Value of Thallium-201 SPECT and SPECT/CT Brain Imaging in Differentiating Malignant From Nonmalignant Lesions: A Comparative Case-Series Study With Pathologic and/or Clinical Correlation.

BACKGROUND: Thallium-201 single-photon emission computed tomography/computed tomography (SPECT/CT) brain scan is an imaging modality which can be done to differentiate between malignant and nonmalignant lesions among patients with nonconclusive findings on conventional neuroimaging. This study describes the results of thallium-201 SPECT/CT brain imaging and relate it to histopathologic and/or clinical findings and evaluate the value of thallium-201 SPECT/CT brain imaging in differentiating malignant from nonmalignant lesions. METHODS: This is a retrospective case series study of 10 patients with cerebral lesions who underwent thallium-201 SPECT/CT brain imaging in a hospital in the Philippines from 2010 to 2021. RESULTS: A total of 10 patients underwent thallium-201 SPECT/CT brain scan. Six had negative results while 4 had positive results. All of the patients who had positive results were found to have malignancy, whether recurrent or newly diagnosed. All of the patients with negative scan were found to have either an infectious and inflammatory disease and responded to treatment albeit in different degrees. Two of the 10 patients underwent biopsy whose results were consistent with the thallium-201 SPECT/CT brain scan results. CONCLUSION: Thallium-201 brain scan combined with SPECT and SPECT/CT has been demonstrated to be useful in distinguishing malignant from nonmalignant lesions and is more cost-effective versus other imaging techniques. The findings in this study support the role of thallium scintigraphy in the diagnosis of patients with brain lesions most significantly when there is a need to differentiate between a malignant and benign condition.

Phenotyping the virulence of SARS-CoV-2 variants in hamsters by digital pathology and machine learning.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to evolve throughout the coronavirus disease-19 (COVID-19) pandemic, giving rise to multiple variants of concern (VOCs) with different biological properties. As the pandemic progresses, it will be essential to test in near real time the potential of any new emerging variant to cause severe disease. BA.1 (Omicron) was shown to be attenuated compared to the previous VOCs like Delta, but it is possible that newly emerging variants may regain a virulent phenotype. Hamsters have been proven to be an exceedingly good model for SARS-CoV-2 pathogenesis. Here, we aimed to develop robust quantitative pipelines to assess the virulence of SARS-CoV-2 variants in hamsters. We used various approaches including RNAseq, RNA in situ hybridization, immunohistochemistry, and digital pathology, including software assisted whole section imaging and downstream automatic analyses enhanced by machine learning, to develop methods to assess and quantify virus-induced pulmonary lesions in an unbiased manner. Initially, we used Delta and Omicron to develop our experimental pipelines. We then assessed the virulence of recent Omicron sub-lineages including BA.5, XBB, BQ.1.18, BA.2, BA.2.75 and EG.5.1. We show that in experimentally infected hamsters, accurate quantification of alveolar epithelial hyperplasia and macrophage infiltrates represent robust markers for assessing the extent of virus-induced pulmonary pathology, and hence virus virulence. In addition, using these pipelines, we could reveal how some Omicron sub-lineages (e.g., BA.2.75 and EG.5.1) have regained virulence compared to the original BA.1. Finally, to maximise the utility of the digital pathology pipelines reported in our study, we developed an online repository containing representative whole organ histopathology sections that can be visualised at variable magnifications (https://covid-atlas.cvr.gla.ac.uk). Overall, this pipeline can provide unbiased and invaluable data for rapidly assessing newly emerging variants and their potential to cause severe disease.

The Effectiveness of Ionized Water as a Radiodecontaminant for 99mTc-Pertechnetate and 131I.

