of the metastatic NETs, as well as the site of the patient's primary were recorded. RESULTS: High-grade NETs, including small cell and poorly differentiated neuroendocrine carcinomas, constituted 62% (167/271) of the cases, while low-grade NETs, including well differentiated NET (grade1 and grade 2), pheochromocytomas, paragangliomas, and carcinoid tumors of lung, constituted 38% (104/271) of cases. The most common diagnosis was metastatic small cell carcinoma accounting for 45% (122/271) of cases. The most common primary sites were lung (44%; 119/271) followed by pancreas (19%; 51/271). The FNA diagnosis was confirmed by histopathology in 121 cases that had a concurrent biopsies or resection specimens. CONCLUSIONS: FNA is an accurate method for diagnosing metastatic NETs to the liver. There were significantly more high-grade (62%) than low-grade (38%) metastatic NETs to the liver. In our practice, lung (44%) and pancreas (19%) were the most common primary sites of metastatic NETs involving the liver. In 16% of the cases, a primary site could not be established.

Adsorption of Pb(II) from fish sauce using carboxylated cellulose nanocrystal: Isotherm, kinetics, and thermodynamic studies.

In the present study, a new adsorbent based on carboxylated cellulose nanocrystal (CCN) was developed for the adsorption of Pb(II) from fish sauce. The prepared adsorbent material was characterized by zeta potential, FT-IR, XRD, and XPS tools. The changes in the morphological structure of the developed CCN surface were evidenced by SEM and TEM. The favorable adsorption conditions were selected by studying the contact time, initial concentration, temperature, and concentration of the used glutamic acid and NaCl. The results indicated that the Langmuir isotherm model agrees very well with experimental adsorption data (R2=0.9962) with a maximum adsorption capacity 232.56mg/g of Pb(II) at 293.2K. Additionally, data of the adsorption kinetics follow the pseudo-second-order kinetics (R2>0.9990). On the other hand, the thermodynamics studies show that the adsorption process is spontaneous and endothermic. Furthermore, the developed CCN could be regenerated using acid treatment with a good reusability for Pb(II) adsorption. The results clearly indicated that the synthesized CCN could be effectively applied as a new material for Pb(II) adsorption from fish sauce solutions.

Development of amphoteric alginate/aminated chitosan coated microbeads for oral protein delivery.

A new amphoteric biopolymer carrier based on alginate and aminated chitosan coated microbeads (Alg/AmCS) was developed and characterized for bovine serum albumin (BSA) protein delivery. The amphoteric character was investigated through studying the swelling and in vitro BSA release behaviors of the developed microbeads in simulated gastric (SGF; pH1.2), intestinal (SIF; pH6.8), and colonic (SCF; pH7.4) fluids. The pH sensitivity was found to depend on the amount of AmCS in the coating medium. The results were interpreted from the view of the individual pH sensitivity of alginate and aminated chitosan in addition to the ionic interaction between them under the studied pHs. Besides; it was found that the BSA loading efficiency (LE) exceeded 82% regardless of the initial concentration of BSA. The released amount of BSA reached approximately 63% and 86% in SIF and SCF, respectively, using 0.25% AmCS. The stability of alginate microbeads in SCF was improved with increasing AmCS concentration in the coating medium up to 2%. Furthermore, the developed microbeads demonstrated their ability for biodegradation in addition to their antibacterial activities against selected bacterial strains. The results clearly suggested that Alg/AmCS coated microbeads could be suitable carriers for site-specific protein delivery in the intestinal and colon tracts.

Risk factors of low birth weight at three hospitals in Khartoum State, Sudan.

The aim of this study was to determine the percentage of women who give birth to low birth weight (LBW) children and to study the association of the different risk factors with LBW in three of large hospitals in Khartoum State, Sudan. This was a cross sectional study of 381 women. Three groups: 151, 130 and 100 women, who gave birth to live children, were selected from Alsuadi Teaching Hospital, Khartoum Teaching Hospital and Alribat University Hospital, respectively. Data were collected through structured interviews and the birth weights were recorded as measured by midwives. Uni-Multi variate analysis of the data was performed using SPSS 19. Permissions were taken from hospital administration and the participants before the conduction of the research. 13% of live born children were of low birth weight. The main risk factors for low birth weight in the study were the lack of adequate education (OR= 1.9) gestational age (OR= 5.5), type of pregnancy (OR= 9.6), presence of hypertension (OR= 3.6), renal disease (OR= 2.1), bleeding during pregnancy (OR= 6.1) and presence of moderate or severe anemia (OR= 3.19). While Adequacy of antenatal care (ANC) visits, presence of diabetes mellitus during pregnancy, smoking and malaria in the first three trimesters, presence of previous children and spacing were all found to be statistically not significant risk factors. Many of the risk factors are modifiable and can be prevented by improvement of the health care during pregnancy.