Beyond cyclopamine: Targeting Hedgehog signaling for cancer intervention.

Hedgehog (Hh) signaling plays a significant role in embryogenesis and several physiological processes, such as wound healing and organ homeostasis. In a pathological setting, it is associated with oncogenesis and is responsible for disease progression and poor clinical outcomes. Hedgehog signaling mediates downstream actions via Glioma Associated Oncogene Homolog (GLI) transcription factors. Inhibiting Hh signaling is an important oncological strategy in which inhibitors of the ligands SMO or GLI have been looked at. This review briefly narrates the Hh ligands, signal transduction, the target genes involved and comprehensively describes the numerous inhibitors that have been evaluated for use in various neoplastic settings.

Association between sarcopenia and postoperative complications in patients undergoing surgery for gastrointestinal or hepato-pancreatico-biliary cancer.

BACKGROUND AND OBJECTIVES: Despite surgical advances, postoperative complications persist, affecting oncologic outcomes and increasing treatment costs. It is important to identify a marker that can predict postoperative complications, which can help prehabilitate patients before surgery. This study evaluated sarcopenia as a predictive marker of postoperative complications in patients undergoing surgery for gastrointestinal (GI) or hepato-pancreatico-biliary (HPB) cancer. METHODS: Sarcopenia was assessed using the skeletal muscle index at the third lumbar vertebra on abdominal computed tomography. The predictive ability of sarcopenia was evaluated by adjusting for other clinicopathological factors. RESULTS: Of the 210 patients, 81 (38.57%) were sarcopenic. The overall morbidity and mortality were 33.81% and 2.86%, respectively. Major complications (Clavien-Dindo Grade ≥ III) were observed in 10.95% patients and sarcopenic patients were significantly more likely to develop major complications (p = 1.42 × 10-10 ). Sarcopenia (p = 6.13 × 10-6 ; odds ratio = 12.29) independently predicted postoperative complications and prolonged hospital stay (p = 0.01). CONCLUSION: Sarcopenia objectively predicted the development of postoperative complications and prolonged hospital stay in patients undergoing surgery for GI or HPB cancer. This may facilitate the prehabilitation of patients planned for surgery to reduce the risk of complications.

Nanostructured Metal Phosphide Based Catalysts for Electrochemical Water Splitting: A Review.

Amongst various futuristic renewable energy sources, hydrogen fuel is deemed to be clean and sustainable. Electrochemical water splitting (EWS) is an advanced technology to produce pure hydrogen in a cost-efficient manner. The electrocatalytic hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) are the vital steps of EWS and have been at the forefront of research over the past decades. The low-cost nanostructured metal phosphide (MP)-based electrocatalysts exhibit unconventional physicochemical properties and offer very high turnover frequency (TOF), low over potential, high mass activity with improved efficiency, and long-term stability. Therefore, they are deemed to be potential electrocatalysts to meet practical challenges for supporting the future hydrogen economy. This review discusses the recent research progress in nanostructured MP-based catalysts with an emphasis given on in-depth understanding of catalytic activity and innovative synthetic strategies for MP-based catalysts through combined experimental (in situ/operando techniques) and theoretical investigations. Finally, the challenges, critical issues, and future outlook in the field of MP-based catalysts for water electrolysis are addressed.

The role of squash cytology in rapid on-site adequacy checking and rapid diagnosis in image-guided gun biopsy at a tertiary cancer center.

