The Effect of Surgical Weight Loss on Cognition in Individuals with Class II/III Obesity.

BACKGROUND: Obesity is a global epidemic and is associated with cognitive impairment and dementia. It remains unknown whether weight loss interventions, such as bariatric surgery, can mitigate cognitive impairment. OBJECTIVES: We aimed to determine the effect of surgical weight loss on cognition in individuals with class II/III obesity. DESIGN: We performed a prospective cohort study of participants who underwent bariatric surgery. At baseline and two years following surgery, participants completed metabolic risk factor and neuropsychological assessments. SETTING: Participants were enrolled from an academic suburban bariatric surgery clinic. PARTICIPANTS: There were 113 participants who completed baseline assessments and 87 completed two-year follow-up assessments (66 in-person and 21 virtual) after bariatric surgery. The mean (SD) age was 46.8 (12.5) years and 64 (73.6%) were female. INTERVENTION: Bariatric surgery. There were 77 (88.5%) participants that underwent sleeve gastrectomy and 10 (11.5%) that underwent gastric bypass surgery. MEASUREMENTS: Cognition was assessed using the NIH toolbox cognitive battery (NIHTB-CB) and the Rey Auditory Verbal Learning Test (AVLT). The primary outcome was the change in NIHTB-CB fluid composite score before and after surgery. RESULTS: The primary outcome, NIHTB-CB composite score, was stable following bariatric surgery (-0.4 (13.9), p=0.81,n=66). Among secondary outcomes, the NIHTB-CB dimensional card sorting test (executive function assessment), improved (+6.5 (19.9),p=0.01,n=66) while the Rey AVLT delayed recall test (memory assessment) declined (-0.24 (0.83),p=0.01,n=87) following surgery. Improvements to metabolic risk factors and diabetes complications were not associated with improvements to NIHTB-CB composite score. The other 4 NIHTB-CB subtests and Rey AVLT assessments of auditory learning and recognition were stable at follow-up. CONCLUSIONS: Following bariatric surgery, the age-adjusted composite cognitive outcome did not change, but an executive subtest score improved. These results suggest that bariatric surgery may mitigate the natural history of cognitive decline in individuals with obesity, which is expected to be faster than normal aging, but confirmatory randomized controlled trials are needed. The decline in delayed recall also warrants further studies to determine potential differential effects on cognitive subtests.

First Observation of Electron Scattering from Online-Produced Radioactive Target.

We successfully performed electron scattering off unstable nuclei which were produced online from the photofission of uranium. The target ^{137}Cs ions were trapped with a new target-forming technique that makes a high-density stationary target from a small number of ions by confining them in an electron storage ring. After developments of target generation and transportation systems and the beam stacking method to increase the ion beam intensity up to approximately 2×10^{7} ions per pulse beam, an average luminosity of 0.9×10^{26} cm^{-2} s^{-1} was achieved for ^{137}Cs. The obtained angular distribution of elastically scattered electrons is consistent with a calculation. This success marks the realization of the anticipated femtoscope which clarifies the structures of exotic and short-lived unstable nuclei.

Multiple intra-articular injections with adipose-derived stem cells for knee osteoarthritis cause severe arthritis with anti-histone H2B antibody production.

Introduction: Osteoarthritis (OA) is the most common form of arthritis. OA results from the breakdown of cartilage, which leads to deterioration of the entire joint and the connective tissue that holds the joint together, and gradually and irreversibly worsens over time. Adipose-derived stem/stromal cells (ADSCs) have been used in the treatment of knee OA. However, the safety and efficacy of ADSC treatment of OA remain unclear. In this study, we investigated the pathophysiology of severe knee arthritis that occurred after ADSC treatment by screening for autoantibodies in synovial fluid from patients who received ADSC treatment. Methods: Adult Japanese patients with OA who received ADSC treatment at Saitama Cooperative Hospital between June 2018 and October 2021 were enrolled. Antibodies (Abs) were screened using immunoprecipitation (IPP) with [35S]-methionine-labeled HeLa cell extracts. The detected protein was identified by liquid chromatography coupled with time-of-flight mass spectrometry (MS) and ion trap MS, and the corresponding proteins were confirmed as autoantigens using immunoblotting. Ab titers were measured using an enzyme-linked immunosorbent assay. Results: A total of 113 patients received ADSC treatment, and 75% (85/113) received ADSC injection at least twice with a 6-month interval between. No obvious abnormalities were observed in any patient after their first treatment; by contrast, 53% (45/85) of patients who received their second or third ADSC injection showed severe knee arthritis. IPP detected a common anti-15 kDa Ab in synovial fluid of 62% (8/13) of the samples analyzed from patients who showed severe arthritis. This Ab was not detected in synovial fluid obtained from the same joints before treatment. The corresponding autoantigen was identified as histone H2B. All available synovial samples from patients who tested positive for anti-histone H2B Ab were newly positive after the treatment; that is, none had been positive for anti-histone H2B Ab before treatment. Conclusions: Multiple ADSC injections for OA induced severe arthritis in a high percentage of patients, particularly after the second injection. Synovial fluid from some patients with knee arthritis contained Ab to histone H2B that appeared only after ADSC treatment. These findings provide new insights into the pathogenesis of ADSC treatment-induced severe arthritis.

