Triglyceride-Glucose Index Associated with Future Renal Function Decline in the General Population.

BACKGROUND: The triglyceride-glucose index (TyG index), calculated as the logarithmic product of fasting triglyceride and glucose concentrations, is recognized as a simple marker of insulin resistance. However, the association between the TyG index and future decline of renal function remains unclear in the general population. OBJECTIVE: To investigate whether the TyG index was associated with future decline of renal function in the general population who had not progressed to chronic kidney disease stage G2. DESIGN: Retrospective longitudinal observational cohort study. PARTICIPANTS: Individuals who received a population-based health checkup at JA Ehime Kouseiren Checkup Center from 2010 to 2019 (n = 134,007). Individuals without data of baseline fasting triglyceride or glucose levels, or baseline and follow-up data of estimated glomerular filtration rate (eGFR), or those with baseline eGFR < 60 mL/min/1.73 m2 were excluded. MAIN MEASURES: Future renal function decline, defined as a ≥ 25% decrease in eGFR from baseline. KEY RESULTS: Of 10,758 participants, 8,076 were classified into the low TyG index group (TyG index < 8.76, 1st to 3rd quartiles) and 2,682 into the high TyG index group (TyG index ≥ 8.76, 4th quartile). The mean follow-up period was 37.8 ± 23.6 months. The incidence rates of renal function decline were 0.31 and 0.69 per 100 person-years in the low and high TyG index groups, respectively. In multivariate Cox proportional hazard models, high TyG index was significantly associated with future renal function decline (hazard ratio 2.25, 95% CI 1.40-3.60). This association was consistent across subgroups stratified by age, sex, body mass index, baseline eGFR, and diagnosed hypertension, diabetes, or dyslipidemia. CONCLUSION: In the general population, high TyG index was associated with future renal function decline. The TyG index may be useful in identifying individuals at high risk for future renal function decline in the setting of health checkups.

Impact of comprehensive geriatric assessment on treatment strategies and complications in older adults with colorectal cancer considering surgery.

BACKGROUND AND OBJECTIVES: This study aimed to assess the effectiveness of Comprehensive Geriatric Assessment (CGA) in customizing care for elderly cancer patients, specifically focusing on colorectal cancer. The research compared treatment strategies and outcomes in older adults considered for surgery before and after the initiation of a Geriatric Oncology Service (GOS). METHODS: Conducting a comparative study, two cohorts of consecutive colorectal cancer patients aged 75 or older were examined: the control group (n = 156) and the GOS group (n = 158). Upon the treating surgeon's GOS consultation request, a geriatrician and an oncologist performed CGA, guiding treatment decisions and perioperative interventions. Postoperative complications were compared using propensity score matching (PSM). RESULTS: In the GOS group, 91% (n = 116) underwent CGA consultations, influencing decisions to forego surgery in 12 patients. After PSM for surgical cases (controls n = 146, GOS n = 146), each group comprised 128 patients. Perioperative physical therapy and pharmacist referrals were more frequent in the GOS group. The GOS group exhibited a significantly lower incidence of postoperative complications (22%) compared to the control group (33%) (p = 0.0496). CONCLUSION: Patients undergoing colorectal surgery post-GOS implementation experienced a notable reduction in postoperative complications, highlighting the positive impact of personalized geriatric assessment on surgical outcomes in the elderly.

Frequency-multiplexed on-demand storage in five modes of atomic frequency comb through simultaneous application of control pulses.

In quantum communication with quantum repeaters, multiplexed quantum memory is expected to enhance communication rates. When using an atomic frequency comb (AFC) for on-demand storage, the frequency mode number is often limited by the optical power of the control pulses. Here, using a space-coupled waveguide electro-optic modulator, we increased the output power, allowing us to apply control pulses to multiple modes simultaneously. Further, through enhancement of an experimental setup that increases power density, we increased the number of modes. Consequently, we pioneered, to the best of our knowledge, on-demand storage using five modes of AFC. This technology is a significant achievement toward frequency-multiplexed on-demand quantum memory.

Incidence and characteristics of aspiration pneumonia in the Nagasaki Prefecture from 2005 to 2019.