OBJECTIVE: To evaluate the role of squash cytology in rapid on-site adequacy checking (ROSAC) of image-guided gun biopsy and to determine its diagnostic accuracy at a tertiary cancer center. STUDY DESIGN: This was a prospective study on 183 patients undergoing image-guided biopsy. Squash smears were prepared from biopsy cores and checked for adequacy by cytotechnologists. When adequate, more cores were sampled from the same area for histopathology. If inadequate, the procedure was repeated at the same sitting on a different area. The squash smears were reported by cytopathologists within 4 h after staining with conventional Papanicoloau stain. The results were compared with the final histopathology report. RESULTS: The sampling was representative in 95.6% cases with concordance for adequacy in 97.3% cases. The sensitivity, specificity, positive predictive value and negative predictive value of squash cytology for diagnosis of the lesion were 99.4, 92.7, 97.7 and 97.4%, respectively. CONCLUSIONS: Squash cytology is an ideal and cost-effective technique for ROSAC of image-guided biopsies, which ensures adequacy, avoids repeat procedures and prevents delay in diagnosis. It can be effectively performed by trained cytotechnologists in radiology clinics. Squash cytology is also a cost-effective tool offering rapid diagnosis which expedites planning of treatment.

Advances in Understanding and Management of Erdheim-Chester Disease.

Erdheim Chester Disease (ECD) is a rare histiocytic disorder marked by infiltration of organs with CD68+ histiocytes. ECD stems from mutations of BRAF and MAP2K1 in hematopoietic stem and progenitor cells (HSPCs), which further differentiate into monocytes and histiocytes. Histopathology reveals lipid-containing histiocytes, which test positive for CD68 and CD133 in immunohistochemistry. Signs and symptoms vary and depend on the organ/s of manifestation. Definitive radiological results associated with ECD include hairy kidney, coated aorta, and cardiac pseudotumor. Treatment options primarily include anti-cytokine therapy and inhibitors of BRAF and MEK signaling.

Gelation and large thermoresponse of cranberry-based xyloglucan.

Cranberry waste contains potentially valuable components, such as proanthocyanidins, flavanols, and xyloglucan. Highly-purified xyloglucan (XG) from cranberries were studied through steady and oscillatory shear rheology at various concentrations and temperatures. At room temperature, an apparent yield stress is observed and the storage modulus exceeds the loss modulus ( [Formula: see text] ) for concentrations of 0.5 wt% and higher, indicating that the XG solution has formed a physical hydrogel. Thermoresponsive gelation is observed with a five-order of magnitude increase in shear moduli as it undergoes a weak to strong gel transition around 52 °C. The gelation time was 5 min with an observed storage moduli up to 3500 Pa. Cranberry-based XG exhibits thermoresponsive behavior at concentrations as low as 0.1 wt% (w/v), which is significantly lower than prior gelation studies of XG from other sources. The formation of a weak gel at room temperature and large storage moduli observed at room temperature is likely associated with the low level of impurities and small amount of galactose present in the XG chains.

Endovascular Management of Thenar-Hypothenar Aneurysms: Two Case Reports and Review of Literature.

Thenar-hypothenar arterial aneurysms are rare, presenting as either true aneurysms or pseudoaneurysms. Traditionally, surgical repair has been the mainstay of treatment for these aneurysms, with only isolated cases of endovascular management reported. In this study, we describe two cases of thenar-hypothenar aneurysms successfully managed with coil embolization, accompanied by a brief literature review. Our findings suggest that endovascular management is a feasible treatment option for these rare aneurysms.

Properties of SiCN Films Relevant to Dental Implant Applications.

The application of surface coatings is a popular technique to improve the performance of materials used for medical and dental implants. Ternary silicon carbon nitride (SiCN), obtained by introducing nitrogen into SiC, has attracted significant interest due to its potential advantages. This study investigated the properties of SiCN films deposited via PECVD for dental implant coatings. Chemical composition, optical, and tribological properties were analyzed by adjusting the gas flow rates of NH3, CH4, and SiH4. The results indicated that an increase in the NH3 flow rate led to higher deposition rates, scaling from 5.7 nm/min at an NH3 flow rate of 2 sccm to 7 nm/min at an NH3 flow rate of 8 sccm. Concurrently, the formation of N-Si bonds was observed. The films with a higher nitrogen content exhibited lower refractive indices, diminishing from 2.5 to 2.3 as the NH3 flow rate increased from 2 sccm to 8 sccm. The contact angle of SiCN films had minimal differences, while the corrosion rate was dependent on the pH of the environment. These findings contribute to a better understanding of the properties and potential applications of SiCN films for use in dental implants.

