Paraneoplastic Hypercholesterolemia Identified in an Adult Male Diagnosed With Metastatic Yolk Sac Tumor.

A few cases of paraneoplastic hypercholesterolemia have been reported in patients with primary or metastatic liver cancer. We report a case of paraneoplastic hypercholesterolemia in a patient with a metastatic yolk sack tumor. The patient was a 52-year-old man who presented with abdominal pain, nausea, and vomiting. A computed tomography (CT) scan demonstrated massive hepatomegaly with innumerable large ill-defined hypo-densities and innumerable pulmonary nodules. Blood work demonstrated elevated bilirubin to 3.1 mg/dL, aspartate aminotransferase (AST) to 384 U/L, alanine aminotransferase (ALT) to 126 U/L, gamma-glutamyl transferase (GGT) to 574 U/L, lipase to 100 U/L, low-density lipoprotein (LDL) of 579 mg/dL, and cholesterol of >800 mg/dL. Tumor markers revealed alpha-fetoprotein (AFP) was 24,760 ng/mL, carcinoembryonic antigen (CEA) was 1.9 ng/mL, and cancer antigen 19-9 (CA19-9) was 86 U/mL. The tumor makers were obtained during the initial stages of the patient's evaluation to help us narrow down the possible primary - focusing on the gastrointestinal tract and the pancreas. Although tumor markers are rarely of use in the early diagnosis of cancer due to their limited sensitivity and specificity; however, they can help diagnose the origin of cancer in patients presenting with advanced widespread disease such as our patient. Histopathology of his liver lesion biopsy demonstrated a metastatic yolk sac tumor (YST) with hepatoid differentiation. Since the patient succumbed rapidly, the primary tumor could not be ascertained, although the lack of a classic pattern for testicular tumor retroperitoneal lymphadenopathy makes extragonadal YST more likely. YSTs are major histologic subtypes of germ cell tumors (GCTs), and most frequently arise in the gonads. However, extragonadal GCT is sometimes seen and comprises about 2-5% of all GCTs in adult males aged 15-35 years. Extra gonadal GCT has been hypothesized to occur through aberrant migration of primordial germ cells or reverse migration of transformed germ cells from the testes, and persistence of pluripotent cells outside the gonads. Paraneoplastic syndromes associated with GCTs are rare. The pathophysiology of paraneoplastic hypercholesterolemia is hypothesized to involve the dysregulation of LDL receptors. Cancer-mediated mutations in the LDL receptor gene result in an abnormal LDL receptor, leading to autonomous cholesterol production by neoplastic cells. Also, tumor-secreted proprotein convertase subtilisin/kexin type 9 (PCSK9) has been implicated in the causation of paraneoplastic hypercholesterolemia. PCSK9 binds to and degrades the receptor for LDL particles on cell membranes. YST in adults is exceedingly rare. Paraneoplastic hypercholesterinemia is a very rare phenomenon reported in different cancers and we report the first case associated with YST.

Hollow Mesoporous Silica Nanoparticles for Dual Chemo-starvation Therapy of Hepatocellular Carcinoma.

PURPOSE: This study aims at chemotherapy and starvation therapy of HCC via starvation and apoptosis. METHODS: Hollow mesoporous organosilica nanoparticles (HMONs) with the thioether-hybrid structure were developed using an organic/inorganic co-templating assembly approach. Hydrofluoric acid was used to remove the internal MSN core for yielding large radial mesopores for loading drug cargos. The morphology and structure of NPs were determined using TEM and SEM. HMONs were stepwise surface modified with glucose oxidase (GOx), oxygen (O2) and Doxorubicin (DOX), and cancer cell membrane (CCM) for yielding CCM-coated HMONs (targeted stealth biorobots; TSBRs) for starvation, apoptotic, and enhanced cell uptake properties, respectively. The surface area and pore size distribution were determined via BET and BJH assays. The catalytic ability of GOx-modified NPs was measured using in vitro glucose conversion approach authenticated by H2O2 and pH determination assays. MTT assay was used to determine the cytotoxicities of NPs. Cell uptake and apoptotic assay were used for the NPs internalization and apoptosis mechanisms. The subcutaneous HepG2 tumor model was established in mice. The long-term in vivo toxicity was determined using blood assays. RESULTS: The prepared NPs were spherical, hollow and mesoporous with excellent surface area and pore size distribution. The GOx-modified NPs exhibited excellent catalytic activity. The TSBRs showed better cytotoxicity and reduce the tumor size and weight. The NPs showed long-term safety in vivo. CONCLUSION: TSBRs destroyed cancer cells by starvation and chemotherapy in both in-vitro and in-vivo settings which demonstrates its anti-cancer potential.

