Trajectory of body mass index and height changes from childhood to adolescence: a nationwide birth cohort in Japan

To investigate the dynamics of body mass index (BMI) and height changes in childhood leading to obesity in adolescents. BMI Z-scores were calculated using the LMS (lambda-mu-sigma) method based on yearly height and weight information (age 1.5-15 years) from a nationwide Japanese birth cohort that started in 2001 (n = 26,711). We delineated the trajectories of BMI and height changes leading to obesity at age 15 years using mixed effect models. Children who became obese at the age of 15 years kept relatively high BMI z-scores through childhood for both genders, and had an increasing trend over time as opposed to the normal weight group, with an increasing slope during puberty. Early adiposity rebound was associated with overweight or obesity at the age of 15 years. Age at peak height velocity (APHV) occurred earlier in the obese/overweight group at age 15 years than in the normal weight group, and occurred later in the underweight group. Obese adolescents experienced early adiposity rebound timing and maintained a serial BMI z-score increase throughout childhood, with a greater slope at puberty. An earlier peak in height gain during puberty may have contributed to the observed patterns of BMI change

Beneficial effect of donor-specific blood transfusions (DST) on living-related kidney allograft survival.

The survival rate of 19 patients who underwent living-related kidney transplantation after donor-specific blood transfusions (DST) was compared with that of 32 historical controls receiving transplants without DST. The graft survival rate of the DST group was 82% after two and three years. The graft survival rate of the DST group was significantly better than the 53% rate after two years obtained with the 32 historical controls (p less than 0.05). We tested sera from 16 DST-treated recipients to study the beneficial effect of DST on kidney allograft survival using the mixed lymphocyte culture (MLC) serum inhibition test. The results demonstrated that MLC inhibitory factors were induced in the serum of the recipient after completion of DST. This inhibition of MLC was observed by treatment of responder lymphocytes with serum obtained three weeks after DST plus rabbit complement. The inhibitory effect was also specific for responder cells in anti-donor MLC. Regarding the correlation with rejection episodes, these MLC inhibitory factors were often observed in the non-rejection group (p less than 0.05). The data suggest that such factors may be anti-idiotypic antibodies and be associated with prolonged graft survival.</p

シンコウセイ ドウミャク コウカセイ ビョウヘン ニ タイシ ショウサイナ ビョウリ ソシキガクテキ ケントウ オ オコナイ エタ コウLp（a） ケッショウ ガッペイ 2ガタ トウニョウビョウ ノ 1レイ

We report a case of type 2 diabetes mellitus showing elevated plasma lipoprotein（a）［Lp（a）］levels with various atherosclerotic lesions. A 54-year-old woman diagnosed as having type 2 diabeteswas treated with oral antidiabetic drugs. She had various atherosclerotic lesions, includingcerebral infarction, occlusion of the middle carotid artery and myocardial infarction, along withdiabetes mellitus, hyperlipemia and hypertension and additionally showed a high level of serum Lp（a）. A high plasma level of Lp（a）is considered to be an independent risk factor for atherosclerosis,and it is associated with the development of cerebral infarction, occlusion of the middlecarotid artery and coronary atherosclerosis. Plasma Lp（a）level is predominantly determined bygenetic factors and is not affected by diet or drugs. Aspirin treatment（100 mg/day）lowered theplasma level of Lp（a）by 60%. Pathological findings of the vascular lesions showed that apolipoprotein（a）［apo（a）］, a major apoprotein component of Lp（a）, was deposited in the tunica media ofthe radial artery with rare atherosclerotic lesions and in the inner rim of the fibrous capsular regionwithin the plaque with a large lipid core of the carotid artery. This suggests that Lp（a）stimulatesthe transformation of vascular smooth muscle cells in the tunica media in the early stage of atherosclerosisand that it is associated with fragility of the atherosclerotic lesion in the progressive stage.Hence, plasma Lp（a）levels should be measured for diabetic patients with various atheroscleroticlesions, and aspirin may need to be given to those who have elevated plasma Lp（a）levels in orderto prevent the development of atherosclerotic complications

Succinate Increases in the Vitreous Fluid of Patients With Active Proliferative Diabetic Retinopathy

