[Application and value of intravascular ultrasound for excimer laser ablation combined with drug-coated balloon in the treatment of lower limb arteriosclerotic obliterans].

Objective: To examine the value of intravascular ultrasound (IVUS) for excimer laser ablation (ELA) combined with drug-coated balloon (DCB) in treating lower limb arteriosclerotic obliterans (ASO). Methods: As a prospective case series study, patients who underwent ELA combined with DCB for lower limb ASO with the guidance of IVUS from September 2021 to March 2022 at Department of Vascular Surgery, Zhongshan Hospital, Fudan University were enrolled prospectively. Lesion characteristics, procedure-related outcomes and complications were collected. The therapy outcomes were compared with baseline data by paired t test. Results: There were 8 males and 2 females, aged (72.0±5.9) years (range: 61 to 81 years). Of all the 11 lesions, there were 8 lesions in superficial femoral artery and 3 in popliteal artery. The lesion length was (7.0±2.4) cm (range: 3.2 to 9.8 cm). There were 4 chronic totally occlusion and 7 severe stenosis. All patients underwent the operation successfully. The technical success rate was 10/11. Bailout stenting was performed in one lesion because of flow-limiting dissection. Four lesions were grade 3 to 4 in peripheral artery calcium score system, and 9 lesions with calcification arc≥180°. Larger diameter drug-coated balloons were selected in 5 lesions after measurement of intravascular ultrasound. The follow-up time was (6.0±1.9) months (range: 3 to 9 months). The ankle-brachial index of the patient was significantly improved immediately after surgery (0.97±0.13 vs. 0.48±0.18, t=-7.60, P<0.01) and at 3 months after surgery (0.95±0.12 vs. 0.48±0.18, t=-7.17, P<0.01). The 3-month primary patency rate was 11/11, the target lesion reintervention was 0 and ulcer healing rate was 3/4. Conclusion: IVUS assisted ELA in the treatment of lower limb artery lesions is safe and effective in early stage.

[Application value of excimer laser ablation combined with drug-coated balloon in non-stent atherosclerotic lesions of lower extremity arteries].

Objective: To examine the effect of excimer laser ablation (ELA) combining with drug-coated balloon (DCB) for atherosclerotic lesions in no-stenting zones (NSZ) of the lower extremity. Methods: From June 2019 to December 2021, 46 patients who underwent ELA combining with DCB in lesions of NSZ at Zhongshan Hospital, Fudan University and Jinshan Hospital, Fudan University were retrospectively enrolled, including 29 males and 17 females. The age was (72.5±11.7) years (range: 42 to 93 years). Among them, 44 lesions (95.7%, 44/46) were in popliteal artery and 2 lesions (4.3%, 2/46) were in common femoral artery. Chronic total occlusion (CTO) was observed in 31 patients (76.4%, 31/46), and stenotic lesions were observed in 15 patients (32.6%, 15/46). The length of lesions was (7.3±2.7) cm (range: 3.0 to 13.2 cm). Patients were followed at 6, 12 months after surgery and every year thereafter, and they underwent Doppler and CT angiography examination at each follow-up point. The primary endpoint was primary patency. The secondary endpoints included major amputation-free survival (MAFS) rate, technical success, bailout stent, ankle-brachial index (ABI), target lesion reintervention (TLR). Student t test was applied to compare the difference between ABI of 6 or 12 months after surgery and the baseline. Primary patency, freedom from TLR, and MAFS rate were calculated by Kaplan-Meier method. Results: The technical success rate was 91.3% (42/46). The rate of procedure-related complication was 6.5% (3/46), and all the complications were distal embolization. The rate of flow-limiting dissection was 8.7% (4/46). ABI was significantly increased at 6 and 12 months compared to preoperatively (0.90±0.10 vs. 0.42±0.10, t=-4.48, P<0.01; 0.87±0.12 vs. 0.42±0.10, t=-5.21, P<0.01). The follow-up time[M(IQR)] was 22.5 (8.8) months (range: 6 to 32 months). TLR was performed in 4 patients (4/46, 8.7%). The 2-year primary patency was 86.2% (95%CI: 71.8% to 93.5%). The 2-year freedom from TLR and MAFS rate were 90.7% (95%CI: 77.0% to 96.4%) and 97.8% (95%CI: 85.6% to 99.7%), respectively. Conclusion: ELA combining with DCB can be applied to treat atherosclerotic lesions in NSZ.