TRIM27 expression is associated with poor prognosis in sinonasal mucosal melanoma.

BACKGROUND: Tripartite motif-containing 27 (TRIM27) has been implicated in the progression of various cancers. However, the role of TRIM27 in sinonasal mucosal melanoma (SNMM) remains poorly understood. MATERIALS & METHODS: We retrospectively examined 28 patients with SNMM treated with between 2003 and 2021. We undertook immunohistochemical analysis of TRIM27, Ki-67, and p-Akt1 expression in SNMM tissues. We also investigated the relationship between TRIM27 expression and clinical characteristics, prognosis, Ki-67 as a tumor growth potential marker, and p-Akt1 as one of the prognostic factors in mucosal melanoma. RESULTS: TRIM27 expression was significantly higher in T4 disease than in T3 disease and was higher in stage IV than in stage III. Patients with high-TRIM27 SNMM had a significantly poorer prognosis in terms of overall survival (OS) and disease-free survival.There was also a significantly higher rate of distant metastasis. Univariate analysis for OS revealed that TRIM27 and T classification were significant poor prognostic factors. In addition, the Ki-67 positive score and the p-Akt1 total staining score were significantly higher in the high-TRIM27 group than in the low-TRIM27 group. CONCLUSIONS: High TRIM27 expression in SNMM was associated with advanced T classification, poor prognosis and distant metastasis. We suggest that TRIM27 has potential as a novel biomarker for prognosis in SNMM.

Development of Rat Caries-Induced Pulpitis Model for Vital Pulp Therapy.

Rodent animal models for vital pulp therapy are commonly used in dental research because their tooth anatomy and cellular processes are similar to the anatomy and processes in humans. However, most studies have been conducted using uninfected sound teeth, which makes it difficult to adequately assess the inflammatory shift after vital pulp therapy. In the present study, we aimed to establish a caries-induced pulpitis model based on the conventional rat caries model and then evaluate inflammatory changes during the wound-healing process after pulp capping in a model of reversible pulpitis induced by carious infection. To establish the caries-induced pulpitis model, the pulpal inflammatory status was investigated at different stages of caries progression by immunostaining targeted to specific inflammatory biomarkers. Immunohistochemical staining revealed that both Toll-like receptor 2 and proliferating cell nuclear antigen were expressed in moderate and severe caries-stimulated pulp, indicating that an immune reaction occurred at both stages of caries progression. M2 macrophages were predominant in moderate caries-stimulated pulp, whereas M1 macrophages were predominant in the severe caries-stimulated pulp. Pulp capping in teeth with moderate caries (i.e., teeth with reversible pulpitis) led to complete tertiary dentin formation within 28 d after treatment. Impaired wound healing was observed in teeth with severe caries (i.e., teeth with irreversible pulpitis). During the wound-healing process in reversible pulpitis after pulp capping, M2 macrophages were predominant at all time points; their proliferative capacity was upregulated in the early stage of wound healing compared with healthy pulp. In conclusion, we successfully established a caries-induced pulpitis model for studies of vital pulp therapy. M2 macrophages have an important role in the early stages of the wound-healing process in reversible pulpitis.

Novel Functional Peptide for Next-Generation Vital Pulp Therapy.

Although vital pulp therapy should be performed by promoting the wound-healing capacity of dental pulp, existing pulp-capping materials were not developed with a focus on the pulpal repair process. In previous investigations of wound healing in dental pulp, we found that organic dentin matrix components (DMCs) were degraded by matrix metalloproteinase-20, and DMC degradation products containing protein S100A7 (S100A7) and protein S100A8 (S100A8) promoted the pulpal wound-healing process. However, the direct use of recombinant proteins as pulp-capping materials may cause clinical problems or lead to high medical costs. Thus, we hypothesized that functional peptides derived from recombinant proteins could solve the problems associated with direct use of such proteins. In this study, we identified functional peptides derived from the protein S100 family and investigated their effects on dental pulp tissue. We first performed amino acid sequence alignments of protein S100 family members from several mammalian sources, then identified candidate peptides. Next, we used a peptide array method that involved human dental pulp stem cells (hDPSCs) to evaluate the mineralization-inducing ability of each peptide. Our results supported the selection of 4 candidate functional peptides derived from proteins S100A8 and S100A9. Direct pulp-capping experiments in a rat model demonstrated that 1 S100A8-derived peptide induced greater tertiary dentin formation compared with the other peptides. To investigate the mechanism underlying this induction effect, we performed liquid chromatography-tandem mass spectrometry analysis using hDPSCs and the S100A8-derived peptide; the results suggested that this peptide promotes tertiary dentin formation by inhibiting inflammatory responses. In addition, this peptide was located in a hairpin region on the surface of S100A8 and could function by direct interaction with other molecules. In summary, this study demonstrated that a S100A8-derived functional peptide promoted wound healing in dental pulp; our findings provide insights for the development of next-generation biological vital pulp therapies.

The role of thyroid function in female and male infertility: a narrative review.

PURPOSE: We herein aimed to review the new insights into the impact of impaired thyroid function on male and female fertility, spacing from spontaneous pregnancy to ART, with the objective of providing an updated narrative revision of the literature. METHODS: This narrative review was performed for all available prospective, retrospective and review articles, published up to 2021 in PubMed. Data were extracted from the text and from the tables of the manuscript. RESULTS: Thyroid dysfunction is frequently associated with female infertility, whereas its link with male infertility is debated. Female wise, impaired function is detrimental to obstetric and fetal outcomes both in spontaneous pregnancies and in those achieved thanks to assisted reproduction technologies (ART). Furthermore, the reference range of TSH in natural pregnancy and ART procedures has recently become a matter of debate following recent reports in this field. On the other hand, the impact of thyroid function on the male reproductive system is less clear, although a possible role is suggested via modulation of Sertoli and Leydig cells function and spermatogenesis. CONCLUSION: Thyroid function should be carefully monitored in both male and female, in couples seeking spontaneous pregnancy as well as ART, as treatment is generally immediate and likely to improve chances of success.

SWI by 7T MR Imaging for the Microscopic Imaging Diagnosis of Astrocytic and Oligodendroglial Tumors.

BACKGROUND AND PURPOSE: Despite advances in molecular imaging, preoperative diagnosis of astrocytomas and oligodendrogliomas can be challenging. In the present study, we assessed whether 7T SWI can be used to distinguish astrocytomas and oligodendrogliomas and whether malignant grading of gliomas is possible. MATERIALS AND METHODS: 7T SWI was performed on 21 patients with gliomas before surgery with optimization for sharp visualization of the corticomedullary junction. Scoring for cortical thickening and displacement of medullary vessels, characteristic of oligodendroglial tumors, and cortical tapering, characteristic of astrocytic tumors, was performed. Additionally, characteristics of malignancy, including thickening of the medullary veins, the presence of microbleeds, and/or necrosis were scored. RESULTS: Scoring for oligodendroglial (highest possible score, +3) and astrocytic (lowest score possible, -3) characteristics yielded a significant difference between astrocytomas and oligodendrogliomas (mean, -1.93 versus +1.71, P < .01). Scoring for malignancy was significantly different among the World Health Organization grade II (n = 10), grade III (n = 4), and grade IV (n = 7) tumors (mean, 0.20 versus 1.38 versus 2.79). Cortical thickening was observed significantly more frequently in oligodendrogliomas (P < .02), with a sensitivity of 71.4% and specificity of 85.7%; observation of tapering of the cortex was higher in astrocytomas (P < .01) with a sensitivity of 85.7% and specificity of 100%. CONCLUSIONS: Visualization of the corticomedullary junction by 7T SWI was useful in distinguishing astrocytomas and oligodendrogliomas. Observation of tapering of the cortex was most sensitive and specific for diagnosing astrocytomas. Reliably predicting malignant grade was also possible by 7T SWI.

Spatial resolution in transmission electron microscopy.

We review the practical factors that determine the spatial resolution of transmission electron microscopy (TEM) and scanning-transmission electron microscopy (STEM), then enumerate the advantages of representing resolution in terms of a point-spread function. PSFs are given for the major resolution-limiting factors: aperture diffraction, spherical and chromatic aberration, beam divergence, beam broadening, Coulomb delocalization, radiolysis damage and secondary-electron generation from adatoms or atoms in a matrix. We note various definitions of beam broadening, complications of describing this effect in very thin specimens, and ways of optimizing the resolution in bright-field STEM of thick samples. Beam spreading in amorphous and crystalline materials is compared by means of simulations. For beam-sensitive specimens, we emphasize the importance of dose-limited resolution (DLR) and briefly recognize efforts to overcome the fundamental resolution limits set by the wave and particle properties of electrons.

Feline platynosomiasis in Klang Valley, Malaysia: Diagnosis, pathology and management.

Platynosomum fastosum (synonym Platynosomum concinnum, Platynosomum illiciens ) is a hepatic fluke causing platynosomiasis or 'lizard poisoning' in cats. This disease is generally being underestimated by veterinary practitioners due to lack of awareness and difficulty in diagnosis although the severe cases of platynosomiasis could be fatal. This study was designed to detect the presence of cat liver fluke through faecal examination among cats kept in shelters, pet cats and stray cats around Klang Valley, Malaysia. The detection of liver flukes among stray cats was based on post-mortem examination. A total of 201 faecal samples were collected from eight shelters (n = 119) and five veterinary clinics (n = 82) in Klang Valley were subjected to simple floatation and formalin-ether sedimentation techniques for ova detection. P. fastosum ova were identified in three faecal samples obtained from shelters (2.52%) and three samples collected from veterinary clinics (3.66%) by faecal examination. A total of 51 stray cats were procured from Pest and Animal Control Unit of the respective municipality. The cats were euthanised and necropsied to collect liver samples and bile duct. The liver was then dissected for isolation and identification of the fluke and bile duct fluid were aspirated for detection of fluke ova. Twelve cats (23.5%) were positive for P. fastosum and ova were found in their bile. Macroscopically, affected cats showed mottled liver (33.3%), distended gall bladder with thick tenacious bile (66.7%) that microscopically exhibited hepatic steatosis (25.0%) and hepatitis (33.3%). The severity of parasite load was almost equally distributed between the positive cats with low (n = 5, 55.6%; > 125 adult fluke) and high parasite burden (n = 4, 44.4%; < 125 adult fluke) cats, respectively. This study revealed the detection of P. fastosum among pet, shelters and stray cats in Klang Valley, Malaysia.

Evolution in X-ray analysis from micro to atomic scales in aberration-corrected scanning transmission electron microscopes.

X-ray analysis is one of the most robust approaches to extract quantitative information from various materials and is widely used in various fields ever since Raimond Castaing established procedures to analyze electron-induced X-ray signals for materials characterization '70 years ago'. The recent development of aberration-correction technology in a (scanning) transmission electron microscopes (S/TEMs) offers refined electron probes below the Å level, making atomic-resolution X-ray analysis possible. In addition, the latest silicon drift detectors allow complex detector arrangements and new configurational designs to maximize the collection efficiency of X-ray signals, which make it feasible to acquire X-ray signals from single atoms. In this review paper, recent progress and advantages related to S/TEM-based X-ray analysis will be discussed: (i) progress in quantification for materials characterization including the recent applications to light element analysis, (ii) progress in analytical spatial resolution for atomic-resolution analysis and (iii) progress in analytical sensitivity toward single-atom detection and analysis in materials. Both atomic-resolution analysis and single-atom analysis are evaluated theoretically through multislice-based calculation for electron propagation in oriented crystalline specimen in combination with X-ray spectrum simulation.

Renoprotective effect of N-acetylcysteine depends upon the severity of the ischemia reperfusion injury.

Acute kidney injury (AKI) is a common complication in seriously ill patients, while renal ischemia-reperfusion (I/R) injury is the most frequent event in this oxidative renal injury. N-acetylcysteine (NAC) is a small molecule containing a thiol group that has antioxidant properties, promoting detoxification and acting directly as a free radical scavenger. In this study, the protective effect of NAC was investigated in short-term (30 min) and long-term (45 min) ischemic AKI. This was achieved via clamping of the renal artery for 30 or 45 min in Wistar rats to induce I/R injury. AKI worsened with a longer period of ischemia (45 compared to 30 min) due to probable irreversible damage. Preconditioning with NAC in short-term ischemia improved renal blood flow and increased creatinine clearance by reducing oxidative metabolites and increasing antioxidant capacity. Otherwise, NAC did not change these parameters in the long-term ischemia. Therefore, this study demonstrated that the period of ischemia determines the severity of the AKI, and NAC presented antioxidant effects in short-term ischemia but not in long-term ischemia, confirming that there is a possible therapeutic window for its renoprotective effect.

Safety and feasibility of laparoscopic surgery for elderly rectal cancer patients in Japan: a nationwide study.

BACKGROUND: This study aimed to analyse the perioperative results from a national dataset of rectal cancer resections in elderly patients. METHODS: The clinical records of patients undergoing rectal cancer surgery between 2012 and 2014 were retrieved from the Japanese National Clinical Database and analysed retrospectively. Patients were categorized according to age and those 80 years or older were defined as elderly. Subgroups were also defined according to the surgical approach (laparoscopy versus open surgery). The short-term outcomes, including mortality, anastomotic leak, surgical site infections and medical complications were compared between subgroups. RESULTS: Of 56 175 patients undergoing rectal cancer surgery, some 6717 patients were elderly and laparoscopy was performed in 46.8 per cent of the sample. When comparing laparoscopy and open surgery in elderly patients, the operative mortality rate (1.5 versus 2.8 per cent; P < 0.001), the incidence of anastomotic leakage (5.2 versus 6.5 per cent; P = 0.026), surgical site infections (6.0 versus 8.0 per cent; P = 0.001), pneumonia (1.4 versus 2.5 per cent; P = 0.001), renal failure (0.7 versus 1.3 per cent; P = 0.016) and cardiac events (0.3 versus 0.8 per cent; P = 0.008) were lower for laparoscopy than for open surgery. The overall complication rate in elderly patients (19.5 per cent) was comparable to that in the younger group (P = 0.07). However, incidence of systemic complications was significantly higher in elderly than in younger patients (all P < 0.001). CONCLUSION: Laparoscopy was safe and feasible in elderly patients compared with open surgery. However, the rates of systemic complications were significantly higher than in younger patients.

Renoprotective effect of N-acetylcysteine depends upon the severity of the ischemia reperfusion injury

Acute kidney injury (AKI) is a common complication in seriously ill patients, while renal ischemia-reperfusion (I/R) injury is the most frequent event in this oxidative renal injury. N-acetylcysteine (NAC) is a small molecule containing a thiol group that has antioxidant properties, promoting detoxification and acting directly as a free radical scavenger. In this study, the protective effect of NAC was investigated in short-term (30 min) and long-term (45 min) ischemic AKI. This was achieved via clamping of the renal artery for 30 or 45 min in Wistar rats to induce I/R injury. AKI worsened with a longer period of ischemia (45 compared to 30 min) due to probable irreversible damage. Preconditioning with NAC in short-term ischemia improved renal blood flow and increased creatinine clearance by reducing oxidative metabolites and increasing antioxidant capacity. Otherwise, NAC did not change these parameters in the long-term ischemia. Therefore, this study demonstrated that the period of ischemia determines the severity of the AKI, and NAC presented antioxidant effects in short-term ischemia but not in long-term ischemia, confirming that there is a possible therapeutic window for its renoprotective effect.

An Assessment of Earth's Climate Sensitivity Using Multiple Lines of Evidence.

We assess evidence relevant to Earth's equilibrium climate sensitivity per doubling of atmospheric CO2, characterized by an effective sensitivity S. This evidence includes feedback process understanding, the historical climate record, and the paleoclimate record. An S value lower than 2 K is difficult to reconcile with any of the three lines of evidence. The amount of cooling during the Last Glacial Maximum provides strong evidence against values of S greater than 4.5 K. Other lines of evidence in combination also show that this is relatively unlikely. We use a Bayesian approach to produce a probability density function (PDF) for S given all the evidence, including tests of robustness to difficult-to-quantify uncertainties and different priors. The 66% range is 2.6-3.9 K for our Baseline calculation and remains within 2.3-4.5 K under the robustness tests; corresponding 5-95% ranges are 2.3-4.7 K, bounded by 2.0-5.7 K (although such high-confidence ranges should be regarded more cautiously). This indicates a stronger constraint on S than reported in past assessments, by lifting the low end of the range. This narrowing occurs because the three lines of evidence agree and are judged to be largely independent and because of greater confidence in understanding feedback processes and in combining evidence. We identify promising avenues for further narrowing the range in S, in particular using comprehensive models and process understanding to address limitations in the traditional forcing-feedback paradigm for interpreting past changes.