Immediate and complete decontamination procedures are essential to restore the functionality, precision, accuracy, and safety of tests done within the nuclear medicine facility. Decontamination is a simple procedure that, if performed correctly, effectively reduces exposure brought about by spills. The determination of a suitable radiodecontaminant may be beneficial in decontaminating patient beds, collimators, probes, and machines. Methods: Two surface types (i.e., stainless steel and vinyl) were contaminated with a predetermined activity of 99mTcO4 and 131I. After air drying, static images of the contaminated surfaces were obtained using a γ-camera to determine the activity counts on each surface before and after decontamination procedures. Different decontaminant contact times (i.e., 5, 10, and 15 min) were used for each decontaminant (i.e., ionized water, 10% bleach, detergent solution, a negative control [no treatment], and a positive control [a commercial radiodecontaminant]). Differences between the effectiveness of ionized water and the other decontaminants against 99mTcO4 and 131I at different contact times were measured, and the mean percentage activity removed (%AR) was compared using 2-way ANOVA at the 0.05 level of significance. Results: 99mTcO4 and 131I contaminants had %ARs of greater than 80% after 5 min of contact time for ionized water and the other decontaminants. At 15 min contact time, ionized water was not as effective as the other decontaminating agents for 131I on vinyl surfaces. There was no significant interaction between the effects of the decontaminants (%AR) and the contact times with stainless steel and vinyl for either 99mTcO4 or 131I. Conclusion: For 99mTcO4 and 131I on stainless steel surfaces, ionized water is an effective decontaminant at contact times of 5, 10, and 15 min. For 99mTcO4 on vinyl surfaces, ionized water is also an effective decontaminant at contact times of 5, 10, and 15 min. For 131I on vinyl surfaces, ionized water is as effective as 10% bleach, detergent solution, and a commercial radiodecontaminant at contact times of 5 and 10 min.

Adeno-associated virus 2 infection in children with non-A-E hepatitis.

An outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland1 in April 2022 and has now been identified in 35 countries2. Several recent studies have suggested an association with human adenovirus with this outbreak, a virus not commonly associated with hepatitis. Here we report a detailed case-control investigation and find an association between adeno-associated virus 2 (AAV2) infection and host genetics in disease susceptibility. Using next-generation sequencing, PCR with reverse transcription, serology and in situ hybridization, we detected recent infection with AAV2 in plasma and liver samples in 26 out of 32 (81%) cases of hepatitis compared with 5 out of 74 (7%) of samples from unaffected individuals. Furthermore, AAV2 was detected within ballooned hepatocytes alongside a prominent T cell infiltrate in liver biopsy samples. In keeping with a CD4+ T-cell-mediated immune pathology, the human leukocyte antigen (HLA) class II HLA-DRB1*04:01 allele was identified in 25 out of 27 cases (93%) compared with a background frequency of 10 out of 64 (16%; P = 5.49 × 10-12). In summary, we report an outbreak of acute paediatric hepatitis associated with AAV2 infection (most likely acquired as a co-infection with human adenovirus that is usually required as a 'helper virus' to support AAV2 replication) and disease susceptibility related to HLA class II status.

Value of Thallium-201 SPECT and SPECT/CT Brain Imaging in Differentiating Malignant From Nonmalignant Lesions: A Comparative Case-Series Study With Pathologic and/or Clinical Correlation

Background@#Thallium-201 single-photon emission computed tomography/computed tomography(SPECT/CT) brain scan is an imaging modality which can be done to differentiate between malignant and nonmalignant lesions among patients with nonconclusive findings on conventional neuroimaging. This study describes the results of thallium-201 SPECT/CT brain imaging and relate it to histopathologic and/or clinical findings and evaluate the value of thallium-201 SPECT/CT brain imaging in differentiating malignant from nonmalignant lesions. @*Methods@#This is a retrospective case series study of 10 patients with cerebral lesions who un-derwent thallium-201 SPECT/CT brain imaging in a hospital in the Philippines from 2010 to 2021. @*Results@#A total of 10 patients underwent thallium-201 SPECT/CT brain scan. Six had nega-tive results while 4 had positive results. All of the patients who had positive results were found to have malignancy, whether recurrent or newly diagnosed. All of the patients with negative scan were found to have either an infectious and inflammatory disease and responded to treatment albeit in different degrees. Two of the 10 patients underwent biopsy whose results were consistent with the thallium-201 SPECT/CT brain scan results. @*Conclusion@#Thallium-201 brain scan combined with SPECT and SPECT/CT has been demon-strated to be useful in distinguishing malignant from nonmalignant lesions and is more cost-effective versus other imaging techniques. The findings in this study support the role of thallium scintigraphy in the diagnosis of patients with brain lesions most significantly when there is a need to differentiate between a malignant and benign condition.