[Application and value of excimer laser ablation in the treatment of lower limb atherosclerotic obliterans].

Objective: To evaluate the results of excimer laser ablation (ELA) in the treatment of lower limb atherosclerotic obliterans (ASO). Methods: From June 2019 to March 2020, patients who underwent ELA combined with drug-coated balloon (DCB) for lower limb atherosclerotic obliterans (ASO) were enrolled. Demographics, lesion characteristics, procedure-related outcomes and complications were collected and analyzed. Results: Thirty patients were enrolled, including 21 males and 9 females. The mean age was (76.5±10.5) years. The mean lesion length was (11.7±6.4) cm. A total of 41 lesions, including in-stent restenosis (ISR) in 12 (29.3%), chronic totally occlusion (CTO) at initial treatment in 24 (58.5%), and severe stenosis in 5 (12.2%) patients. Sixteen (51.6%) patients were classified as Peripheral Arterial Calcium Scoring System (PACSS) category 4. The technical success rate was 93.5%. Incidence of distal embolization and bailout stenting was 12.9% and 6.5%, respectively. The mean follow-up time was (6.6±3.0) months. Ankle-brachial index (ABI) was significantly increased from 0.43(0.32,0.55) preoperatively to 0.91(0.87,1.01) postoperatively (Z=-5.43, P<0.01) and 0.82(0.73,1.02) (Z=-3.99, P<0.01) three months after surgery. The 3-month major-amputation free survival rate was 96.7%, primary patency rate was 100%, the target lesion reintervention (TLR) rate was 0 and ulcer healing rate was 76.9%. Conclusion: Debulking of ELA is feasible and effective for both ISR and CTO at initial treatment, providing a new option for DCB preparation and reducing stent implantation.

[Debulking strategy of endovascular treatment for lower extremity artery lesions].

Objective: To explore the debulking strategy of lower extremity artery lesions. Methods: Retrospectively analyzed the clinical data of 101 patients underwent debulking therapy at Department of Vascular Surgery,Zhongshan Hospital,Fudan University from June 2019 to June 2020.There were 74 males and 27 females,aged (73.2±11.7)years (range:35 to 93 years).There were 31 cases in Rutherford class 3,39 cases in class 4 and 31 cases in class 5. Hypertension occurred in 72 patients. One hundred and forty lesions were treated in 101 patients. Among them, there were 13 lesions(9.3%) in iliac artery,72 lesions(51.4%) in superficial femoral artery,41 (29.3%) lesions in popliteal artery,10 lesions(7.1%) in tibiofibular trunk,and 4 lesions(2.9%) in below the knee artery.Percutaneous mechanical thrombectomy (PMT) was mainly used in acute thrombosis,excimer laser ablation (ELA) was mainly used for chronic in-stent restenosis and chronic stenosis or totally occlusive lesions,while directional atherectomy (DA) was mainly used for short calcified lesions. Results: All of the patients underwent debulking therapy. Eighty-two lesions(58.6%,82/140) were treated by PMT, 56 (40.0%,56/140) were treated by ELA,and 2 (1.4%,2/140) were treated by DA.The ankle-brachial index of the patient was 0.44±0.19 before surgery, 0.87±0.17 immediately after surgery (t=-16.26, P<0.01), and 0.81±0.20 at 6 months after surgery(t=-14.67,P<0.01),and 0.79±0.15 (t=-14.12,P<0.01) at 12 months after surgery. At 12 months,the primary patency was 86.1% (87/101),mortality was 5.0% (5/101), freedom from major-amputation survival rate was 93.1% (94/101),and target lesion reintervention rate was 9.9% (10/101). Conclusions: Debulking is feasible and effective to eliminate the arterial contents and maximize the acquisition of lumen.Selection of suitable debulking methods for different segments and lesions would be helpful to improve the technical success and obtain satisfactory results.

[Influence of thread shapes of custommade root-analogue implants on stress distribution of peri-implant bone: A three-dimensional finite element analysis].