Purpose: To examine vitreous succinate levels from proliferative diabetic retinopathy (PDR) patients and ascertain their association with PDR activity. Design: Comparative case series. Methods: A total of 81 eyes of 72 PDR patients were divided into active PDR (22 eyes), quiescent PDR (21 eyes), and active PDR with intravitreal bevacizumab injection (38 eyes). Twenty epiretinal membrane (ERM) patients (21 eyes) served as controls. Results: Mean vitreous succinate levels were 1.27 μM in ERM and 2.20 μM in PDR, with the differences statistically significant (P = .03). When comparing mean vitreous succinate levels (active PDR: 3.32 μM; quiescent PDR: 1.02 μM; active PDR with intravitreal bevacizumab injection: 1.20 μM), significant differences were found between active and quiescent PDR (P < .01) and between active PDR and active PDR with intravitreal bevacizumab injection (P < .01). Even though succinate levels were low, retinopathy activities were very high in patients with active PDR with intravitreal bevacizumab injection. Mean vitreous vascular endothelial growth factor (VEGF) levels (active PDR: 1696 pg/mL; quiescent PDR: 110 pg/mL; active PDR with intravitreal bevacizumab injection: n.d.) were similar to previous reports. Mean vitreous erythropoietin levels (active PDR: 703 mIU/mL; quiescent PDR: 305 mIU/mL; active PDR with intravitreal bevacizumab injection: 1562 mIU/mL) suggested very high retinopathy activities in patients with active PDR with intravitreal bevacizumab injection. Conclusions: Succinate, like VEGF, may be an angiogenic factor that is induced by ischemia in PDR. Although succinate is reported to promote VEGF expression, VEGF inhibition decreases succinate. Thus, VEGF, via a positive feedback mechanism, may regulate succinate

QUALITY OF LIFE IN PATIENTS WITH DIABETES MELLITUS

We evaluated the quality of life (QOL) in 268 patients with diabetes mellitus (NIDDM, 250 cases; IDDM, 10 cases; and other type of diabetes, 8 cases) to determine which aspects were adversely affected by the disease. Information concerning life satisfaction, social activities, ability to work, sexual problems and physical symptoms was obtained from a 30-item questionnaire. Clinical characteristics including duration of diabetes, glycemic control, current treatment, obesity, hypertension, hyperlipidemia, macro- and microvascular complications were obtained from medical records. Diminished QOL was most pronounced in patients who had had a long duration of disease, required insulin therapy, and whose health was disturbed by cerebrovascular disease, end-stage renal disease, mono- and autonomic neuropathy. A significant difference in the subdimensional QOL score was noted in life satisfaction, social activities, ability to work, sexual problems and physical symptoms under these circumstances

Increased nerve growth factor expression in the synovial tissues of patients with rotator cuff tears

BACKGROUND: Rotator cuff tears (RCTs) are often associated with severe shoulder pain. Non-steroidal anti-inflammatory drugs, not recommended for long-term use, do not effectively manage RCT-induced pain, resulting in reduced quality of life. To improve management, a better understanding of the fundamental properties of RCT pain is needed. Here, we aimed to compare the expression levels of nerve growth factor (NGF) and cyclooxygenase-2 (COX-2) mRNA in the synovial tissues of patients with RCT-induced pain and patients with non-painful recurrent shoulder dislocation (RSD). METHODS: The study included 32 patients with RCT who underwent arthroscopic rotator cuff repair and 28 patients with non-painful RSD who underwent arthroscopic Bankart repair. Synovial tissue samples were harvested from subacromial bursa and rotator interval of RCT patients and from the rotator interval of RSD patients. Samples were analyzed quantitatively expression levels for NGF and COX2 mRNA and NGF protein. RESULTS: NGF mRNA and protein levels were significantly higher in the rotator interval of RCT patients than in the rotator interval of RSD patients (p = 0.0017, p = 0.012, respectively), while COX2 mRNA levels did not differ significantly between the two patient groups. In RCT patients, COX2 mRNA was more highly expressed in the rotator interval than in the subacromial bursa (p = 0.038), whereas the mRNA and protein levels of NGF did not differ between the two tissues. The expression of NGF mRNA in the synovium of the rotator interval was significantly correlated with the numeric rating scale of pain (ρ = 0.38, p = 0.004). CONCLUSION: NGF mRNA and protein levels were elevated in patients with painful RCT compared with those in patients with non-painful RSD, whereas COX-2 levels were comparable in the two patient groups. These findings provide insights into novel potential strategies for clinical management of RCT

Relationships between Composition of Major Fatty Acids and Fat Distribution and Insulin Resistance in Japanese

Objective. The aim of this study was to evaluate the relationships between the composition of free fatty acids (FFAs) and metabolic parameters, including body fat distribution, in Japanese. Methods. The study subjects were 111 Japanese patients (54 males, 57 females). Metabolic parameters and visceral and subcutaneous fat areas as determined by CT scanning at the umbilical level were measured. Glucose tolerance test (GTT) was performed by administering 75 g glucose orally. Results. The percentage of linoleic acid (C18:2), the greatest constituent among FFAs, was negatively correlated with visceral fat area (r = −0 411, p &lt; 0 0001), fasting glucose (r = −0 330, p &lt; 0 0001), HbA1c (r = −0 231, p = 0 0146), and systolic blood pressure (r = −0 224, p = 0 0184). Linoleic acid percentage was also significantly negatively correlated with HOMA-IR (r = −0 416, p &lt; 0 0001) by simple correlation. Based on the findings of OGTT, the 111 subjects were classified into three groups: 33 with normal glucose tolerance, 71 with impaired glucose tolerance (IGT), and 7 diabetic subjects. The percentage of serum linoleic acid in diabetic subjects was significantly lower than that in normal subjects. Conclusion. We conclude that serum linoleic acid level is negatively correlated with the accumulation of visceral fat in relation to a reduction of insulin resistance in Japanese subjects

Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype

Cellular senescence, a state of irreversible cell-cycle arrest caused by a variety of cellular stresses, is critically involved in age-related tissue dysfunction in various organs. However, the features of cells in the central nervous system that undergo senescence and their role in neural impairment are not well understood as yet. Here, through comprehensive investigations utilising single-cell transcriptome analysis and various mouse models, we show that microglia, particularly in the white matter, undergo cellular senescence in the brain and spinal cord during ageing and in disease models involving demyelination. Microglial senescence is predominantly detected in disease-associated microglia, which appear in ageing and neurodegenerative diseases. We also find that commensal bacteria promote the accumulation of senescent microglia and disease-associated microglia during ageing. Furthermore, knockout of p16 INK4a, a key senescence inducer, ameliorates the neuroinflammatory phenotype in damaged spinal cords in mice. These results advance our understanding of the role of cellular senescence in the central nervous system and open up possibilities for the treatment of age-related neural disorders.Matsudaira T., Nakano S., Konishi Y., et al. Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype. Communications Biology 6, 665 (2023); https://doi.org/10.1038/s42003-023-05027-2

Compressed Amplatzer Vascular Plug II Embolization of the Left Subclavian Artery for Thoracic Endovascular Aortic Repair is Efficient and Safety Method Comparable to Conventional Coil Embolization

[Background] Left subclavian artery (LSA) embolization is occasionally required to prevent type II endoleak in the thoracic endovascular aortic repair (TEVAR) procedure. This is a retrospective study comparing compressed Amplatzer Vascular Plug II embolization (CAE) and conventional coil embolization (CCE) in preventing retrograde flow into the aneurysmal sac through the LSA after TEVAR. [Methods] We retrospectively reviewed the records of patients who underwent CAE or CCE of the LSA during TEVAR from June 2013 to March 2016 in our hospital. The efficacy, safety and cost of each method were compared between two groups. [Results] Thirty patients underwent LSA embolization during TEVAR. Six CCEs in 6 patients were performed from June 2013 to November 2013, while twenty-four CAEs in 24 patients were performed from December 2013 to March 2016. Technical success was achieved in all patients in both groups. No embolization-related complications or type II endoleaks from LSA were recorded during the follow-up period in all patients. In both groups, all embolic materials were detected in the proximal portion of the LSA from the LSA orifice to the vertebral artery origin and no vertebral artery occlusions were detected. The mean compression ratio of AVP II was 58 ± 5.9% of predicted length of standard procedure. In the CAE group, one AVP II was sufficient to achieve complete LSA occlusion in all patients. On the other hand, multiple coils (10.2 ± 2.7) were used in the CCE group (P < .01), resulting in a significantly lower cost incurred in the CAE group (CAE: 129,000 JPY vs. CCE: 639,600 ± 140,060 JPY; P < .01). [Conclusion] The CAE is a useful and cost-effective procedure for TEVAR-related LSA embolization

Unravelling nicotinic receptor and ligand features underlying neonicotinoid knockdown actions on the malaria vector mosquito Anopheles gambiae

With the spread of resistance to long-established insecticides targeting Anopheles malaria vectors, understanding the actions of compounds newly identified for vector control is essential. With new commercial vector-control products containing neonicotinoids under development, we investigate the actions of 6 neonicotinoids (imidacloprid, thiacloprid, clothianidin, dinotefuran, nitenpyram and acetamiprid) on 13 Anopheles gambiae nicotinic acetylcholine receptor (nAChR) subtypes produced by expression of combinations of the Agα1, Agα2, Agα3, Agα8 and Agβ1 subunits in Xenopus laevis oocytes, the Drosophila melanogaster orthologues of which we have previously shown to be important in neonicotinoid actions. The presence of the Agα2 subunit reduces neonicotinoid affinity for the mosquito nAChRs, whereas the Agα3 subunit increases it. Crystal structures of the acetylcholine binding protein (AChBP), an established surrogate for the ligand-binding domain, with dinotefuran bound, shows a unique target site interaction through hydrogen bond formation and CH-N interaction at the tetrahydrofuran ring. This is of interest as dinotefuran is also under trial as the toxic element in baited traps. Multiple regression analyses show a correlation between the efficacy of neonicotinoids for the Agα1/Agα2/Agα8/Agβ1 nAChR, their hydrophobicity and their rate of knockdown of adult female An. gambiae, providing new insights into neonicotinoid features important for malaria vector control