Generation of LexA enhancer-trap lines in Drosophila by an international scholastic network.

Conditional gene regulation in Drosophila through binary expression systems like the LexA-LexAop system provides a superb tool for investigating gene and tissue function. To increase the availability of defined LexA enhancer trap insertions, we present molecular, genetic, and tissue expression studies of 301 novel Stan-X LexA enhancer traps derived from mobilization of the index SX4 line. This includes insertions into distinct loci on the X, II, and III chromosomes that were not previously associated with enhancer traps or targeted LexA constructs, an insertion into ptc, and seventeen insertions into natural transposons. A subset of enhancer traps was expressed in CNS neurons known to produce and secrete insulin, an essential regulator of growth, development, and metabolism. Fly lines described here were generated and characterized through studies by students and teachers in an international network of genetics classes at public, independent high schools, and universities serving a diversity of students, including those underrepresented in science. Thus, a unique partnership between secondary schools and university-based programs has produced and characterized novel resources in Drosophila, establishing instructional paradigms devoted to unscripted experimental science.

Conical drill bit for optimized external ventricular drain placement: a proof-of-concept study.

OBJECTIVE: Despite external ventricular drain (EVD) procedures being commonplace in neurosurgical practice, suboptimal placement rates remain high, and complications are not uncommon. The angle of the EVD catheter insertion and the accuracy of the drill hole placement are major factors determining successful EVD placement that are dependent on the drill bit morphology. The standard cylindrical 2-fluted twist drill bit creates a relatively deep and narrow drill hole that requires precise positioning, has limited visibility of the drill hole bottom and restricted catheter angular adjustment range, and poses the risk of inadvertent dural puncture. To overcome the standard problems associated with EVD drill bit morphology, the authors propose novel cone-shaped drill bits for EVD placement. METHODS: Conical drill bits of 30° and 45° were designed, manufactured, and tested in a simulated laboratory setting as well as in three human cadavers with intact skull, dura mater, and brain. Drill bit performance was rated by neurosurgical trainees across various domains using Likert scale-type questions. RESULTS: In the laboratory, maximum drilling temperatures adjacent to the drill hole were recorded and compared for the standard drill bit and the 30° and 45° conical drill bits and were not significantly different (p = 0.631 and p = 0.326, respectively). The maximum temperature recorded directly underneath the drilling site for the 45° drill bit was significantly higher than the temperature of the standard drill bit (p = 0.043). The differences between the standard and 30° drill bits were not significant (p = 0.783). Upon cadaver testing, the drilling times with 30° and 45° conical drill bits were significantly longer than those with the standard drill bit (p = 0.036 and p = 0.002, respectively). Likert scale scores were significantly higher for the conical 30° (median [IQR] 4.7 [3.3-5]) and 45° (4 [2-5]) drill bits than for the standard drill bit (1.7 [1-2.5], p < 0.0001), indicating significantly better performance. Conical drill bits used as a "rescue" strategy allowed for an EVD catheter angular adjustment range 6 to 9 times greater than that for the standard drill bit and resulted in a zero inadvertent dural puncture rate. CONCLUSIONS: The 30° conical drill bit can be safely used on its own or as a rescue tool to potentially achieve improved confidence, visualization, targeting, and precision of EVD placement while essentially eliminating the possibility of unintentional dural puncture with minimal increase in the total procedure time.

Implementation of a comprehensive set of optimised CBCT protocols and validation through imaging quality and dose audit.