Elevated temperature inhibits SARS-CoV-2 replication in respiratory epithelium independently of IFN-mediated innate immune defenses.

The pandemic spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of Coronavirus Disease 2019 (COVID-19), represents an ongoing international health crisis. A key symptom of SARS-CoV-2 infection is the onset of fever, with a hyperthermic temperature range of 38 to 41°C. Fever is an evolutionarily conserved host response to microbial infection that can influence the outcome of viral pathogenicity and regulation of host innate and adaptive immune responses. However, it remains to be determined what effect elevated temperature has on SARS-CoV-2 replication. Utilizing a three-dimensional (3D) air-liquid interface (ALI) model that closely mimics the natural tissue physiology of SARS-CoV-2 infection in the respiratory airway, we identify tissue temperature to play an important role in the regulation of SARS-CoV-2 infection. Respiratory tissue incubated at 40°C remained permissive to SARS-CoV-2 entry but refractory to viral transcription, leading to significantly reduced levels of viral RNA replication and apical shedding of infectious virus. We identify tissue temperature to play an important role in the differential regulation of epithelial host responses to SARS-CoV-2 infection that impact upon multiple pathways, including intracellular immune regulation, without disruption to general transcription or epithelium integrity. We present the first evidence that febrile temperatures associated with COVID-19 inhibit SARS-CoV-2 replication in respiratory epithelia. Our data identify an important role for tissue temperature in the epithelial restriction of SARS-CoV-2 independently of canonical interferon (IFN)-mediated antiviral immune defenses.

A prenylated dsRNA sensor protects against severe COVID-19.

Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severity. To better understand the antiviral defenses relevant to COVID-19, we used interferon-stimulated gene (ISG) expression screening to reveal that 2'-5'-oligoadenylate synthetase 1 (OAS1), through ribonuclease L, potently inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We show that a common splice-acceptor single-nucleotide polymorphism (Rs10774671) governs whether patients express prenylated OAS1 isoforms that are membrane-associated and sense-specific regions of SARS-CoV-2 RNAs or if they only express cytosolic, nonprenylated OAS1 that does not efficiently detect SARS-CoV-2. In hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting that this antiviral defense is a major component of a protective antiviral response.

Association of Asthma Diagnosis and Medication Use with Fecundability: A Prospective Cohort Study.

PURPOSE: Asthma has been positively associated with irregular menses and infertility in some studies, but data are limited on the relation between asthma medication use and fecundability (i.e., average per-cycle probability of conception among non-contracepting couples). This study examines the extent to which a history of asthma, asthma medication use, and age at first asthma diagnosis are associated with fecundability among female pregnancy planners. PARTICIPANTS AND METHODS: Pregnancy Study Online (PRESTO) is an ongoing, web-based preconception cohort study of couples aged 21-45 years from North America. Between July 2013 and July 2019, a total of 10,436 participants enrolled in PRESTO, and 8286 were included in the present analysis. At study enrollment, women reported whether they had ever been diagnosed with asthma and, if so, the year they were first diagnosed. Women who reported ever being diagnosed with asthma were asked about medication use, including medication type and frequency of use. Participants completed follow-up questionnaires every 8 weeks for up to 12 months or until pregnancy. Proportional probabilities regression models were used to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), adjusting for potential confounders. Fecundability ratios below 1.00 indicate reduced probability of conception. RESULTS: There was little association between a history of asthma diagnosis or asthma medication use and fecundability. Compared with no history of asthma, the FR for ever-diagnosis of asthma with medication use was 1.02 (95% CI: 0.91-1.15) and for ever-diagnosis of asthma without medication use was 1.00 (95% CI: 0.91-1.09). Highest intensity asthma medication use (daily plus extra dosing for symptoms), combination inhaled corticosteroid and long-acting beta-agonist inhaler use, and a first diagnosis of asthma after age 17 years were associated with small reductions in fecundability. CONCLUSION: The present study provides little evidence that asthma or asthma medication use is adversely associated with fecundability.