Therapeutic response to radiofrequency ablation of neoplastic lesions: FDG PET/CT findings.

Ablation of neoplastic lesions by using radiofrequency energy is gaining popularity in clinical practice because of the minimally invasive nature of radiofrequency ablation (RFA). Primary and secondary tumors of the liver and lung are treated with RFA when surgery is precluded because of comorbidity. Benign bone tumors are also treated with RFA to relieve pain and prevent further tumor growth. Differentiation between postablation tissue changes and residual disease is difficult with morphologic imaging modalities such as ultrasonography, computed tomography (CT), and magnetic resonance (MR) imaging, thus limiting the use of these modalities to detection of residual disease early after RFA. Fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) is a functional imaging modality that can be used to study the effects and efficacy of RFA. Lesions that show increased FDG uptake at PET become completely photopenic immediately after RFA, a finding that is suggestive of the completeness of ablation. Focal areas of increased FDG uptake within the ablated zone are suggestive of residual disease. Reactive tissue changes such as inflammation are depicted in the periphery of the ablated lesion and show a uniform low-grade FDG uptake, which can be differentiated from the focal, nodular intense uptake in areas of residual disease. Use of combined FDG PET/CT to detect residual disease early after RFA allows ablation to be repeated, if necessary, to obtain the maximum therapeutic benefit. Note that FDG uptake in the complications sometimes associated with RFA can be a cause of potential false-positive PET results.

Objective assessment of swallowing function after definitive concurrent (chemo)radiotherapy in patients with head and neck cancer.

The aim of this study was to objectively assess swallowing function and factors impacting it after curative intent definitive (chemo)radiotherapy (CRT) for head and neck squamous cell carcinoma (HNSCC). Swallowing function was studied in a cohort of 47 patients with locoregionally advanced (T1-4, N0-3) HNSCC treated with definitive CRT. Objective assessment of swallowing function was done using modified barium swallow (MBS) at baseline (pre-CRT) and subsequent follow-ups. Scoring of MBS was done using penetration-aspiration scale (PAS). Abnormal swallowing was defined in terms of incidence and severity of penetration-aspiration, pharyngeal residue, postural change, and regurgitation. Aspiration, residual, postural change, and regurgitation were present on baseline pre-CRT assessment in 9 (19%), 11 (23%), 10 (21%), and 5 (10%) patients that increased to 11 (29%), 11 (29%), 12 (32%), and 10 (26%) patients, respectively, at 6-month post-CRT evaluation. The proportion of patients with high PAS scores (3-7) increased from 27% at baseline to 37% at 6-month post-CRT evaluation. Among patients (n = 34) with low PAS scores (≤2) at baseline, additional impairment of swallowing function was seen in 53 and 46% at 2- and 6-month assessment, respectively. Residue (44%) and aspiration (18%) domains were impaired in a higher proportion of patients after CRT. Thin and thick barium had higher aspiration and residue function impairment, respectively. Patients with pre-CRT poor subjective swallowing function (P = 0.004), hypopharyngeal primary (P = 0.05), and large tumor volume (P = 0.05) had significantly worse objective swallowing function at baseline as demonstrated by pretreatment PAS scores. This study provides useful information regarding patterns of objective swallowing dysfunction in patients treated with definitive (chemo)radiotherapy. There is significant impairment of objective swallowing function in all domains following CRT, with residue and aspiration domains being affected most significantly.

CdS decorated MnWO4 nanorod nanoheterostructures: a new 0D-1D hybrid system for enhanced photocatalytic hydrogen production under natural sunlight.

