Clinical Presentation and Management of Malignant Psoas Syndrome: A Scoping Review of Case Reports and Case Series.

Malignant psoas syndrome (MPS) is a rare and underreported clinical syndrome that significantly impacts the quality of life of cancer patients through metastatic infiltration of the iliopsoas muscle. Patients suffering from MPS often present with painful hip flexion, loss of mobility, and immense pain in their legs and back. The current literature describing the clinical presentation, management, and prognosis of MPS is limited primarily to case reports and outdated literature reviews. There remains a gap in the current knowledge of MPS and in the management of this complex cancer-related pain syndrome. Thus, this scoping review aimed to map current case reports and case series on MPS for clinical presentation, treatment modalities, and resulting prognoses of MPS in late-stage cancer patients. A systemized search using the databases Embase and PubMed (Medline) was conducted to access case reports and case series published between January 1990 and October 2022 that met the study's inclusion criteria: (1) adult patients with metastatic cancer; (2) MPS symptoms secondary to infiltration of iliopsoas; (3) clinical presentation, treatment modality, and prognosis; and (4) English-language text. Our search strategy yielded 1926 citations. After removing 629 duplicates, 1,283 reports were excluded due to failure to meet eligibility criteria (n=1,271) or inaccessibility (n=12). Using the JBI appraisal tools for case reports and case series, a total of 14 articles remained for the final review. With histories of either genitourinary, hepatic, gastric, or skin cancer, each case reported new onset intense pain in the legs, back, abdomen, or pelvis with associated symptoms such as flexion of the hip or gait disorder. A computerized tomography (CT) scan, magnetic resonance imaging (MRI), or positron emission tomography (PET) scan typically confirmed metastasis into the iliopsoas causing these symptoms, which suggested MPS. Each case utilized two to seven different pain management strategies to alleviate MPS symptoms. Many cases first used opioids for pain relief. Following a necessitated increase in morphine equivalent daily dose, a subsequent increase in the strength of analgesic, change in route of administration, and integration of combination drug therapy were generally added to the treatment regime. Many cases reported successful management of symptoms through utilizing methadone, radiation therapy, botulinum toxin injection, increased opioid dosage, or epidural catheter administration of opioids. A unified clinical definition of MPS may be required to inform physicians of this syndrome to help support clinical decisions regarding treatments for patients. The studies indicated that a clearer guideline for treatment protocol may be warranted as most cases reported utilizing various treatment medication dosages and procedures with vastly differing results.

The protective effect of pneumococcal vaccination on cardiovascular disease in adults: A systematic review and meta-analysis.

BACKGROUND: Epidemiological studies suggest that there is a link between pneumococcal infection and adverse cardiovascular outcomes such as myocardial infarction. Multiple studies have evaluated the protective effect of the 23-valent polysaccharide pneumococcal vaccination (PPV23), but results have varied. Therefore, a meta-analysis was conducted to summarize available evidence on the impact of PPV23 on cardiovascular disease. METHODS: A literature search from January 1946 to September 2019 was conducted across Embase, Medline and Cochrane. All studies were included that evaluated PPV23 compared with a control (placebo, no vaccine or another vaccine) for any cardiovascular events, including: myocardial infarction (MI), heart failure and cerebrovascular events. Risk ratios (RRs) were pooled using random effects models. RESULTS: Eighteen studies were included, with a total of 716,108 participants. Vaccination with PPV23 was associated with decreased risk of any cardiovascular event (RR: 0.91; 95% CI: 0.84-0.99), and MI (RR: 0.88; 95% CI: 0.79-0.98) in all age groups, with a significant effect in those aged ≥65 years, but not in the younger age group. Similarly, PPV23 vaccine was associated with significant risk reduction in all-cause mortality in all ages (RR: 0.78; 95% CI: 0.68-0.88), specifically in those aged ≥65 years (RR: 0.71; 95% CI: 0.60-0.84). A significant risk reduction in cerebrovascular disease was not observed following pneumococcal vaccination. CONCLUSIONS: Polysaccharide pneumococcal vaccination decreased the risk for some adverse cardiovascular events, specifically acute MI in the vaccinated population, particularly for those individuals aged ≥65 years. It would be highly beneficial to vaccinate the population who is at greater risk of cardiovascular diseases.

RhoA/ROCK pathway inhibitor ameliorates erectile dysfunction induced by radiation therapy in rats.