Crystal structure of di-methyl-formamidium bis-(tri-fluoro-methane-sulfon-yl)amide: an ionic liquid.

At 100 K, the title mol-ecular salt, C3H8NO+·C2F6NO4S2-, has ortho-rhom-bic (P212121) symmetry; the amino H atom of bis-(tri-fluoro-methane-sulfon-yl)amine (HNTf2) was transferred to the basic O atom of di-methyl-formamide (DMF) when the ionic liquid components were mixed. The structure displays an O-H⋯N hydrogen bond, which links the cation to the anion, which is reinforced by a non-conventional C-H⋯O inter-action, generating an R22(7) loop. A further very weak C-H⋯O inter-action generates an [001] chain.

A Frustrated and Confused Lewis Pair.

We report a new class of frustrated Lewis pairs (FLPs) by the hydroboration of bulky isocyanates iPr2 ArNCO (iPr2 Ar=2,6-iPr2 C6 H3 ) and Ph2tBu ArNCO (Ph2tBu Ar=2,6-Ph2 -4-tBuC6 H2 ) with Piers' borane (HB(C6 F5 )2 ). While hydroboration of smaller isocyanates such as iPr2 ArNCO leads to isocyanate-N/B FLP adducts, hydroboration of the bulkier Ph2tBu ArNCO allows isolation of the substrate-free aminoborane with a short, covalent N-B bond. This confused FLP reversibly binds unsaturated substrates such as isocyanates and isocyanides, suggesting the intermediacy of a "normal" FLP along the reaction pathway, supported by high-level DFT studies and variable-temperature NMR spectroscopy. These results underscore the possibility of FLP behavior in systems that possess no obvious frustrated Lewis acid-base interaction.

Controlling Proton Delivery through Catalyst Structural Dynamics.

The fastest synthetic molecular catalysts for H2 production and oxidation emulate components of the active site of hydrogenases. The critical role of controlled structural dynamics is recognized for many enzymes, including hydrogenases, but is largely neglected in designing synthetic catalysts. Our results demonstrate the impact of controlling structural dynamics on H2 production rates for [Ni(PPh2 NC6H4R2 )2 ]2+ catalysts (R=n-hexyl, n-decyl, n-tetradecyl, n-octadecyl, phenyl, or cyclohexyl). The turnover frequencies correlate inversely with the rates of chair-boat ring inversion of the ligand, since this dynamic process governs protonation at either catalytically productive or non-productive sites. These results demonstrate that the dynamic processes involved in proton delivery can be controlled through modification of the outer coordination sphere, in a manner similar to the role of the protein architecture in many enzymes. As a design parameter, controlling structural dynamics can increase H2 production rates by three orders of magnitude with a minimal increase in overpotential.

2,6-Diiminopiperidin-1-ol: an overlooked motif relevant to uranyl and transition metal binding on poly(amidoxime) adsorbents.

Glutardiamidoxime, a structural motif on sorbents used in uranium extraction from seawater, was discovered to cyclize in situ at room temperature to 2,6-diimino-piperidin-1-ol in the presence of uranyl nitrate. The new diimino motif was also generated when exposed to competing transition metals Cu(ii) and Ni(ii). Multinuclear µ-O bridged U(vi), Cu(ii), and Ni(ii) complexes featuring bound diimino ligands were isolated.