BACKGROUND: Aspiration pneumoniae remains a major health concern, particularly in the older population and has poor prognosis; however, the concept itself remains vague worldwide. This study aimed to determine the actual situation and characteristics of aspiration pneumonia from 2005 to 2019 in Nagasaki Prefecture, Japan. METHODS: Cases of aspiration pneumonia that occurred in the Nagasaki Prefecture between 2005 and 2019 were analyzed using emergency transportation records. The number of occurrences and incidence were analyzed according to age, sex, month, day of the week, and recognition time to clarify the actual situation of aspiration pneumonia. RESULTS: The total number of new aspiration pneumonia cases was 8,321, and the mean age of the patients was 83.0 years. Annual incidence per 100,000 population increased from 12.4 in 2005 to 65.1 in 2019, with the most prominent increase in the ≥ 80-year-old stratum. Males (55.1%) were more commonly affected than females (44.9%), and 82.2% of the cases involved patients aged ≥ 70 years. No significant correlations were observed between the incidence of aspiration pneumonia and season, month, or day of the week. Aspiration pneumonia occurred frequently in houses (39.8%) and facilities for elderly individuals (40.8%). At 7 days after admission, 80.9% of patients were still hospitalized and 6.5% had died. CONCLUSIONS: The incidence of aspiration pneumonia with risks of severity and mortality is increasing among elderly individuals. Valid preventive measures are urgently needed based on the findings that the disease occurs in both household and elderly care facility settings, regardless of the season.

Stability and bonding nature of positronic lithium molecular dianion.

We studied the stability of a system consisting of a positron (e+) and two lithium anions, [Li-; e+; Li-], using first-principles quantum Monte Carlo calculations combined with the multi-component molecular orbital method. While diatomic lithium molecular dianions Li22- are unstable, we found that its positronic complex can form a bound state with respect to the lowest energy decay into the dissociation channel Li2- and a positronium (Ps). The [Li-; e+; Li-] system has the minimum energy at the internuclear distance of ∼3 Å, which is close to the equilibrium internuclear distance of Li2-. At the minimum energy structure both an excess electron and a positron are delocalized as orbiting around the Li2- molecular anion core. A dominant feature of such a positron bonding structure is described as the Ps fraction bound to Li2-, unlike the covalent positron bonding scheme for the electronically isovalent [H-; e+; H-] complex.

The superselective intra-arterial infusion of cisplatin and concomitant radiotherapy (RADPLAT) is effective for metastatic lymph nodes in head and neck squamous cell carcinoma.

BACKGROUND: Superselective intra-arterial infusion of cisplatin and concomitant radiotherapy (RADPLAT) is a very promising treatment modality for locally advanced head and neck squamous cell carcinoma. However, there are some concerns regarding its potential for the control of neck lymph node metastasis. The objective of this study was to investigate whether RADPLAT provided inferior regional control compared to intravenous chemoradiotherapy (IV-CRT). METHODS: A total of 172 patients with neck lymph node metastases, 66 of whom underwent RADPLAT and 106 IV-CRT, were enrolled in this study. We retrospectively compared regional control rates between RADPLAT and IV-CRT. Furthermore, to adjust for differences in factors related to patient background between the groups, we conducted inverse probability weighting (IPW) analysis using the propensity score. RESULTS: A comparison between the two groups revealed that the regional control rates were almost equal under unadjusted conditions; however, after adjustment by IPW analysis, the RADPLAT group had a relatively better regional control rate than did the IV-CRT group (1 year regional control rate: 86.6% vs. 79.4%). In addition, the analysis of relative risk factors for regional control in the RADPLAT group showed that the absence of intra-arterial cisplatin infusion into metastatic lymph nodes was the only independent risk factor (Hazard ratio: 4.23, p = 0.04). CONCLUSION: This study showed that the regional control rate in patients treated with RADPLAT was noninferior to that for IV-CRT. Locally advanced head and neck cancers is a good indication for RADPLAT, even if the patients have neck lymph node metastases.

[Recurrence of a Giant Emphysematous Bulla After Bullectomy:Report of a Case].