OBJECTIVE: To explore the effects from the thread shapes of custom-made root-analogue implant (RAI) on distributions of von Mises stress around the peri-implant bone. METHODS: Five one-stage RAI three-dimensional finite element (FE) models with different thread shapes (V-shaped design, square design, buttress design, reverse buttress design and none thread design) and congruent bone were created through reverse engineering technology. The data of the five models were imported into the FE analysis software to calculate. A force of 100 N was applied parallelly and of 45° to the implant axis respectively. Analysis was performed to evaluate the von Mises stress distributions at the peri-implant regions with the help of the Ansys 16 software. RESULTS: The von Mises stresses distributed mostly at the implant cervical regions and the tip ends of the threads on the cortical bone under oblique loading, while on the cancellous bone, the stresses concentrated mostly on the implant lateral cervical regions, the tip ends of the threads and the apical regions. When under vertical loading, the von Mises stresses distributed mostly at the implant cervical regions on the cortical bone while at the tip ends of the threads and the lateral apical regions on the cancellous bone. The von Mises stresses were better distributed on the thread groups under both kinds of loadings compared with no thread design. But there was no obvious difference among the different thread groups. The concentrations of the von Mises stresses on the cancellous bone in the thread groups were mostly at the tip ends of the threads while less in the apical area. The von Mises stresses were better distributed on the cancellous bone on the other three thread designs than on square design. CONCLUSION: Thread designs are advocated for the reason that adding thread designs to the RAI standard design will have a positive effect on stress distributions at the peri-implant regions and it will reduce the concentrations of von Mises stresses on the cortical bone. From the standpoint of the stress distribution, V-shaped design, buttress design and reverse buttress design are more suitable for RAI than square design. There is no difference of the distributions of the von Mises stresses in the RAI between different thread designs.

[Optimal timing of endovascular treatment for uncomplicated Stanford type B aortic dissection].

Stanford type B aortic dissection (TBAD) is an acute and life-threatening disease. The treatment of TBAD used to be depended on whether it is complicated. The therapeutic guidelines recommend thoracic endovascular aortic repair (TEVAR) as first-line treatment for patients with acute complicated TBAD, while recommend best medical therapy for patients with acute uncomplicated TBAD (UTBAD). However, the latest studies suggest that patients with UTBAD also should be treated with pre-emptive TEVAR, which can significantly improve aortic remodeling and clinical outcome. Considering improvement of aortic remodeling and prevention of severe complications, the best timing of pre-emptive TEVAR may be 14-90 days after the onset of TBAD (subacute phase). The other main issue is identifying which patients with UTBAD should undergo pre-emptive TEVAR. Several risk factors including imaging, clinical and laboratory parameters have been shown to be associated with aortic-related events in patients with UTBAD. Among imaging finding, the diameters of aortic or false lumen, the status of true or false lumen, the size or number of entry tears have identified to be as predictors of adverse aortic events in patients with UTBAD.

Leukemia inhibitory factor (LIF) potentiates antinociception activity and inhibits tolerance induction of opioids.

BACKGROUND: The efficacy of opioids typically decreases after long-term use owing to the development of tolerance. Glial activation and the upregulation of proinflammatory cytokines are related to the induction of tolerance. We investigated the effect of leukemia inhibitory factor (LIF) on morphine analgesia and tolerance. METHODS: LIF concentrations in rat spinal cords were measured by polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) after morphine administration. LIF distribution was examined using confocal microscopy. To evaluate the effects of LIF on morphine analgesia and tolerance, LIF was intrathecally administered 30 min before morphine injection. The analgesic effect of morphine was evaluated by measuring tail-flick latency. Human LIF concentrations from the cerebrospinal fluid (CSF) of opioid tolerant patients were also determined by specific ELISA. RESULTS: Chronic morphine administration upregulated LIF concentrations in rat spinal cords. Intrathecal injection of LIF potentiated the analgesic action of morphine. Patch clamp recording of spinal cord slices showed that LIF enhanced DAMGO ([D-Ala2, N-MePhe4, Gly-ol]-enkephalin)-induced outward potassium current. The development of tolerance was markedly suppressed by exogenous LIF, whereas neutralizing the endogenously released LIF with anti-LIF antibodies accelerated the tolerance induction. Moreover, LIF concentrations in the CSF of opioid-tolerant patients were higher than those in the opioid-naive controls. CONCLUSIONS: Intrathecal administration of LIF potentiated morphine antinociceptive activity and attenuated the development of morphine tolerance. Upregulation of endogenously released LIF by long-term use of opioids might counterbalance the tolerance induction effects of other proinflammatory cytokines. LIF might be a novel drug candidate for inhibiting opioid tolerance induction.