Constructing a heterostructure is an effective strategy to reduce the electron-hole recombination rate, which enhances photocatalytic activity. Here, we report a facile hydrothermal method to grow CdS nanoparticles on MnWO4 nanorods and their photocatalytic hydrogen generation under solar light. A structural study shows the decoration of hexagonal CdS nanoparticles on monoclinic MnWO4. Morphological studies based on FE-TEM analysis confirm the sensitization of CdS nanoparticles (10 nm) on MnWO4 nanorods of diameter-35 nm with mean length ∼100 nm. The lower PL intensity of MnWO4 was observed with an increasing amount of CdS nanoparticles, which shows inhibition of the charge carrier recombination rate. A CdS@MnWO4 narrow band gap semiconductor was employed for photocatalytic hydrogen generation from water under solar light and the highest amount of hydrogen, i.e. 3218 µmol h-1 g-1, is obtained which is 21 times higher than that with pristine MnWO4. The enhanced photocatalytic activity is ascribed to the formation of a CdS@MnWO4 nanoheterostructure resulting in efficient spatial separation of photogenerated electron-hole pairs due to vacancy defects. More significantly, direct Z-scheme electron transfer from MnWO4 to CdS is responsible for the enhanced hydrogen evolution. This work signifies that a CdS decorated MnWO4 nanoheterostructure has the potential to improve the solar to direct fuel conversion efficiency.

Efficient solar light-driven hydrogen generation using an Sn3O4 nanoflake/graphene nanoheterostructure.

Herein, we report Sn3O4 and Sn3O4 nanoflake/graphene for photocatalytic hydrogen generation from H2O and H2S under natural "sunlight" irradiation. The Sn3O4/graphene composites were prepared by a simple hydrothermal method at relatively low temperatures (150 °C). The incorporation of graphene in Sn3O4 exhibits remarkable improvement in solar light absorption, with improved photoinduced charge separation due to formation of the heterostructure. The highest photocatalytic hydrogen production rate for the Sn3O4/graphene nanoheterostructure was observed as 4687 µmol h-1 g-1 from H2O and 7887 µmol h-1 g-1 from H2S under natural sunlight. The observed hydrogen evolution is much higher than that for pure Sn3O4 (5.7 times that from H2O, and 2.2 times from H2S). The improved photocatalytic activity is due to the presence of graphene, which acts as an electron collector and transporter in the heterostructure. More significantly, the Sn3O4 nanoflakes are uniformly and parallel grown on the graphene surface, which accelerates the fast transport of electrons due to the short diffusion distance. Such a unique morphology for the Sn3O4 along with the graphene provides more adsorption sites, which are effective for photocatalytic reactions under solar light. This work suggests an effective strategy towards designing the surfaces of various oxides with graphene nanoheterostructures for high performance of energy-conversion devices.

Vascular anomalies encountered during pancreatoduodenectomy: do they influence outcomes?

BACKGROUND: Because of the potential risk of hemorrhage or ischemia, the presence of vascular anomalies adds to the surgical challenge in pancreatoduodenectomy (PD). OBJECTIVE: To analyze the literature concerning the influence of aberrant peripancreatic arterial anatomy on outcomes of PD. MATERIALS AND METHODS: A systematic search using Medline and Embase for the years 1950-2008. RESULTS: The most common aberration in hepatic arterial anatomy is the replaced right hepatic artery. Other vascular abnormalities such as replaced common hepatic artery with a hepatomesenteric trunk and celiomesenteric trunk and arcuate ligament syndrome leading to celiac artery stenosis are also associated with post-PD complications. Damage to the biliary branches of the hepatic arteries increases the risk of postoperative biliary anastomotic leak. CONCLUSION: The most common abnormalities of the hepatic vasculature include a replaced RHA, replaced LHA, and accessory RHA or LHA. Celiac artery stenosis secondary to median arcuate ligament compression may also be encountered. Every attempt should be made to preserve the aberrant vessel unless their resection is oncologically indicated. Routine preoperative computerized tomography angiography helps to identify the hepatic vascular anatomy and thereby prepares the surgeon to better deal with the vascular anomalies intraoperatively. Increased awareness of the vascular anatomy would decrease the chances of intraoperative vascular injury and consequent postoperative complications such as biliary anastomotic leaks as well as the chances of postoperative hemorrhage.

