A 160-GHz frequency-translation PLL with tuning range from 156.4 GHz to 159.2 GHz is presented. Sub-THz 1/9 prescaler is replaced by a 3rd harmonic mixer incorporating a frequency tripler for ...frequency down conversion. A transformer-based VCO is utilized to alleviate capacitive and resistive load associated with varactor and succeeding buffer stages. Frequency acquisition is assisted by received signal strength indicator (RSSI) for automatic frequency sweeping and fast locking. Fabricated in 65 nm CMOS technology, the chip size is 0.92 mm 2 . The PLL locking time is less than 3 μs. This chip drains 24 mW from a 1.2 V power supply.
We successfully demonstrate the first solid-state sensor to have reliable responses to breath ammonia of rat. For thioacetamide (TAA)-induced hepatopathy rats, we observe that the proposed sensor can ...detect liver that undergoes acute–moderate hepatopathy with a p-value less than 0.05. The proposed sensor is an organic diode with vertical nanojunctions produced by using low-cost colloidal lithography. Its simple structure and low production cost facilitates the development of point-of-care technology. We also anticipate that the study is a starting point for investigating sophisticated breath-ammonia-related disease models.
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IJS, KILJ, NUK, PNG, UL, UM
Introduction: Hypervolemia is a prevalent comorbidity of chronic kidney disease (CKD) patients. Thiazide diuretics (THZ) are the most common treatment for volume overload and hypertension (HTN). This ...study examines the association between THZ usage and clinical outcomes among CKD patients in a nationwide cohort.
Method: The total number of patients in the study was 24,312. After matching with one non-user randomly selected from the CKD population, we identified 8501 patients in the THZ and the comparison cohorts. Cox proportional hazards regression analysis was conducted to estimate the associations of THZ on the incidence of all-cause mortality, end-stage renal disease (ESRD), congestive heart failure (CHF), acute myocardial infarction (AMI), peripheral arterial occlusive disease (PAOD), and stroke.
Results: The all-cause mortality rate was significantly lower in THZ users than in non-users (hazard ratio HR = 0.65, 95% confidence interval CI = 0.60–0.71). The THZ usage was associated with a lower incidence of ESRD, AMI, PAOD, and stroke (P<0.05). In subgroup analysis, some significant clinical outcomes were related with CKD stages 3 and 4 (P<0.05); however, there were no clinical associations in CKD stage 5. In further THZ subtype analysis, there were clinical associations with fewer deaths, ESRD, AMI, and PAOD accompanying chlorthalidone treatment. Moreover, the indapamide prescription was linked to lower mortality, ESRD, AMI, and PAOD prevalence. However, there were significantly greater incidences of ESRD, CHF, and AMI in the metolazone users.
Conclusion: THZ usage is associated with lower mortality and incidence of ESRD, AMI, PAOD, and stroke s in patients with CKD stages 3 and 4.
Leptin (Lep) is mainly, although not exclusively, secreted by adipocytes. In addition to regulating lipid metabolism, it is also a proinflammatory factor and involved in the development of ...neuropathic pain after peripheral nerve injuries (PNI) (Lim et al., 2009; Maeda et al., 2009) 1,2. Leptin or its messenger ribonucleic acid expression has been found in various brain regions normally and in the dorsal horn after PNI (Lim et al., 2009; Ur et al., 2002; La Cava et al., 2004; White et al., 2004) 1,3–5. However, the expression pattern of Lep and Leptin receptor (LepR) after preganglionic cervical root avulsion (PCRA) is still unknown. We provide data in this article related to Chang et al. (2017) 6. Here, our data showed a profound Lep and LepR expression in the neurons of dorsal root ganglion (DRG) after PCRA. Moreover, the expression of Lep and LepR were also identified in significant portions of the neurons and microglia located in the dorsal horn. The roles of these increased expressions in the development of neuropathic pain after PCRA deserve further study.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To the Editor:
As noted in the article by Johnson et al. (May 9 issue),
1
chronic kidney disease of unknown cause has gained worldwide attention in recent years. It is diagnosed in patients who ...reside in warm climates and in whom no other obvious cause of chronic kidney disease can be discerned. Diabetes and hypertension are the known major causes of chronic kidney disease. In addition to these causes, meticulous investigations are necessary to rule out other causes such as glomerulonephritis; cystic diseases; infections due to human immunodeficiency virus, hepatitis B virus, or hepatitis C virus; and chronic tubulointerstitial diseases . . .