OBJECTIVES: Prostate cancer (PCa) treatment with radiation therapy (RT) has an excellent cure rate. However, Radiation-induced Erectile Dysfunction (RiED) is a common and irreversible toxicity impacting quality of life, and there is no FDA approved specific drug for RiED. We previously showed that prostate RT increased RhoA/ROCK signaling in the cavernous nerve (CN) and penile tissues, which may lead to RiED in rats. In this study, we investigated whether RhoA/ROCK pathway inhibition by a specific inhibitor called Hydroxyfasudil (HF) can improve RiED in our well-established rat model. MATERIALS/METHODS: Male Sprague-Dawley rats were randomized to the following groups: sham-RT, HF-only, RT-only, and RT + HF. Rats were either exposed to a single dose of 25 Gy prostate-confined RT or a sham procedure. 10 mg/kg HF or normal saline was injected intraperitoneally. Erectile function was evaluated by intracavernosal pressure (ICP) and mean arterial pressure (MAP) measurements at week 14 post-RT. Cavernous nerve (CN) injury was evaluated by transmission electron microscopy (TEM), and penile tissue fibrosis by Masson trichrome staining (MT). RESULTS: We have found that the HF treatment prior to RT showed significant (p < 0.001) improvement in ICP/MAP ratio, area under the curve, and maximum ICP value, compared to RT-alone rats. Furthermore, RT + HF treated rats exhibited increased CN myelination and decreased axonal atrophy, comparted to RT-only. HF treatment showed significantly decreased penile tissue fibrosis (p < 0.05) compared to RT-alone treated rats. CONCLUSION: Our results provide the first preclinical evidence that targeting RhoA/ROCK pathway by HF may provide a novel therapeutic option for the treatment of RiED.

Regulation of RhoB Gene Expression during Tumorigenesis and Aging Process and Its Potential Applications in These Processes.

RhoB, a member of the Ras homolog gene family and GTPase, regulates intracellular signaling pathways by interfacing with epidermal growth factor receptor (EGFR), Ras, and phosphatidylinositol 3-kinase (PI3K)/Akt to modulate responses in cellular structure and function. Notably, the EGFR, Ras, and PI3K/Akt pathways can lead to downregulation of RhoB, while simultaneously being associated with an increased propensity for tumorigenesis. Functionally, RhoB, part of the Rho GTPase family, regulates intracellular signaling pathways by interfacing with EGFR, RAS, and PI3K/Akt/mammalian target of rapamycin (mTOR), and MYC pathways to modulate responses in cellular structure and function. Notably, the EGFR, Ras, and PI3K/Akt pathways can lead to downregulation of RhoB, while simultaneously being associated with an increased propensity for tumorigenesis. RHOB expression has a complex regulatory backdrop consisting of multiple histone deacetyltransferase (HDACs 1 and 6) and microRNA (miR-19a, -21, and -223)-mediated mechanisms of modifying expression. The interwoven nature of RhoB's regulatory impact and cellular roles in regulating intracellular vesicle trafficking, cell motion, and the cell cycle lays the foundation for analyzing the link between loss of RhoB and tumorigenesis within the context of age-related decline in RhoB. RhoB appears to play a tissue-specific role in tumorigenesis, as such, uncovering and appreciating the potential for restoration of RHOB expression as a mechanism for cancer prevention or therapeutics serves as a practical application. An in-depth assessment of RhoB will serve as a springboard for investigating and characterizing this key component of numerous intracellular messaging and regulatory pathways that may hold the connection between aging and tumorigenesis.

Tuning the Metal/Chalcogen Composition in Copper(I)-Chalcogenide Clusters with Cyclic (Alkyl)(amino)carbene Ligands.

A series of phosphorescent homo- and heterometallic copper(I)-chalcogenide clusters stabilized by cyclic (alkyl)(amino)carbene ligands [Cu4M4(µ3-E)4(CAACCy)4] (M = Cu, Ag, Au; E = S, Se) has been synthesized by the reaction of the new copper(I) trimethylsilylchalcogenolate compounds [(CAACCy)CuESiMe3] with ligand-supported group 11 acetates. The clusters are emissive at 77 K in solution and the solid state, with emission colors that depend on the metal/chalcogen composition. Electronic structure calculations point to a common 3[(M++E2-)LCT] emissive state for the series.

Exploring function activated chlorins using MCD spectroscopy and DFT methods: design of a chlorin with a remarkably intense, red Q band.