Psoas hematoma due to segmental vessel injury leads to paresis following CT-guided biopsy of lumbar vertebrae: A case report.

BACKGROUND: Percutaneous bone biopsy is the first-line procedure for obtaining a tissue diagnosis to confirm focal, diffuse vertebral, and/or paravertebral metastatic lesions. Percutaneous bone biopsy to evaluate metastatic disease can be performed under fluoroscopy, ultrasonography, magnetic resonance (MR) imaging, and computed tomography (CT). Notably, CT-scans best direct and demonstrate the needle position for these procedures, decreasing the risk of injury to critical adjacent structures (e.g. major vessels, nerve roots). Hemorrhagic complication to lumbar segmental arteries following needle biopsy are uncommon; only a few cases have been reported. Although percutaneous bone biopsy is typically safe when performed utilizing computed tomography (CT) guidance, here we encountered a 60-year-old-female who developed a L4 lumbar segmental artery psoas hematoma following this procedure requiring emergent embolization. CASE DESCRIPTION: A 60-year-old female, with a history of breast cancer, underwent a CT-guided core needle biopsy of an L4 lytic lesion (e.g., likely a metastasis). This acutely resulted in the onset of radicular leg pain and weakness. When the postprocedural CT scan demonstrated a large psoas hematoma attributed to laceration of the left posterior L4 segmental artery, the patient required emergent embolization. Following this procedure, she exhibited a fully neurological recovery. CONCLUSION: Following a CT-guided L4 vertebral biopsy to document metastatic breast carcinoma, a 60-year-old patient developed an immediate postprocedure CT-documented psoas hematoma due to laceration of the left posterior L4 segmental artery. Following emergent embolization, the patient recovered full neurological function.

Nanostructured N doped TiO2 efficient stable catalyst for Kabachnik-Fields reaction under microwave irradiation.

Herein, we report nitrogen-doped TiO2 (N-TiO2) solid-acid nanocatalysts with heterogeneous structure employed for the solvent-free synthesis of α-aminophosphonates through Kabachnik-Fields reaction. N-TiO2 were synthesized by direct amination using triethylamine as a source of nitrogen at low temperature and optimized by varying the volume ratios of TiCl4, methanol, water, and triethylamine, under identical conditions. An X-ray diffraction (XRD) study showed the formation of a rutile phase and the crystalline size is 10 nm. The nanostructural features of N-TiO2 were examined by HR-TEM analysis, which showed they had rod-like morphology with a diameter of ∼7 to 10 nm. Diffuse reflectance spectra show the extended absorbance in the visible region with a narrowing in the band gap of 2.85 eV, and the high resolution XPS spectrum of the N 1s region confirmed successful doping of N in the TiO2 lattice. More significantly, we found that as-synthesized N-TiO2 showed significantly higher catalytic activity than commercially available TiO2 for the synthesis of a novel series of α-amino phosphonates via Kabachnik-Fields reaction under microwave irradiation conditions. The improved catalytic activity is due to the presence of strong and Bronsted acid sites on a porous nanorod surface. This work signifies N-TiO2 is an efficient stable catalyst for the synthesis of α-aminophosphonate derivatives.

A hierarchical SnS@ZnIn2S4 marigold flower-like 2D nano-heterostructure as an efficient photocatalyst for sunlight-driven hydrogen generation.