Fatigue life enhancement of NiTi rotary endodontic instruments by progressive reciprocating operation.

AIM: To evaluate the effect of reciprocating amplitude and progressive angular increment on fatigue life enhancement of NiTi rotary endodontic instruments. METHODOLOGY: ProTaper F2 instruments were operated in steel artificial canals with both stationary reciprocating (SR) and progressive reciprocating (PR) motions. The SR motions involved symmetric to and fro reciprocation of ± 180(o) , ± 135(o) , ± 90(o) , ± 60(o) and ± 45(o) . The PR motions were ± 45(o) stationary motion superimposed with angular increments of 7(o) , 11(o) , 22.5(o) or 31(o) whenever an instrument completed 1, 10 or 30 reciprocating cycles (rc). The fatigue lives were compared with those under continuous rotation (CR) and a reciprocating operation with a forward 144(o) and backward 72(o) motion proposed by Yared (2008). The statistical significance of these operating modes on fatigue life was examined using one way anova and post hoc Tukey's tests at P = 0.05. Fractographic analysis was also applied to probe the fracture mechanisms of different rotation motions. RESULTS: Fatigue life increased with decreasing reciprocating amplitude. Operating in the SR increased fatigue life by 355% over that in the CR. Except for the 22.5(o) increment, all PR motions yielded longer fatigue lives than the SR motion. A progressive reciprocating operation with a ± 45(o) reciprocating amplitude and a + 7(o) progressive angular increment every 10 reciprocating cycles (± 45(o) /10rc/+7(o) ) increased fatigue life by 990% over that in the CR motion. In terms of life enhancement over the CR motion, the larger the curvature the less are the differences between different movements. Single crack initiation sites were found in the CR and SR motions, while three crack initiation sites were typical in the ± 45(o) /10rc/+7(o) motion. CONCLUSIONS: Fatigue life increased with decreasing reciprocating amplitude in stationary reciprocation. A progressive reciprocating operation with ± 45(o) /10rc/+7(o) motion led to significant fatigue life enhancement and multiple fatigue crack initiation in NiTi endodontic instruments.

Streptococcus agalactiae infective endocarditis with large vegetation in a patient with underlying protein S deficiency.

We present a case of a patient with underlying protein S deficiency who suffered from infective endocarditis with a large anterior mitral leaflet (AML) mass of approximately 4.5 cm in length. Intraoperative transesophageal echocardiography (TEE) revealed the mass at the AML base and a rupture of the posterior mitral leaflet chordae tendinae. The vegetation's large size may have been caused by one or more of three factors: location, underlying disease, and the microorganism causing infection. Patients with protein S deficiency are prone to thromboembolic events during cardiac surgery. Infective endocarditis caused by Streptococcus agalactiae usually has a poor prognosis, and, thus, early surgery is recommended.

Role of MYH9 and APOL1 in African and non-African populations with lupus nephritis.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and organ damage. Lupus nephritis (LN) is one of the most severe manifestations of SLE. Multiple studies reported associations between renal diseases and variants in the non-muscle myosin heavy chain 9 (MYH9) and the neighboring apolipoprotein L 1 (APOL1) genes. We evaluated 167 variants spanning MYH9 for association with LN in a multiethnic sample. The two previously identified risk variants in APOL1 were also tested for association with LN in European-Americans (EAs) (N = 579) and African-Americans (AAs) (N = 407). Multiple peaks of association exceeding a Bonferroni corrected P-value of P < 2.03 × 10(-3) were observed between LN and MYH9 in EAs (N = 4620), with the most pronounced association at rs2157257 (P = 4.7 × 10(-4), odds ratio (OR) = 1.205). A modest effect with MYH9 was also detected in Gullah (rs8136069, P = 0.0019, OR = 2.304). No association between LN and MYH9 was found in AAs, Asians, Amerindians or Hispanics. This study provides the first investigation of MYH9 in LN in non-Africans and of APOL1 in LN in any population, and presents novel insight into the potential role of MYH9 in LN in EAs.

Prevalence and molecular characterization of abnormal hemoglobin in eastern Guangdong of southern China.

Abnormal hemoglobins (Hbs) are the most commonly inherited disorders in humans. Their frequency and types change considerably with geographic location and ethnic group. To investigate the molecular epidemiological characterization of abnormal Hbs in eastern Guangdong of southern China, a total of 11,450 'healthy' subjects were subjected to hemoglobin electrophoresis screening. Samples of EDTA-K(2) blood with abnormal Hbs were analyzed by CELL-DYN1700 blood analyzer; thalassemia genotypes and Hb E variant were identified by gap-PCR and/or reverse dot blot (RDB). The genotypes of Hb variants were detected by PCR and sequencing. The incidence of abnormal Hbs was 0.358%(41/11,450) in Chaozhou, including 12.2% (5/41) Hb J, 4.9% (2/41) Hb K, 9.7% (4/41) Hb Q, 31.7% (13/41) Hb G/D and 41.5% (17/41) Hb E. Eight types of Hb variants were found, including 3 cases of Hb J-Bangkok, 2 cases of Hb J-Wenchang-Wuming, 2 cases of Hb New York, 4 cases of Hb Q-Thailand, 5 cases of Hb G-Waimanalo, 4 cases of Hb Ottawa, 4 cases of Hb G-Chinese and 17 cases of Hb E. In comparison with other areas of Guangdong, Chaozhou had a different pattern of abnormal Hbs with a high prevalence of Hb G/D. This study describes the prevalence and molecular characterization of abnormal Hbs in eastern Guangdong.

The development of iron-free partially stabilized cement for use as dental root-end filling material.

AIM: To determine the effect of increasing the proportion of zinc on partially stabilized cement (PSC) produced using a one-step sol gel process. METHODOLOGY: A one-step sol-gel process of Portland cement-based PSC with Zn was synthesized by replacing iron nitrate. The crystalline phases of the PSC-Zn powder were analysed by using X-ray diffraction (XRD). The experimental groups [i.e., MTA, PSC-Fe (control), PSC with 1% Zn, PSC with 3% Zn, and PSC with 5% Zn] were immersed in simulated body fluid for 3 h, 1 and 3 days to evaluate the hydration product formation. The microstructure and surface morphology were analysed using scanning electron microscopy (SEM). Initial and final setting times of the materials were determined using an ASTM Vicat needle testing machine. To evaluate the cytotoxicity of PSC-Zn system, primary osteoblasts cell lines were used. RESULTS: The addition of increased weight percentages of Zn, resulted in a more unstable phase which favoured the formation of a monoclinic structure of C3 S with an increased hydration reaction of PSC and reduced setting time. The cytotoxicity testing of PSC with Zn revealed that the material was not toxic. CONCLUSIONS: The newly synthesized PSC-Zn material had short setting time and was biocompatible.

Quantification of bone marrow interstitial pH and calcium concentration by intravital ratiometric imaging.

The fate of hematopoietic stem cells (HSCs) can be directed by microenvironmental factors including extracellular calcium ion concentration ([Ca2+]e), but the local [Ca2+]e around individual HSCs in vivo remains unknown. Here we develop intravital ratiometric analyses to quantify the absolute pH and [Ca2+]e in the mouse calvarial bone marrow, taking into account the pH sensitivity of the calcium probe and the wavelength-dependent optical loss through bone. Unexpectedly, the mean [Ca2+]e in the bone marrow (1.0 ± 0.54 mM) is not significantly different from the blood serum, but the HSCs are found in locations with elevated local [Ca2+]e (1.5 ± 0.57 mM). With aging, a significant increase in [Ca2+]e is found in M-type cavities that exclusively support clonal expansion of activated HSCs. This work thus establishes a tool to investigate [Ca2+]e and pH in the HSC niche with high spatial resolution and can be broadly applied to other tissue types.

Highly efficient multipotent differentiation of human periodontal ligament fibroblasts induced by combined BMP4 and hTERT gene transfer.