Background Calcineurin inhibitors (CNIs) exhibit remarkable efficacy in atopic dermatitis (AD). Tacrolimus, one type of CNI, is prevalently used to treat AD. AD is a chronic inflammatory disease that ...exhibits predominant infiltration of T-helper type 2 (Th2) cell in the acute phase and a mixed Th1 and Th0 cell pattern in chronic lesions. Cytokines such as tumor necrosis factor-α (TNF-α), Th2-related chemokines e.g., macrophage-derived chemokine (MDC)/CCL22 and I-309/CCL1, Th1-related chemokines e.g., interferon γ-induced protein 10 (IP-10)/CXCL10, and neutrophil chemoattractant growth-related oncogene-α (GRO-α)/CXCL1 are involved in the pathogenesis of AD. However, whether tacrolimus modulates the expression of AD-associated cytokines and chemokines remains unknown. The intracellular mechanisms of tacrolimus are also unclear. Methods Human monocytic cell line THP-1 cells were pretreated with tacrolimus and stimulated with lipopolysaccharide (LPS). The MDC, I-309, IP-10, GRO-α, and TNF-α concentrations of the cell supernatants were measured using enzyme-linked immunosorbent assay. Intracellular signaling was investigated using the Western blot analysis. Results Tacrolimus suppressed the expression of MDC, IP-10, I-309, GRO-α, and TNF-α in LPS-stimulated THP-1 cells in a dose- and time-dependent manner. All three mitogen-activated protein kinase (MAPK) inhibitors and the nuclear factor-κB inhibitor suppressed LPS-induced MDC, I-309, and TNF-α expressions in THP-1 cells. Only MAPK inhibitors suppressed LPS-induced expression of IP-10 and GRO-α. Tacrolimus suppressed the LPS-induced phosphorylation of MAPK-extracellular signal-related kinase (ERK). Conclusion Tacrolimus suppressed LPS-induced MDC, I-309, IP-10, GRO-α, and TNF-α expressions in monocytes through the MAPK-ERK pathway; thus, tacrolimus may yield therapeutic efficacy by modulating AD-associated cytokines and chemokines.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
People with hepatocellular carcinoma who undergo transcatheter arterial chemoembolization usually experience back pain due to lie supine for at least 4 hours to avoid bleeding and hematoma. Body ...positioning is an effective and safe method for decreasing back pain in people with transfemoral cardiac catheterization; however, its effects and safety among patients with high bleeding tendency are unknown.
To investigate whether body positioning could decrease back pain without increasing the chance of bleeding after transcatheter arterial chemoembolization.
A single-blind randomized controlled trial (ClinicalTrials.gov No.: NCT03784469).
A total of 78 people with liver cancer who had undergone chemoembolization through the femoral artery were enrolled. Each person was randomly assigned to either the control or intervention group (each consisted of 39 participants). The control group received the usual care, remaining flat and lying in a supine position, whereas the intervention group had their positions changed in the second and fourth hour after chemoembolization. Participants’ pain level was rated by using numerical rating scale -11 (score from 0 to 10), bleeding was measured by using volume of blood (cc.) in gauze and hematoma size in diameter (cm), and satisfaction was self-rated from 1 to 5. Repeated-measure analysis of variance (ANOVA) was used to compare the difference in pain levels over time within each group and independent t test to compare the mean difference of pain between groups at 5 endpoints, both methods with Bonferroni adjustment. Independent t test, chi-squared test, and Fisher's exact test compared postembolization discomfort, puncture sites bleeding, satisfaction between groups.
Significant changes of pain levels over time in both intervention F(2.93, 111.20)=7.64, p<.001 and control groups F(2.66, 101.17)=20.55, p<.001. The intervention group had a significantly lower mean pain score in the second hour (t = −2.838, p = .006) and fourth hour (t = −4.739, p < .001) when patients turning to the side than did the control group lying supine. Furthermore, patients in the intervention group had significantly higher satisfaction than did those in the control group (t = −2.422, p = .018). No hematoma and significant difference of post-procedural bleeding between groups.