A 38-year-old male, he was diagnosed with a giant pulmonary bulla occupying 2/3 of the right thoracic cavity on chest computed tomography( CT). The preoperative pulmonary function was unfavorable, so bullectomy of right upper lobe with video-assisted thoracoscopic surgery( VATS) was performed. The outpatient follow-up was completed at 6 months after surgery. However, one year and eleven months postoperatively, the patient returned to the clinic complaining of dyspnea. Chest X-ray and CT showed a recurrence of a giant emphysematous bulla in the right upper lobe. Two years and three months after the initial surgery, the recurrent giant bulla was resected by right upper lobectomy with VATS. About four years after the reoperation, no recurrence of giant pulmonary bulla has been seen. Although there are some reports on surgical treatment and results of giant pulmonary bulla, there are few reports on recurrent cases, so we report this case.

A comprehensive theoretical study of positron binding and annihilation properties of hydrogen bonded binary molecular clusters.

We studied the positron binding and annihilation of hydrogen bonded binary molecular clusters containing small inorganic molecules such as water, hydrogen fluoride, ammonia, hydrogen sulfide, hydrogen chloride, and phosphine, using first-principles calculation. While unimolecular systems of these species mostly exhibit no or very small positron binding energies (positron affinities), we found that all of their hydrogen bonding clusters have greater positive positron affinities. The permanent dipole moment enhanced by the formation of the intermolecular hydrogen bond acts as a dominant parameter to bind a positron for a given proton donor, whereas it is insufficient for reproducing the dependence of the positron affinity on substitutions of the proton donor. By multiple regression analyses with inherent properties of the clusters, we found a reasonable model with additional effective parameters represented by, particularly, the number of hydrogen atoms free from the hydrogen bond. By density analyses for the single-particle and electron-positron collision probabilities, we revealed that these effective parameters are associated with the electronic structure changes induced by the hydrogen bond and positron binding, which have important roles to enhance the electron-positron contact densities due to the proton-screening effect.

Theoretical investigations of positron affinities and their structure-dependent properties of carbon dioxide clusters (CO2)n (n = 1-5).

Although positron binding to van der Waals intermolecularly bonded clusters of non-polar carbon dioxide (CO2) molecules was experimentally suggested, the positron binding feature has been poorly understood. We investigated positron affinities (PAs) by means of multi-component configuration interaction calculations for various structures of (CO2)n (n = 1-5) obtained by the single-component artificial force induced reaction (SC-AFIR) method. Our calculations showed that CO2 monomers do not bind a positron, whereas positron affinities for clusters tend to increase with an increase in the cluster size. Our regression analyses for determining PAs with electrostatic and structural properties of conformations revealed a significant conformer effect due to which structural characteristics such as flatness may have a strong influence on PA for loosely bound positronic complexes of (CO2)n.

Chronological changes of serum exosome in preterm infants: A prospective study.

BACKGROUND: Exosomes, which are observed in all human fluid, including serum, are nanosized extracellular vesicles with a mechanism of intercellular communication. Potential clinical applications of exosomes in neonatal diseases have recently been discussed. However, the characteristics of exosomes in serum during early infancy is unclear. METHODS: In this prospective study, we evaluated the chronological changes in the concentration of serum-derived exosomes of 20 infants for 12 months after birth. RESULTS: The average concentration of serum-derived exosomes was 4.6 × 1010 particles/mL at birth and increased significantly until the age of 48 weeks. There was a moderate correlation between the gestational age and the concentration of serum-derived exosomes both at birth (r = 0.54, P = 0.01) and during the 8 weeks after birth (r = 0.48, P < 0.001). A multivariable analysis showed that gestational age at birth was associated with the concentration of serum-derived exosomes at birth (partial regression coefficient, 0.86; 95% confidence interval, 0.37-1.37; P = 0.002). CONCLUSIONS: The concentration of serum-derived exosomes in preterm infants increased both chronologically and by gestational age after birth. These basic data may help to further understand physiology of exosomes in preterm infants.

Salvage surgery improves the treatment outcome of patients with residual/recurrent maxillary sinus cancer after superselective intra-arterial cisplatin infusion with concomitant radiation therapy.