Because periodontal ligament (PDL) cells are reported to contain progenitor or stem cell populations, they are considered a beneficial cell source for clinical periodontal regeneration. Both bone morphogenetic protein 4 (BMP4) and human telomerase reverse transcriptase (hTERT) have essential roles in the modulation of stem cell properties. In this study we report for the first time that the combined ectopic expression of BMP4 and hTERT significantly enhanced the multipotent differentiation efficiency and capacity of human PDL fibroblasts (PFs), as shown by osteogenic, adipogenic and neurogenic differentiation in vitro, and cementum/PDL-like tissue regeneration in vivo. These findings may be attributed, at least in part, to the original upregulation of important stem cell markers, such as scleraxis, Stro-1 and CD146, and the extremely lowered threshold for BMP concentration to activate BMP signaling by enhanced basal phosphorylation levels of Smad 1/5/8. In addition, the significantly reduced expression levels of CD146 and CD90 with the presence of Noggin confirms the direct effect of BMP4 on the stem cell-like phenotype of genetically modified PF cells (BT-PFs). Furthermore, BT-PFs exhibited a high neural differentiation capacity (>75%). After transplantation into NOD/SCID mice, genetically modified-PFs generated cementum/PDL-like structures on the surface of the carrier. The multipotency of these modified cells potentially provides an attractive source of stem cells for therapeutic purposes and regenerative medicine.

Correlation between the flow pattern of the circle of Willis and segmental perfusion asymmetry after carotid artery revascularization.

BACKGROUND: To correlate cerebral perfusion and flow patterns after carotid artery revascularization within the circle of Willis (CoW). METHODS: Sixty-five patients (male/female ratio: 38/27; mean age: 63.2±8.4years; range: 44-82years) with symptomatic carotid artery stenosis underwent magnetic resonance (MR) angiography and perfusion imaging prior to and after carotid artery stenting (CAS). Regions of interest (ROIs) on the MR perfusion maps included the corona radiata (CR), centrum semiovale (CSO), occipital region (O), and basal ganglia region (BA) in both stented and non-stented hemispheres. The non-stented hemisphere was used as internal control. RESULTS: Subjects were assigned to the altered CoW group (N=31) vs. the static CoW group (N=34). Thirty-one subjects (47.6%) had an altered flow pattern in the CoW after CAS, and thirty-four (52.4%) retained a static CoW configuration. Relative cerebral blood volume (rCBV) interhemispheric index correlated with CoW morphologic alterations after carotid stenting. Altered CoW group had a higher regional interhemispheric index of rCBV in the CR (1.23±0.15 vs. 0.87±0.13; P=0.03) and basal ganglia (1.25±0.12 vs. 0.91±0.11; P=0.03) compared to the static group. CONCLUSIONS: An association between the regional cerebral blood volume (rCBV) interhemispheric asymmetry and CoW collateralization was observed. In addition, the CR, rather than CSO, was found to have topographic significance.

Linking Stage-Specific Plasma Biomarkers to Gray Matter Atrophy in Parkinson Disease.

BACKGROUND AND PURPOSE: The shortcomings of synucleinopathy-based Parkinson disease staging highlight the need for systematic clinicopathologic elucidation and biomarkers. In this study, we investigated associations of proteinopathy and inflammation markers with changes in gray matter volume that accompany Parkinson disease progression. MATERIALS AND METHODS: We prospectively enrolled 42 patients with idiopathic Parkinson disease, subdivided into early-/late-stage groups and 27 healthy controls. Parkinson disease severity and participants' functional and cognitive performance were evaluated. Peripheral plasma α-synuclein, ß-amyloid42, and tau were quantified with immunomagnetic reduction assays, and nuclear DNA by polymerase chain reaction, and regional gray matter volumes were determined by MR imaging. Statistical tests identified stage-specific biomarkers and gray matter volume patterns in the early-stage Parkinson disease, late-stage Parkinson disease, and control groups. Correlations between gray matter volume atrophy, plasma biomarkers, Parkinson disease severity, and cognitive performance were analyzed. RESULTS: Patients with Parkinson disease had significantly elevated α-synuclein, tau, and ß-amyloid42 levels compared with controls; nuclear DNA levels were similar in early-stage Parkinson disease and controls, but higher in late-stage Parkinson disease (all P < .01). We identified 3 stage-specific gray matter volume atrophy patterns: 1) control > early-stage Parkinson disease = late-stage Parkinson disease: right midfrontal, left lingual, and fusiform gyri, left hippocampus, and cerebellum; 2) control > early-stage Parkinson disease > late-stage Parkinson disease: precentral, postcentral, parahippocampal, left superior-temporal, right temporal, right superior-frontal, and left cingulate gyri, occipital lobe, and bilateral parts of the cerebellum; 3) control = early-stage Parkinson disease > late-stage Parkinson disease: left midfrontal, superior-frontal and temporal, amygdala, and posterior cingulate gyri, caudate nucleus, and putamen. We discovered stage-specific correlations among proteinopathy, inflammation makers, topographic gray matter volume patterns, and cognitive performance that accompanied Parkinson disease progression. CONCLUSIONS: Identifying associations linking peripheral plasma biomarkers, gray matter volume, and clinical status in Parkinson disease may facilitate earlier diagnosis and improve prognostic accuracy.