Frustrated Lewis pair modification by 1,1-carboboration: disclosure of a phosphine oxide triggered nitrogen monoxide addition to an intramolecular P/B frustrated Lewis pair.

The vicinal frustrated Lewis pair (FLP) mes2P-CH2CH2-B(C6F5)2 (3) reacts with phenyl(trimethylsilyl)acetylene by 1,1-carboboration to give the extended C3-bridged FLP 6 featuring a substituted vinylborane subunit. The FLP 6 actively cleaves dihydrogen. The FLP 3 also undergoes a 1,1-carboboration reaction with diphenylphosphino(trimethylsilyl)acetylene to give the P/B/P FLP 11 that features a central unsaturated four-membered heterocyclic P/B FLP and a pendant CH2CH2-Pmes2 functional group. Compound 11 reacts with nitric oxide (NO) by oxidation of the pendant Pmes2 unit to the P(O)mes2 phosphine oxide and N,N-addition of the P/B FLP unit to NO to yield the persistent P/B/PO FLPNO aminoxyl radical 14. This reaction is initiated by P(O)mes2 formation and opening of the central Ph2P···B(C6F5)2 linkage triggered by the pendant CH2CH2-P(O)mes2 group.

Conversion of nitrite to nitric oxide at zinc via S-nitrosothiols.

Nitrite is an important reservoir of nitric oxide activity in the plasma and cells. Using a biomimetic model, we demonstrate the conversion of zinc-bound nitrite in the tris(pyrazolyl)borate complex (iPr2)TpZn(NO2) to the corresponding S-nitrosothiol RSNO and zinc thiolate (iPr2)TpZn-SR via reaction with thiols H-SR. Decomposition of the S-nitrosothiol formed releases nitric oxide gas.

Noninteracting, vicinal frustrated P/B-Lewis pair at the norbornane framework: synthesis, characterization, and reactions.

Hydroboration of dimesitylnorbornenylphosphane with Piers' borane [HB(C6F5)2] gave the frustrated Lewis pair (FLP) 4 in good yield. It has the -PMes2 Lewis base attached at the 2-endo position and the -B(C6F5)2 group 3-exo oriented at the norbornane framework. The vicinal FLP 4 was shown by X-ray diffraction and by spectroscopy to be a rare example of an intramolecular noninteracting pair of a Lewis acid and Lewis base functionality. The FLP 4 rapidly splits dihydrogen heterolytically at ambient temperature to yield the phosphonium/hydrido borate zwitterion 5. It adds to the carbonyl group of benzaldehyde and to carbon dioxide to yield the adducts 6 and 7, respectively. Compounds 5-7 were characterized by X-ray diffraction. Compound 4 adds to the S═O function of sulfur dioxide to give a pair of diastereomeric heterocyclic six-membered ring products due to the newly formed sulfur chirality center, annulated with the norbornane skeleton, which were investigated by (31)P/(11)B single and double resonance solid state NMR experiments. Compound 8 was also characterized by X-ray diffraction. The FLP 4 undergoes a clean N,N-addition to nitric oxide (NO) to give a norbornane annulated five-membered heterocyclic persistent FLP-NO aminoxyl radical 12 (characterized, e.g., by X-ray diffraction and EPR spectroscopy). Additionally, the FLP radical was characterized by (1)H solid state NMR spectroscopy. The radical 12 undergoes a H-atom abstraction reaction with 1,4-cyclohexadiene to yield the respective diamagnetic FLP-NOH product 13, which was also characterized by X-ray diffraction and solid state NMR spectroscopy.

A copper(II) thiolate from reductive cleavage of an S-nitrosothiol.

S-Nitrosothiols RSNO represent circulating reservoirs of nitric oxide activity in the plasma and play intricate roles in protein function control in health and disease. While nitric oxide has been shown to reductively nitrosylate copper(II) centers to form copper(I) complexes and ENO species (E = R(2)N, RO), well-characterized examples of the reverse reaction are rare. Employing the copper(I) ß-diketiminate [Me(2)NN]Cu, we illustrate a clear example in which an RS-NO bond is cleaved to release NO(gas) with formation of a discrete copper(II) thiolate. The addition of Ph(3)CSNO to [Me(2)NN]Cu generates the three-coordinate copper(II) thiolate [Me(2)NN]CuSCPh(3), which is unstable toward free NO.