Herein, we report the in situ single-step hydrothermal synthesis of hierarchical 2D SnS@ZnIn2S4 nano-heterostructures and the examination of their photocatalytic activity towards hydrogen generation from H2S and water under sunlight. The photoactive sulfides rationally integrate via strong electrostatic interactions between ZnIn2S4 and SnS with two-dimensional ultrathin subunits, i.e. nanopetals. The morphological study of nano-heterostructures revealed that the hierarchical marigold flower-like structure is self-assembled via the nanopetals of ZnIn2S4 with few layers of SnS nanopetals. Surprisingly, it also showed that the SnS nanopetals with a thickness of ∼25 nm couple in situ with the nanopetals of ZnIn2S4 with a thickness of ∼25 nm to form a marigold flower-like assembly with intimate contact. Considering the unique band gap (2.0-2.4 eV) of this SnS@ZnIn2S4, photocatalytic hydrogen generation from water and H2S was performed under sunlight. SnS@ZnIn2S4 exhibits enhanced hydrogen evolution, i.e. 650 µmol h-1 g-1 from water and 6429 µmol h-1 g-1 from H2S, which is much higher compared to that of pure ZnIn2S4 and SnS. More significantly, the enhancement in hydrogen generation is 1.6-2 times more for H2S splitting and 6 times more for water splitting. SnS@ZnIn2S4 forms type I band alignment, which accelerates charge separation during the surface reaction. Additionally, this has been provoked by the nanostructuring of the materials. Due to the nano-heterostructure with hierarchical morphology, the surface defects increased which ultimately suppresses the recombination of the electron-hole pair. The above-mentioned facts demonstrate a significant improvement in the interface electron transfer kinetics due to such a unique 2D nano-heterostructure semiconductor which is responsible for a higher photocatalytic activity.

Multidimensional management of a vascular injury following total knee arthroplasty: A rare case report.

Acute vascular injury during total knee arthroplasty (TKA) is an extremely rare complication, but one which can have devastating consequences threatening the limb and/or life of the patient if not diagnosed and managed at the earliest. The clinical presentation can vary from acute haemorrhage or ischemia in the peri operative period; to a delayed presentation of recurrent swelling and pain secondary to a geniculate or popliteal artery pseudoaneurysm. This is the first reported case of an acute inferolateral genicular artery haemorrhage following TKA and the associated medical complications. It was successfully managed with emergency percutaneous endovascular coiling and appropriate medical management. This case highlights that clinical suspicion, prompt diagnosis and urgent intervention with a multidisciplinary approach can help successfully manage a vascular insult.

Plasmonic Ag decorated CdMoO4 as an efficient photocatalyst for solar hydrogen production.

The synthesis of Ag-nanoparticle-decorated CdMoO4 and its photocatalytic activity towards hydrogen generation under sunlight has been demonstrated. The CdMoO4 samples were synthesized by a simple hydrothermal approach in which Ag nanoparticles were in situ decorated on the surface of CdMoO4. A morphological study showed that 5 nm spherical Ag nanoparticles were homogeneously distributed on the surface of CdMoO4 particles. The UV/DRS spectra show that the band gap of CdMoO4 was narrowed by the incorporation of a small amount of Ag nanoparticles. The surface plasmonic effect of Ag shows broad absorption in the visible region. The enhanced photocatalytic hydrogen production activities of all the samples were evaluated by using methanol as a sacrificial reagent in water under natural sunlight conditions. The results suggest that the rate of photocatalytic hydrogen production using CdMoO4 can be significantly improved by loading 2% Ag nanoparticles: i.e. 2465 µmol h-1 g-1 for a 15 mg catalyst. The strong excitation of surface plasmon resonance (SPR) absorption by the Ag nanoparticles was found in the Ag-loaded samples. In this system, the role of Ag nanoparticles on the surface of CdMoO4 has been discussed. In particular, the SPR effect is responsible for higher hydrogen evolution under natural sunlight because of broad absorption in the visible region. The current study could provide new insights for designing metal/semiconductor interface systems to harvest solar light for solar fuel generation.