The electronic structures of three previously synthesized Ni-coordinated chlorins with ß-substituents of thioketone, fluorene, and ketone were investigated using magnetic circular dichroism spectroscopy (MCD) and density functional theory (DFT) for potential application as sensitizers for dye-sensitized solar cells (DSSCs). Computational studies on modeled Zn-coordinated chlorins allowed identification of charge transfer and d-d transitions of the Ni2+ coordinated chlorins. Two fictive Zn chlorins, M1 and M2, were designed with thiophene units based on the fluorene substituted chlorin. Substitution with thiophene altered the typical arrangement of the four Gouterman molecular orbitals (MOs) and red-shifted and greatly intensified the lowest energy absorption band (the Q band). The introduction of the thiophene-based MO as the LUMO below the usual Gouterman LUMO is predicted to increase the efficiency of electron transfer from the dye to the conduction band of the semiconductor in DSSCs. The addition of a donor group on the opposite pyrrole (M2) red-shifted the Q band further and introduced a donor-based MO between the typical Gouterman HOMO and HOMO-1. Despite the relatively small ΔHOMO, M1 and M2 exhibited remarkably intense Q bands. M2 would be a possible candidate for application in DSSCs due to its panchromatic absorption, intense and red-shifted Q band, and the presence of the substituent based MO properties. Another indicator of a successful dye is the alignment of the ground state and excited state oxidation potentials (GSOP and ESOP, respectively) with respect to the conduction band of the semiconductor. The GSOP for M2 lies 0.55 eV below the I-/I3- redox potential and the ESOP lies 0.48 eV above the TiO2 conduction band. The impact of the thiophene dominance in the LUMO also supports the prediction of efficient sensitization properties. The remarkably intense Q band of M2 predicted to be at 777 nm with a ΔHOMO of just 1.04 eV provides a synthetic route to tetrapyrroles with extremely intense, red Q bands without the need for aza nitrogens of the phthalocyanines. This study illustrates the value of guided synthesis using MCD spectral analysis and computational methods for optimizing the design of porphyrin dyes.

The spectroscopic impact of interactions with the four Gouterman orbitals from peripheral decoration of porphyrins with simple electron withdrawing and donating groups.

Tetrapyrroles are of great interest for solar cell and photodynamic therapy applications due to their structural analogy with chlorophyll, a natural photosensitizer. Unsubstituted symmetric porphyrins exhibit weak absorption in the red region which makes them unsuitable for these applications. The push-pull peripheral decoration modifies the energies of the frontier molecular orbitals, which in turn influences the tetrapyrrole's spectroscopic properties. The absorption, magnetic circular dichroism, and emission spectra were measured for four zinc tetratolylporphyrin compounds substituted peripherally with a fused dimethoxybenzo group as an electron withdrawing group (EWG) on one pyrrole and on the opposite pyrrole, a single acetamido (1), a nitro (2), a proton (3), or a benzoylamino (4) substituent. Unusually, the magnetic circular dichroism spectrum of 2 exhibited a negative A term for the lowest energy absorption band (the Q band) and its emission spectrum was also unlike those of 1, 3, and 4. A complete computational analysis was carried out to obtain the energies and electron distribution, shown by electron density surfaces, of the four Gouterman MOs. TD-DFT calculations showed that for 2, ΔLUMO was greater than ΔHOMO, which accounted for the observed negative A term. The trend in the estimated MCD A term magnitudes, normalized to the absorbance as [A/(dipole strength) BM], provides experimental confirmation of the computationally determined ratio of ΔLUMO/ΔHOMO data. The value of ΔHOMO was confirmed by the trend in oscillator strengths. A series of fictive porphyrins (F1-F5) incorporating simple push-pull substituents were designed and their electronic structures were investigated using TD-DFT calculations. The substituents in the five fictive molecules illustrate the differential effect of the donor and acceptor groups in the ß-position of the pyrroles on the relative stabilities of the four Gouterman orbitals. NO2 groups result in the greatest splitting of the LUMO pair. We show that on using strong EWGs, opposite electron donating groups result in a ΔLUMO > 0, which red-shifts the Q band and introduces a strong dipole. With the nitro and formyl EWGs, ΔLUMO becomes greater than ΔHOMO, resulting in a complex electronic structure of the Q band, recognizable by a negative A term suggesting a design objective for future photosensitizers.

A N-Heterocyclic Carbene-Stabilized Coinage Metal-Chalcogenide Framework with Tunable Optical Properties.