N,N-addition of frustrated Lewis pairs to nitric oxide: an easy entry to a unique family of aminoxyl radicals.

The intramolecular cyclohexylene-bridged P/B frustrated Lewis pair [Mes(2)P-C(6)H(10)-B(C(6)F(5))(2)] 1b reacts rapidly with NO to give the persistent FLP-NO aminoxyl radical 2b formed by P/B addition to the nitrogen atom of NO. This species was fully characterized by X-ray diffraction, EPR and UV/vis spectroscopies, C,H,N elemental analysis, and DFT calculations. The reactive oxygen-centered radical 2b undergoes a H-atom abstraction (HAA) reaction with 1,4-cyclohexadiene to give the diamagnetic FLP-NOH product 3b. FLP-NO 2b reacts with toluene at 70 °C in an HAA/radical capture sequence to give a 1:1 mixture of FLP-NOH 3b and FLP-NO-CH(2)Ph 4b, both characterized by X-ray diffraction. Structurally related FLPs [Mes(2)P-CHR(1)-CHR(2)-B(C(6)F(5))(2)] 1c, 1d, and 1e react analogously with NO to give the respective persistent FLP-NO radicals 2c, 2d, and 2e, respectively, which show similar HAA and O-functionalization reactions. The FLP-NO-CHMePh 6b derived from 1-bromoethylbenzene undergoes NO-C bond cleavage at 120 °C with an activation energy of E(a) = 35(2) kcal/mol. Species 6b induces the controlled nitroxide-mediated radical polymerization (NMP) of styrene at 130 °C to give polystyrene with a polydispersity index of 1.3. The FLP-NO systems represent a new family of aminoxyl radicals that are easily available by N,N-cycloaddition of C(2)-bridged intramolecular P/B frustrated Lewis pairs to nitric oxide.

Value of radiologic correlation and follow-up scintigraphy in detecting osseous metastasis in patients with non-specific bone scintigraphy lesions

Bone scintigraphy is highly sensitive in detecting bone metastasis but specificity is only about 50-60%. The aim of this study is to evaluate the value of radiologic correlation and followwup scintigraphy in detecting osseous metastasis in patients with equivocal bone scans. Bone scan results with non-specific interpretation of bone lesions from January to December 2007 were included. Results with no evidence of bone metastasis or metastatic bone disease were excluded from the study. Correlation with radiographs [X-ray, CT-scan, MRI] and follow-up bone scan within 6 months from the initial bone scan were reviewed. Of the 2322 bone scans, 435 have non-specific findings of bone lesions. From 435, only 228 patients have records of radiograph correlation and scintigraphic follow-up. Twenty two percent of the total population showed positive findings of bone metastasis in radiographs. The percentages of the non-specific findings determined to be negative from bone metastasis on correlation with X-ray, CT-scan, MRI and follow-up bone scan were 84%, 70%,73%, and 85%, respectively, whereas osseous metastasis revealed on radiologic correlation and follow-up scan were 76%, 30%,27%, and 75%, respectively. In conclusion, the finding of osseous metastasis in bone scan is increased when correlated with radiographs and scintigraphic follow-up.

Metastatic thyroid carcinoma in the kidney

Thyroid carcinoma, particularly papillary thyroid carcinoma, may present with a wide range of clinical course--from an indolent to an aggressive form of poorly differentiated thyroid carcinoma. About 10% of patients with papillary thyroid cancer develop distant metastasis to the lymph nodes, lungs, mediastinum, or bone. Several cases of unusual metastasis to the kidney have been reported previously. A rare case of renal metastasis from papillary thyroid carcinoma and the roles of PET and SPECT-CT in its detection are presented here.