PURPOSE: We have performed superselective intra-arterial cisplatin infusion with concomitant radiotherapy (RADPLAT) for patients with maxillary sinus cancer. The promising treatment outcomes of this non-surgical treatment were reported in past studies. However, few clinical studies have been conducted to evaluate the outcome of salvage surgery following RADPLAT. The purpose of this study was to analyze the treatment outcomes of salvage surgery for patients with recurrent maxillary sinus cancer after RADPLAT. METHODS: We assessed 45 patients who had recurrence following RADPLAT between 1999 and 2017, and conducted a retrospective analysis. We excluded patients who did not complete RADPLAT. Patients were not considered to have completed RADPLAT if they underwent intra-arterial cisplatin less than three times or received a total radiation dose of less than 60 Gy. The primary endpoint was overall survival. The median follow-up period for surviving patients after recurrence was 5.1 years. RESULTS: Twenty-five of the 45 (56%) patients underwent salvage surgery. The 5-year overall survival rate was 68% in patients who underwent salvage surgery, while all patients who did not undergo salvage surgery died during the observation period. Fifteen of 24 (63%) patients with local recurrence underwent salvage surgery. Eight patients did not undergo salvage surgery because of unresectable disease; five of the eight patients had unresectable posterior extension. All nine patients with nodal recurrence underwent neck dissection. CONCLUSION: Treatment outcomes of salvage surgery following RADPLAT were favorable enough for it to be generally recommended. To reduce unresectable recurrence, the posterior section should be eradicated by RADPLAT.

Changes in regional oxygen saturation of the kidney and brain of infants during hospitalization.

BACKGROUND: In pre-term infants, the postnatal changes in the regional oxygen saturation (rSO2) of the brain and kidney are unclear. METHODS: We performed a prospective observational study. We measured the cerebral/renal rSO2 ratio and recorded the associated clinical features of infants born at 23 to 41 weeks of gestation weekly from the early postnatal period to discharge. RESULTS: The median cerebral/renal rSO2 ratios (interquartile ranges) between birth and the expected date of birth were 1.13 (1.06-1.26) at 23-24 weeks (n = 7), 1.18 (1.10-1.32) at 25-26 weeks (n = 11), 1.24 (1.11-1.37) at 27-28 weeks (n = 9), 1.12 (1.05-1.19) at 29-30 weeks (n = 4), 1.11 (1.03-1.15) at 31-32 weeks (n = 5), 1.02 (0.98-1.06) at 33-34 weeks (n = 9), 0.98 (0.94-1.06) at 35-36 weeks (n = 19), and 0.95 (0.86-0.99) at 37-41 weeks of gestation (n = 22). The median cerebral/renal rSO2 ratio did not significantly change after birth, but with increasing gestational age, the cerebral/renal rSO2 ratio at the expected date of birth decreased (r = - 0.74, p < 0.001). Nephrotoxic drugs did not affect cerebral/renal rSO2 at the expected date of birth, after adjustment for clinical factors. CONCLUSIONS: Unlike in most infants born after the late pre-term period, the renal rSO2 remained lower than the cerebral rSO2 on the expected date of birth in infants born very pre-term.

Theoretical investigation of the enhancement of positron affinity by the vibration and dimerization of non-polar carbon disulfide.

The positronic bound state for the non-polar carbon disulfide (CS2) has been experimentally identified, although previous theoretical investigations, which were dedicated to studying the positronic CS2 monomer, could not reasonably reproduce the experimentally measured positron affinity. In the present study, we performed analysis of the vibrational averaged positron affinity for the positronic CS2 dimer, [C2S4; e+], using the Hartree-Fock and configuration interaction levels of the multi-component molecular orbital method combined with the self-consistent field level of the vibrational variational Monte Carlo method. We demonstrated that the equilibrium structure of the non-polar C2S4 can have the positronic bound state with a positron affinity of about 46.18 meV in the configuration interaction level, while this is 0 meV in the Hartree-Fock level. Furthermore, by taking into account the vibrational effect, we succeeded in reproducing the resonant positron kinetic energies lying close to the experimental value, where the vibrational averaged positron affinity becomes greater with an increased dipole moment and dipole polarizability. We also showed possible mechanisms to effectively enhance the resonant positron capture for [C2S4; e+], associated with both the infrared active and infrared inactive vibrational modes.

Prognostic Impact of the Neutrophil-to-Lymphocyte Ratio in Stage I-II Rectal Cancer Patients.