A new class of coinage-metal chalcogenide compounds [Au4M4(µ3-E)4(IPr)4] (M = Ag, Au; E = S, Se, Te) has been synthesized from the combination of N-heterocyclic carbene-ligated gold(I) trimethylsilylchalcogenolates [(IPr)AuESiMe3] and ligand-supported metal acetates. Phosphorescence is observed from these clusters in glassy 2-methyltetrahydrofuran and in the solid state at 77 K, with emission energies that depend on the selection of metal/chalcogen ion composition. The ability to tune the emission is attributed to electronic transitions of mixed ligand-to-metal-metal-charge-transfer (IPr → AuM2) and interligand (IPr → E) phosphorescence character, as revealed by time-dependent density functional theory computations.N-heterocyclic carbenes (NHCs) have been applied as ancillary ligands in the synthesis of luminescent gold(I) chalcogenide clusters and this approach allows for unprecedented selectivity over the metal and chalcogen ions present within a stable octanuclear framework.

Face identity recognition in simulated prosthetic vision is poorer than previously reported and can be improved by caricaturing.

The visual prosthesis (or "bionic eye") has become a reality but provides a low resolution view of the world. Simulating prosthetic vision in normal-vision observers, previous studies report good face recognition ability using tasks that allow recognition to be achieved on the basis of information that survives low resolution well, including basic category (sex, age) and extra-face information (hairstyle, glasses). Here, we test within-category individuation for face-only information (e.g., distinguishing between multiple Caucasian young men with hair covered). Under these conditions, recognition was poor (although above chance) even for a simulated 40×40 array with all phosphene elements assumed functional, a resolution above the upper end of current-generation prosthetic implants. This indicates that a significant challenge is to develop methods to improve face identity recognition. Inspired by "bionic ear" improvements achieved by altering signal input to match high-level perceptual (speech) requirements, we test a high-level perceptual enhancement of face images, namely face caricaturing (exaggerating identity information away from an average face). Results show caricaturing improved identity recognition in memory and/or perception (degree by which two faces look dissimilar) down to a resolution of 32×32 with 30% phosphene dropout. Findings imply caricaturing may offer benefits for patients at resolutions realistic for some current-generation or in-development implants.

Glutathione binding to dirhodium tetraacetate: a spectroscopic, mass spectral and computational study of an anti-tumour compound.

Glutathione (γ-l-glutamyl-l-cysteinyl-glycine) is a ubiquitous tripeptide found in all plants and animals. Glutathione has key roles as a metallochaperone and as a cellular thiol involved in metabolism. Little is known about how glutathione interacts with organometallic compounds in vivo. Here, we report the reactions of glutathione in vitro with dirhodium(ii) tetraacetate (tetrakis(µ-acetato)dirhodium(ii), Rh2(OAc)4), a compound with anti-tumour properties. Electrospray ionization mass spectrometry, UV-Visible absorption and circular dichroism spectroscopic methods were used to determine the stoichiometries and optical properties of the final conjugate. Computational analyses were used to predict the binding modes of glutathione to the Rh2(OAc)4, and report on the orbital assignments for the resulting products. We explored the competition by GSH for methionine-bound axial sites on Rh2(OAc)4 to investigate the use of weak thioether to protect its cellular-based anti-cancer activity. Our study highlights the important role that axial ligation would play in deactivating or significantly decreasing the efficacy of this bimetallic anti-tumor drug. The computational data explain the stability of the mono-adduct and the appearance of new absorption bands in the UV region including retention of the Rh-Rh single bond. Additionally, these data show that glutathione can effectively disable the potency of these metallo-drugs through orbital overlap of the entire Rh-Rh core as a result of the strong binding. Electronic absorption spectroscopy, mass spectrometry and computational analysis are a powerful combination in understanding possible chemical reactions in vivo and this information can be used to synthetically tune dirhodium complexes for use in the fight against cancer.

Insights from the genome of a high alkaline cellulase producing Aspergillus fumigatus strain obtained from Peruvian Amazon rainforest.

Here, we report the complete genome sequence of a high alkaline cellulase producing Aspergillus fumigatus strain LMB-35Aa isolated from soil of Peruvian Amazon rainforest. The genome is ∼27.5mb in size, comprises of 228 scaffolds with an average GC content of 50%, and is predicted to contain a total of 8660 protein-coding genes. Of which, 6156 are with known function; it codes for 607 putative CAZymes families potentially involved in carbohydrate metabolism. Several important cellulose degrading genes, such as endoglucanase A, endoglucanase B, endoglucanase D and beta-glucosidase, are also identified. The genome of A. fumigatus strain LMB-35Aa represents the first whole sequenced genome of non-clinical, high cellulase producing A. fumigatus strain isolated from forest soil.