OBJECTIVES: Cone-beam computed tomography (CBCT) for radiotherapy treatment verification has increased in frequency; therefore, it is crucial to optimise image quality and radiation dose to patients. The aim of this study was to implement optimised CBCT protocols for the Varian TrueBeams for most tumour sites in adult patients. METHODS: A combination of patient size-specific CBCT protocols from the literature and developed in-house was used. Scans taken before and after optimisation were compared by senior radiographers and physicists to evaluate how changes affected image quality and clinical usability for online image registration. The change in dose for each new CBCT protocol was compared to the Varian default. A clinical audit was performed following implementation to evaluate the changes in imaging dose for all patients receiving a CBCT during that period. RESULTS: Ten CBCT protocols were introduced including head and neck and patient-size-specific thorax and pelvis/abdomen protocols. Scans from 102 patients with images before and after optimisation were assessed, none of the scans showed image quality changes compromising clinical usability and for some image quality was improved. Between November 2020 and June 2021, 1185 patients had CBCTs using the new protocols. The imaging dose was reduced for 52% of patients, remained the same for 37% and increased for 12%. CONCLUSIONS: This study showed that substantial dose reductions and image quality improvements can be achieved with simple changes in the default settings of the Varian TrueBeam CBCT without affecting the radiographers' confidence in online image registration. ADVANCES IN KNOWLEDGE: This study represents a comprehensive assessment and optimisation of CBCT protocols for most sites, validated on a large cohort of patients.

Occurrence, influencing factors, toxicity, regulations, and abatement approaches for disinfection by-products in chlorinated drinking water: A comprehensive review.

Disinfection is considered as a vital step to ensure the supply of clean and safe drinking water. Various approaches are adopted for this purpose; however, chlorination is highly preferred all over the world. This method is opted owing to its several advantages. However, it leads to the formation of certain by-products. These chlorination disinfection by-products (DBPs) are genotoxic, carcinogenic and mutagenic. Still chlorination is being practiced worldwide. Present review gives insights into the occurrence, toxicity and factors affecting the formation of regulated (THMs, HAAs) and emerging DBPs (N-DBPs, HKs, HAs and aromatic DBPs) found in drinking water. Furthermore, remediation techniques used to control DBPs have also been summarized here. Key findings are: (i) concentration of regulated DBPs surpassed the permissible limit in most of the regions, (ii) high chlorine dose, high NOM, more reaction time (up to 3 h) and high temperature (up to 30 °C) enhance the formation of THMs and HAAs, (iii) high pH favors the formation of THMs while low pH is suitable of the formation of HAAs, (iv) high NOM, low temperature, low chlorine dose and moderate pH favors the formation of unstable DBPs (N-DBPs, HKs and HAs), (v) DBPs are toxic not only for humans but for aquatic fauna as well, (vi) membrane technologies, enhanced coagulation and AOPs remove NOM, (vii) adsorption, air stripping and other physical and chemical methods are post-formation approaches (viii) step-wise chlorination is assumed to be an efficient method to reduce DBPs formation without any treatment. Toxicity data revealed that N-DBPs are found to be more toxic than C-DBPs and aromatic DBPs than aliphatic DBPs. In majority of the studies, merely THMs and HAAs have been studied and USEPA has regulated just these two groups. Future studies should focus on emerging DBPs and provide information regarding their regulation.

A systematic review of medicinal plants used against Echinococcus granulosus.

Cystic echinococcosis (CE) is a zoonotic helminthiasis caused by different species of the genus Echinococcus, and is a major economic and public health concern worldwide. Synthetic anthelmintics are most commonly used to control CE, however, prolonged use of these drugs may result in many adverse effects. This study aims to discuss the in vitro/in vivo scolicidal efficacy of different medicinal plants and their components used against Echinococcus granulosus. Google Scholar, ScienceDirect, PubMed and Scopus were used to retrieve the published literature from 2000-2020. A total of 62 published articles met the eligibility criteria and were reviewed. A total of 52 plant species belonging to 22 families have been reported to be evaluated as scolicidal agents against E. granulosus worldwide. Most extensively used medicinal plants against E. granulosus belong to the family Lamiaceae (25.0%) followed by Apiaceae (11.3%). Among various plant parts, leaves (36.0%) were most commonly used. Essential oils of Zataria multiflora and Ferula asafetida at a concentration of 0.02, and 0.06 mg/ml showed 100% in vitro scolicidal activity after 10 min post application, respectively. Z. multiflora also depicted high in vivo efficacy by decreasing weight and size while also causing extensive damage to the germinal layer of the cysts. Plant-based compounds like berberine, thymol, and thymoquinone have shown high efficacy against E. granulosus. These plant species and compounds could be potentially used for the development of an effective drug against E. granulosus, if further investigated for in vivo efficacy, toxicity, and mechanism of drug action in future research.