BACKGROUND: Systemic inflammation and immune response play crucial roles in tumor growth; neutrophil-to-lymphocyte ratio (NLR) is a known systemic inflammatory scoring system. Previous studies have reported that NLR is a prognostic biomarker in various human cancers. The aim of this study was to determine whether the NLR predicts tumor recurrence in patients with stage I-II rectal cancer after curative resection. METHODS: We retrospectively analyzed 130 consecutive patients with stage I-II rectal cancer who underwent curative resection between January 2006 and March 2015 at our institution without any preoperative treatment. We investigated whether clinicopathologic factors including NLR were associated with cancer recurrence after curative surgery. RESULTS: There were four cases (3.1%) of cancer-specific deaths and 16 cases (12.3%) of recurrence; the 5-year disease-free survival rate was 85.6%. NLR, pathologic T-category, and lymphatic invasion were significantly associated with disease-free survival. Multivariate analysis further showed that these three factors were independently associated with disease-free survival. CONCLUSIONS: Preoperative NLR could predict tumor relapse in stage I-II rectal cancer and might be a useful biomarker for predicting recurrence in patients undergoing curative resection.

First-principles quantum Monte Carlo studies for prediction of double minima for positronic hydrogen molecular dianion.

We studied the positron (e+) interaction with the hydrogen molecular dianion H2 2- to form the positronic bound state of [H-; e+; H-] using the first-principles quantum Monte Carlo method combined with the multi-component molecular orbital one. H2 2- itself is unstable, but it was shown that such an unbound H2 2- may become stable by intermediating a positron and forming the positronic covalent bond of the [H-; e+; H-] system [J. Charry et al., Angew. Chem., Int. Ed. 57, 8859-8864 (2018)]. We newly found that [H-; e+; H-] has double minima containing another positronic bound state of [H2; Ps-]-like configuration with the positronium negative ion Ps- at the bond distance approximately equal to the equilibrium H2 molecule. Our multi-component variational Monte Carlo calculation and the multi-component configuration interaction one resulted in the positronic covalent bonded structure being the global minimum, whereas a more sophisticated multi-component diffusion Monte Carlo calculation clearly showed that the [H2; Ps-]-like structure at the short bond distance is energetically more stable than the positronic covalent bonded one. The relaxation due to interparticle correlation effects pertinent to Ps- (or Ps) formation is crucial for the formation of the Ps-A2-like structure for binding a positron to the non-polar negatively charged dihydrogen.

Involvement of Gßγ subunits of Gi protein coupled with S1P receptor on multivesicular endosomes in F-actin formation and cargo sorting into exosomes.

Exosomes play a critical role in cell-to-cell communication by delivering cargo molecules to recipient cells. However, the mechanism underlying the generation of the exosomal multivesicular endosome (MVE) is one of the mysteries in the field of endosome research. Although sphingolipid metabolites such as ceramide and sphingosine 1-phosphate (S1P) are known to play important roles in MVE formation and maturation, the detailed molecular mechanisms are still unclear. Here, we show that Rho family GTPases, including Cdc42 and Rac1, are constitutively activated on exosomal MVEs and are regulated by S1P signaling as measured by fluorescence resonance energy transfer (FRET)-based conformational changes. Moreover, we detected S1P signaling-induced filamentous actin (F-actin) formation. A selective inhibitor of Gßγ subunits, M119, strongly inhibited both F-actin formation on MVEs and cargo sorting into exosomal intralumenal vesicles of MVEs, both of which were fully rescued by the simultaneous expression of constitutively active Cdc42 and Rac1. Our results shed light on the mechanism underlying exosomal MVE maturation and inform the understanding of the physiological relevance of continuous activation of the S1P receptor and subsequent downstream G protein signaling to Gßγ subunits/Rho family GTPases-regulated F-actin formation on MVEs for cargo sorting into exosomal intralumenal vesicles.

Extracellular α-synuclein drives sphingosine 1-phosphate receptor subtype 1 out of lipid rafts, leading to impaired inhibitory G-protein signaling.

α-Synuclein (α-Syn)-positive intracytoplasmic inclusions, known as Lewy bodies, are thought to be involved in the pathogenesis of Lewy body diseases, such as Parkinson's disease (PD). Although growing evidence suggests that cell-to-cell transmission of α-Syn is associated with the progression of PD and that extracellular α-Syn promotes formation of inclusion bodies, its precise mechanism of action in the extracellular space remains unclear. Here, as indicated by both conventional fractionation techniques and FRET-based protein-protein interaction analysis, we demonstrate that extracellular α-Syn causes expulsion of sphingosine 1-phosphate receptor subtype 1 (S1P1R) from the lipid raft fractions. S1P1R regulates vesicular trafficking, and its expulsion involved α-Syn binding to membrane-surface gangliosides. Consequently, the S1P1R became refractory to S1P stimulation required for activating inhibitory G-protein (Gi) in the plasma membranes. Moreover, the extracellular α-Syn also induced uncoupling of the S1P1R on internal vesicles, resulting in the reduced amount of CD63 molecule (CD63) in the lumen of multivesicular endosomes, together with a decrease in CD63 in the released exosomes from α-Syn-treated cells. Furthermore, cholesterol-depleting agent-induced S1P1R expulsion from the rafts also resulted in S1P1R uncoupling. Taken together, these results suggest that extracellular α-Syn-induced expulsion of S1P1R from lipid rafts promotes the uncoupling of S1P1R from Gi, thereby blocking subsequent Gi signals, such as inhibition of cargo sorting into exosomal vesicles in multivesicular endosomes. These findings help shed additional light on PD pathogenesis.

Odd-Even Reactivity Variation Due to Dynamical Effects around the Roaming Saddle Points of the Reaction Between C n- Chain ( n = 2-8) and H2.

Unsaturated carbon cluster chains often have chemical properties depending on the cluster size. While carbon cluster cation chains show odd-even variation in the reactivity with hydrogen, the chemistry of the carbon anion chain has been poorly understood even for the bimolecular reaction with hydrogen. We present a systematic theoretical study based on transition state calculations and molecular dynamics trajectory simulations for the reaction of C n- ( n = 2-8) + H2. We show that carbon cluster chain anion also has an odd-even variation in reactivity where the even ones are more reactive. In addition, dynamics trajectory shows that while odd n only resulted in the C nH2- product with direct H insertion similar to the static reaction pathway, even n had a more complex product branching producing not only C nH2- but also C nH- + H and HC nH- with the roaming of an H atom. The flexibility of the carbon's valence electrons plays an important role to form different isomers of the double H adducts HC nH- and C nH2- from the roaming condition.

Benefits of laparoscopic surgery compared to open standard surgery for gastric carcinoma in elderly patients: propensity score-matching analysis.

BACKGROUND: Laparoscopic surgery is frequently performed, and laparoscopic gastrectomy (LG) is also widely performed for gastric cancer. Elderly population with gastric cancer has increased in East Asia, including in Japan. METHODS: We examined 1131 patients with gastric cancer who underwent laparoscopic and open standard surgeries (OG). A total of 921 patients of age < 75 years (non-E group) and 210 patients of age ≥ 75 years (E group) underwent surgery for gastric cancer. The mortality, morbidity, and prognosis of LG and OG were compared by propensity score-matched analysis. RESULTS: Mortality and morbidity in the E group were significantly higher than those in the non-E group (p < 0.05). Propensity score-matching revealed that the incidence of postoperative complications of grade ≥ 2 in the OG subgroup was significantly higher than that in the LG subgroup in the E group (p < 0.05). The overall survival rate of the LG subgroup was significantly higher than that of the OG subgroup in both the non-E and E groups (p < 0.05). The depth of tumor invasion, lymph node metastasis, and the number of dissected lymph nodes were dependent factors for survival in the non-E group, whereas the depth of tumor invasion was the only dependent factor for survival in the E group in the multivariate analysis. CONCLUSION: The survival rate of patients who underwent LG showed significantly good prognosis in both the non-E and E groups, although the E group patients who underwent OG subgroup showed higher severe complication incidences than those who underwent LG subgroup.

Reply to Correspondence on "Core Electron Topologies in Chemical Compounds: Case Study of Carbon versus Silicon".

In their Correspondence, von Szentpály, Schwarz, Stoll, and Werner claim that the main conclusions of our Communication previously published in this journal are based on computational artifacts and oversimplified models. We clarify the justification of our simple one-electron model to describe one-electron physics, and refute their criticism based on what they call "computational artifacts." We remind that our main conclusion on the crucial role of qualitative changes in core electron wavefunctions is evidenced not only by wavefunction topologies the complainants cling to, but also by several other physical observables, which remain unrefuted. Hence, the conclusions of our original Communication stand.