Physio-Cognitive Decline Syndrome as the Phenotype and Treatment Target of Unhealthy Aging.

In this era of unprecedented longevity, healthy aging is an important public health priority. Avoiding or shortening the period of disability or dementia before death is critical to achieving the defining objectives of healthy aging, namely to develop and maintain functional capabilities that enable wellbeing in older age. The first step is to identify people who are at risk and then to implement effective primary interventions. Geriatricians have identified a distinct clinical phenotype of concurrent physical frailty and cognitive impairment, which predicts high risk of incident dementia and disability and is potentially reversible. Differing operational definitions for this phenotype include "cognitive frailty", "motoric cognitive risk syndrome" and the recently proposed "physio-cognitive decline syndrome (PCDS)". PCDS is defined as concurrent mobility impairment no disability (MIND: slow gait or/and weak handgrip) and cognitive impairment no dementia (CIND: ≥1.5 SD below the mean for age-, sex-, and education-matched norms in any cognitive domain but without dementia). By these criteria, PCDS has a prevalence of 10-15% among community-dwelling older persons without dementia or disability, who are at increased risk for incident disability (HR 3.9, 95% CI 3.0-5.1), incident dementia (HR 3.4, 95% CI 2.4-5.0) and all-cause mortality (HR 6.7, 95% CI 1.8-26.1). Moreover, PCDS is associated with characteristic neuroanatomic changes in the cerebellum and hippocampus, and their neurocircuitry, which are distinct from neuroimaging features in normal aging and common dementia syndromes. Basic research and longitudinal clinical studies also implicate a hypothetical muscle-brain axis in the pathoetiology of PCDS. Most important, community-dwelling elders with PCDS who participated in a multidomain intervention had significant improvements in global cognitive function, and especially in the subdomains of naming and concentration. Our proposed operational definition of PCDS successfully identifies an appreciable population of at-risk older people, establishes a distinct phenotype with an apparently unique pathoetiology, and is potentially reversible. We now need further studies to elucidate the pathophysiology of PCDS, to validate neuroimaging features and muscle-secreted microRNA biomarkers, and to evaluate the effectiveness of sustained multidomain interventions.

Insect form vision as one potential shaping force of spider web decoration design.

Properties of prey sensory systems are important factors shaping the design of signals generated by organisms exploiting them. In this study we assessed how prey sensory preference affected the exploiter signal design by investigating the evolutionary relationship and relative attractiveness of linear and cruciate form web decorations built by Argiope spiders. Because insects have an innate preference for bilaterally symmetrical patterns, we hypothesized that cruciate form decorations were evolved from linear form due to their higher visual attractiveness to insects. We first reconstructed a molecular phylogeny of the Asian members of the genus Argiope using mitochondrial markers to infer the evolutionary relationship of two decoration forms. Results of ancestral character state reconstruction showed that the linear form was ancestral and the cruciate form derived. To evaluate the luring effectiveness of two decoration forms, we performed field experiments in which the number and orientation of decoration bands were manipulated. Decoration bands arranged in a cruciate form were significantly more attractive to insects than those arranged in a linear form, no matter whether they were composed of silks or dummies. Moreover, dummy decoration bands arranged in a cruciate form attracted significantly more insects than those arranged in a vertical/horizontal form. Such results suggest that pollinator insects' innate preference for certain bilateral or radial symmetrical patterns might be one of the driving forces shaping the arrangement pattern of spider web decorations.