Pathophysiological mechanisms underlying phenotypic differences in pulmonary radioresponse.

Differences in the pathogenesis of radiation-induced lung injury among murine strains offer a unique opportunity to elucidate the molecular mechanisms driving the divergence in tissue response from repair and recovery to organ failure. Here, we utilized two well-characterized murine models of radiation pneumonitis/fibrosis to compare and contrast differential gene expression in lungs 24 hours after exposure to a single dose of whole thorax lung irradiation sufficient to cause minor to major morbidity/mortality. Expression of 805 genes was altered as a general response to radiation; 42 genes were identified whose expression corresponded to the threshold for lethality. Three genes were discovered whose expression was altered within the lethal, but not the sublethal, dose range. Time-course analysis of the protein product of the most promising gene, resistin-like molecule alpha, demonstrated a significant difference in expression between radiosensitive versus radiotolerant strains, suggesting a unique role for this protein in acute lung injury.

Low-Symmetry Ω-Shaped Zinc Phthalocyanine Sensitizers with Panchromatic Light-Harvesting Properties for Dye-Sensitized Solar Cells.

Two low-symmetry phthalocyanines (Pcs) substituted with thiophene units at the non-peripheral (α) and peripheral (ß) positions were synthesized and their optical, electronic-structure, and electrochemical properties were investigated. The substitution of thiophene units at the α positions of the phthalocyanine skeleton resulted in a red shift of the Q band and significantly modified the molecular-orbital electronic distributions just below the HOMO and just above the LUMO, with distortion of the typical Gouterman four-orbital arrangement of MOs. Two amphiphilic Ω-shaped ZnPcs (αPcS1 and αPcS2) bearing a π-conjugated side chain with an adsorption site at an α position of the Pc macrocycle were synthesized as sensitizers for dye-sensitized solar cells (DSSCs). The absorption spectra of αPcS1 and αPcS2 showed red shifted Q bands and a broad band from 350 to 550 nm assignable to the intramolecular charge-transfer transition from the ZnPc core to the side chains. Time-dependent DFT calculations provided a clear interpretation of the effect of the thiophene conjugation on the typical phthalocyanine core π MOs. Compound αPcS1 was used as a light-harvesting dye on a TiO2 electrode for a DSSC, which showed a panchromatic response in the range 400-800 nm with a power conversion efficiency of 5.5 % under one-sun conditions.

Hypo-CpG methylation controls PTEN expression and cell apoptosis in irradiated lung.

PURPOSE: The current study was designed to address our hypothesis that oxidative stress secondary to the ionizing event upregulates phosphatase and tensin homolog (PTEN) mRNA and protein in the lungs of C57BL/6J mice through oxidative DNA damage resulting in CpG hypomethylation in the PTEN promoter. METHODS: Fibrosis-prone C57BL/6J mice were exposed to 0 or 15 Gy of 320 kVp X-rays to the whole thorax. Lung tissue was serially harvested at time points between one day and six months postirradiation. Tissue levels of PTEN mRNA, total protein, and phosphorylated PTEN, as well as CpG methylation of the PTEN promoter, expression of DNA methyltransferases 1 (Dnmt1) and 3a (Dnmt3a), NADPH oxidase 4 (Nox4) protein expression, and DNA damage levels were measured. The induction of DNA damage and global methylation changes were also examined in hydrogen peroxide (H2O2)-treated human umbilical vein endothelial cells (HUVECs) and human bronchial epithelial cells in vitro. RESULTS: These experiments demonstrate that PTEN mRNA and protein, Nox4 protein, and DNA damage levels increase continuously from one day to six months following radiation exposure. Elevated PTEN transcription and translation are likely the result of the observed decrease in CpG methylation of the PTEN promoter region. This finding is not consistent with the observed increase in Dnmt1 and Dnmt3a protein expression, implicating an alternative mechanism as the driving force behind hypomethylation. In vitro results provide evidence that H2O2 can induce DNA damage and affect DNA methylation status. The Mn porphyrin-based superoxide dismutase (SOD) mimic MnTnHEx-2-PyP(5+ )exhibited partial rescue from radiation-induced hypomethylation. CONCLUSIONS: Taken together, these data suggest that reactive oxygen species (ROS)-induced DNA damage results in hypomethylation of the PTEN promoter, upregulation of PTEN mRNA and protein, and a subsequent increase in apoptosis in irradiated lung tissue.