Changing patients’ body positions in bed after transcatheter arterial chemoembolization is a safe and effective method of decreasing back pain, and increasing patients’ satisfaction, without increasing the complications of bleeding and hematoma. Clinicians should change the positions of people with hepatocellular carcinoma 2 hours after they receive transcatheter arterial chemoembolization.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Surgery is the first-line therapy for glioblastoma. There is evidence that extent of resection is significantly associated with patient survival. Unfortunately, optimal surgical resection is usually ...limited because of the difficulty in discriminating tumor-infiltrated region and normal brain tissue. This study aimed to develop a tool to distinguish between infiltration zone and normal tissue in real time during glioma surgery.
In an in vivo study, C6 glioma cells were implanted into the left cerebral hemispheres of 6 rats to mimic tumorigenesis. A newly designed optical fiber-embedded needle probe was used to measure the autofluorescence of both cerebral hemispheres at various depths 5 days after the implantation. These rats were then sacrificed, and both cerebral hemispheres were removed for histopathologic analysis.
Comparative analyses of corresponding areas by histopathology and autofluorescence revealed highly significant (P < 0.001) differences among the normal tissue, infiltration zone, tumors, and the contralateral cerebral hemispheres. The area of the receiver operating characteristic curve was 0.978, and the sensitivity and specificity of tumor delineation were 93.9% and 94.4%, respectively.
The newly designed in vivo fiber-optic probe can distinguish tumor-infiltration zones from normal brain tissue in this in vivo study. Therefore, it may help neurosurgeons to increase extent of resection without damaging normal brain tissue and thus potentially improve the patients' survival and quality of life.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Senescence reduces the circulating number and angiogenic activity of endothelial progenitor cells (EPCs), and is associated with aging-related vascular diseases. However, it is very time-consuming to ...obtain aged cells (~1 month of repeated replication) or animals (~2 years) for senescence studies. Here, we established an accelerated senescence model by treating EPCs with deferoxamine (DFO), an FDA-approved iron chelator. Four days of low-dose (3 μM) DFO induced senescent phenotypes in EPCs, including a senescent pattern of protein expression, impaired mitochondrial bioenergetics, altered mitochondrial protein levels and compromised angiogenic activity. DFO-treated early EPCs from young and old donors (< 35 vs. > 70 years old) displayed similar senescent phenotypes, including elevated senescence-associated β-galactosidase activity and reduced relative telomere lengths, colony-forming units and adenosine triphosphate levels. To validate this accelerated senescence model
, we intraperitoneally injected Sprague-Dawley rats with DFO for 4 weeks. Early EPCs from DFO-treated rats displayed profoundly senescent phenotypes compared to those from control rats. Additionally, in hind-limb ischemic mice, DFO pretreatment compromised EPC angiogenesis by reducing both blood perfusion and capillary density. DFO thus accelerates EPC senescence and appears to hasten model development for cellular senescence studies.
Preganglionic cervical root avulsion (PCRA) affects both the peripheral and central nervous systems and is often associated with neuropathic pain. Unlike peripheral nerve injuries (PNI), central ...lesions caused by disruption of cervical roots from the spinal cord following PCRA contribute to the generation of neuropathic pain. Leptin is involved in the development of neuropathic pain after PNI by affecting neurons. However, whether leptin is involved in microglial activation leading to neuropathic pain after PCRA is unknown.
Preganglionic avulsion of the left 6th–8th cervical roots was performed in C57B/6J mice and leptin-deficient mice. A leptin antagonist or leptin was administered to C57B/6J mice and leptin-deficient mice after injury, respectively. The expression pattern of spinal and supraspinal microglia was examined by immunofluorescent staining. Von Frey filaments were used to test pain sensitivity.
Leptin is essential for the development of neuropathic pain after PCRA. Allodynia was absent in the leptin-deficient mice and the mice administered the leptin antagonist. We also found that leptin deficiency or the administration of its antagonist inhibited the development of microgliosis in the dorsal horn and brainstem. Furthermore, increase in the expression of CD86 and iNOS, and Wallerian degeneration were noted in the spinal cord. The administration of exogenous leptin to leptin-deficient mice reversed these effects.
We concluded that leptin is involved in the proliferation and activation of microglia, which in turn enhances the development of neuropathic pain. Blocking the effects of leptin might be a target for the treatment of neuropathic pain after PCRA.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP