Measurement of the Positive Muon Anomalous Magnetic Moment to 0.20 ppm.

We present a new measurement of the positive muon magnetic anomaly, a_{µ}≡(g_{µ}-2)/2, from the Fermilab Muon g-2 Experiment using data collected in 2019 and 2020. We have analyzed more than 4 times the number of positrons from muon decay than in our previous result from 2018 data. The systematic error is reduced by more than a factor of 2 due to better running conditions, a more stable beam, and improved knowledge of the magnetic field weighted by the muon distribution, ω[over ˜]_{p}^{'}, and of the anomalous precession frequency corrected for beam dynamics effects, ω_{a}. From the ratio ω_{a}/ω[over ˜]_{p}^{'}, together with precisely determined external parameters, we determine a_{µ}=116 592 057(25)×10^{-11} (0.21 ppm). Combining this result with our previous result from the 2018 data, we obtain a_{µ}(FNAL)=116 592 055(24)×10^{-11} (0.20 ppm). The new experimental world average is a_{µ}(exp)=116 592 059(22)×10^{-11} (0.19 ppm), which represents a factor of 2 improvement in precision.

What has the National Cancer Database taught us about oral cavity squamous cell carcinoma?

The wealth of data in the National Cancer Database (NCDB) has allowed numerous studies investigating patient, disease, and treatment-related factors in oral cavity squamous cell carcinoma (OCSCC); however, to date, no summation of these studies has been performed. The aim of this study was to provide a concise review of the NCDB studies on OCSCC, with the hopes of providing a framework for future, novel studies aimed at enhancing our understanding of clinical parameters related to OCSCC. Two databases were searched, and 27 studies published between 2002 and 2020 were included. The average sample size was 13,776 patients (range 356-50,896 patients). Four areas of research focus were identified: demographic and socioeconomic status, diagnosis, prognosis, and treatment. This review highlights the impact of age, sex, ethnicity, and socioeconomic status on the prognosis and management of OCSCC, describes the prognostic factors, and details the modalities and indications for neck dissection and adjuvant therapy in OCSCC. In conclusion, the NCDB is a very valuable resource for clinicians and researchers involved in the management of OCSCC, offering an incomparable perspective on a large dataset of patients. Future developments regarding hospital information management, review of data accuracy and completeness, and wider accessibility will help clinicians to improve the care of patients affected by OCSCC.

Measurement of the Positive Muon Anomalous Magnetic Moment to 0.46 ppm.

We present the first results of the Fermilab National Accelerator Laboratory (FNAL) Muon g-2 Experiment for the positive muon magnetic anomaly a_{µ}≡(g_{µ}-2)/2. The anomaly is determined from the precision measurements of two angular frequencies. Intensity variation of high-energy positrons from muon decays directly encodes the difference frequency ω_{a} between the spin-precession and cyclotron frequencies for polarized muons in a magnetic storage ring. The storage ring magnetic field is measured using nuclear magnetic resonance probes calibrated in terms of the equivalent proton spin precession frequency ω[over ˜]_{p}^{'} in a spherical water sample at 34.7 °C. The ratio ω_{a}/ω[over ˜]_{p}^{'}, together with known fundamental constants, determines a_{µ}(FNAL)=116 592 040(54)×10^{-11} (0.46 ppm). The result is 3.3 standard deviations greater than the standard model prediction and is in excellent agreement with the previous Brookhaven National Laboratory (BNL) E821 measurement. After combination with previous measurements of both µ^{+} and µ^{-}, the new experimental average of a_{µ}(Exp)=116 592 061(41)×10^{-11} (0.35 ppm) increases the tension between experiment and theory to 4.2 standard deviations.

The fate of the bone graft in cerebrospinal fluid rhinorrhea endoscopic repair for idiopathic intracranial hypertension: a retrospective case series analysis.

INTRODUCTION: Idiopathic intracranial hypertension (IIH) is a common cause of spontaneous cerebrospinal fluid (CSF) leaks necessitating surgical intervention, and grafting of septal, mastoid, or turbinate bone over the defect is increasingly performed to strengthen the repair of the primary defect. However, the postoperative fate of these grafted bone fragments is largely unknown. METHODOLOGY: We performed a retrospective study of patients at the University of Pennsylvania undergoing repair of spontaneous CSF leaks secondary to IIH. Preoperative and postoperative CTs were analyzed to determine the integration status of the transplanted bone. RESULTS: Fourteen patients with IIH and spontaneous CSF leak were analyzed, with a mean postoperative imaging follow-up period of four years. Thirteen patients (93%) had bone present on CT imaging, with 11 of these patients displaying evidence of bone integration. Two patients (14%) had a recurrent CSF leak in the same area, including the patient with absence of bone on imaging follow-up. CONCLUSIONS: Bone grafts frequently incorporate when used for repair of spontaneous CSF leaks associated with IIH. The rate of incorporation is comparable to bone grafts used for other etiologies of CSF leak, despite the increased pressure on the repair site. Any rigid repair of the leak site should likely be accompanied by treatment of the underlying intracranial hypertension to avoid leak recurrence.

Dopaminergic Immunofluorescence Studies in Kidney Tissue.

The kidney is a highly integrated system of specialized differentiated cells that are responsible for fluid and electrolyte balance in the body. While much of today's research focuses on isolated nephron segments or cells from nephron segments grown in tissue culture, an often overlooked technique that can provide a unique view of many cell types in the kidney is slice culture. Here, we describe techniques that use freshly excised kidney tissue from rats to perform a variety of experiments shortly after isolating the tissue. By slicing the rat kidney in a "bread loaf" format, multiple studies can be performed on slices from the same tissue in parallel. Cryosectioning and staining of the tissue allow for the evaluation of physiological or biochemical responses in a wide variety of specific nephron segments. The procedures described within this chapter can also be extended to human or mouse kidney tissue.

Risk factors for adult acquired subglottic stenosis.

OBJECTIVE: The aetiology and outcomes for patients with acquired subglottic stenosis are highly variable. This study aimed to identify risk factors for subglottic stenosis and patient characteristics that predict long-term clinical outcomes. METHODS: A retrospective review was performed on 63 patients with subglottic stenosis and 63 age-matched controls. Patient demographics and clinical characteristics were compared. Subglottic stenosis patients were further grouped according to tracheostomy status (i.e. tracheostomy never required, tracheostomy initially required but patient eventually decannulated, and tracheostomy-dependent). Patient factors from these three groups were then compared to evaluate risk factors for long-term tracheostomy dependence. RESULTS: Compared to controls, patients with subglottic stenosis had a significantly higher body mass index (30.8 vs 26.0 kg/m2; p < 0.001) and were more likely to have diabetes (23.8 per cent vs 7.94 per cent; p = 0.01). Comparing tracheostomy outcomes within the subglottic stenosis group, body mass index trended towards significance (p = 0.08). Age, gender, socio-economic status, subglottic stenosis aetiology and other co-morbidities did not correlate with outcome. CONCLUSION: Obesity and diabetes are significant risk factors for acquiring subglottic stenosis. Further investigations are required to determine if obesity is also a predictor for failed tracheostomy decannulation in subglottic stenosis.

Anticholinergic medication use is associated with globus pharyngeus.

BACKGROUND: Globus pharyngeus has been linked to salivary hypofunction. We hypothesise that a considerable portion of the globus experienced by patients is due to a drying effect secondary to anticholinergic medication use; this study aimed to determine their association. METHODS: A cross-sectional study was conducted of 270 patients who presented to a laryngology practice over 6 months. Participants rated globus sensation on a 5-point severity scale, with those scoring 0 considered as controls (non-globus). Participants were excluded if they had a likely cause of globus. Scores were compared with participants' medication lists, co-morbidities, age and gender, and evaluated using multivariate analysis, with significance set at p < 0.05. RESULTS: Any participant taking at least 2 anticholinergic medications had a 3.52 increased odds (p = 0.02) of experiencing globus. A previous diagnosis of gastroesophageal reflux disease was also significantly associated with globus (p = 0.004), with an odds ratio of 3.75. CONCLUSION: A substantial portion of idiopathic globus may be due to anticholinergic use or reflux. The findings implicate medication use as a risk factor for globus. An awareness of these associations is invaluable for identifying cause and treating globus.

Measurement of muon capture on the proton to 1% precision and determination of the pseudoscalar coupling gP.

The MuCap experiment at the Paul Scherrer Institute has measured the rate Λ(S) of muon capture from the singlet state of the muonic hydrogen atom to a precision of 1%. A muon beam was stopped in a time projection chamber filled with 10-bar, ultrapure hydrogen gas. Cylindrical wire chambers and a segmented scintillator barrel detected electrons from muon decay. Λ(S) is determined from the difference between the µ(-) disappearance rate in hydrogen and the free muon decay rate. The result is based on the analysis of 1.2 × 10(10) µ(-) decays, from which we extract the capture rate Λ(S) = (714.9 ± 5.4(stat) ± 5.1(syst)) s(-1) and derive the proton's pseudoscalar coupling g(P)(q(0)(2) = -0.88 m(µ)(2)) = 8.06 ± 0.55.

Measurement of the positive muon lifetime and determination of the Fermi constant to part-per-million precision.

We report a measurement of the positive muon lifetime to a precision of 1.0 ppm; it is the most precise particle lifetime ever measured. The experiment used a time-structured, low-energy muon beam and a segmented plastic scintillator array to record more than 2×10(12) decays. Two different stopping target configurations were employed in independent data-taking periods. The combined results give τ(µ(+)) (MuLan)=2 196 980.3(2.2) ps, more than 15 times as precise as any previous experiment. The muon lifetime gives the most precise value for the Fermi constant: G(F) (MuLan)=1.166 378 8(7)×10(-5) GeV(-2) (0.6 ppm). It is also used to extract the µ(-)p singlet capture rate, which determines the proton's weak induced pseudoscalar coupling g(P).

Search for Lorentz and CPT violation effects in Muon spin precession.

The spin precession frequency of muons stored in the (g-2) storage ring has been analyzed for evidence of Lorentz and CPT violation. Two Lorentz and CPT violation signatures were searched for a nonzero delta omega a(=omega a mu+ - omega a mu-) and a sidereal variation of omega a mu+/-). No significant effect is found, and the following limits on the standard-model extension parameters are obtained: bZ = -(1.0+/-1.1) x 10(-23) GeV; (m mu dZ0 + HXY)=(1.8+/-6.0) x 10(-23) GeV; and the 95% confidence level limits b perpendicular mu+ <1.4 x 10(-24) GeV and b perpendicular mu- <2.6 x 10(-24) GeV.

Improved measurement of the positive-muon lifetime and determination of the Fermi constant.

The mean life of the positive muon has been measured to a precision of 11 ppm using a low-energy, pulsed muon beam stopped in a ferromagnetic target, which was surrounded by a scintillator detector array. The result, tau(micro)=2.197 013(24) micros, is in excellent agreement with the previous world average. The new world average tau(micro)=2.197 019(21) micros determines the Fermi constant G(F)=1.166 371(6)x10(-5) GeV-2 (5 ppm). Additionally, the precision measurement of the positive-muon lifetime is needed to determine the nucleon pseudoscalar coupling g(P).

Measurement of the negative muon anomalous magnetic moment to 0.7 ppm.

The anomalous magnetic moment of the negative muon has been measured to a precision of 0.7 ppm (ppm) at the Brookhaven Alternating Gradient Synchrotron. This result is based on data collected in 2001, and is over an order of magnitude more precise than the previous measurement for the negative muon. The result a(mu(-))=11 659 214(8)(3) x 10(-10) (0.7 ppm), where the first uncertainty is statistical and the second is systematic, is consistent with previous measurements of the anomaly for the positive and the negative muon. The average of the measurements of the muon anomaly is a(mu)(exp)=11 659 208(6) x 10(-10) (0.5 ppm).

Measurement of the positive muon anomalous magnetic moment to 0.7 ppm.

A higher precision measurement of the anomalous g value, a(mu)=(g-2)/2, for the positive muon has been made at the Brookhaven Alternating Gradient Synchrotron, based on data collected in the year 2000. The result a(mu(+))=11 659 204(7)(5)x10(-10) (0.7 ppm) is in good agreement with previous measurements and has an error about one-half that of the combined previous data. The present world average experimental value is a(mu)(expt)=11 659 203(8)x10(-10) (0.7 ppm).

Angiotensin type 2 receptor-mediated hypotension in angiotensin type-1 receptor-blocked rats.

The type-2 (AT(2)) angiotensin (Ang) II receptor has been characterized as potentially counterregulatory to the actions of Ang II at its type-1 (AT(1)) receptor. We investigated the effects of Ang II and CGP-42112A (CGP), a selective peptide AT(2) receptor agonist, on blood pressure (BP) in rats with or without pharmacological blockade of the AT(1) receptor with losartan (LOS) or valsartan (VAL). In anesthetized rats (n=5 per group) receiving normal sodium intake, Ang II (200 pmol/kg per minute IV) alone increased BP from a control of 112+/-3 to 168+/-7 mm Hg (P<0.001) and LOS (30 mg/kg) alone decreased BP to 89+/-7 mm Hg (P<0.0001 from control). Ang II administered together with LOS decreased BP further to 71+/-4 mm Hg (P<0.00001 from control and LOS alone). AT(2) receptor antagonist PD 123,319 (PD) completely blocked the hypotensive response to LOS combined with Ang II (P=NS from control). In conscious rats (n=5 per group) receiving normal sodium intake, VAL (10 mg/kg) alone decreased BP from a control of 98+/-5 to 86+/-3 mm Hg (P<0.00001). Ang II combined with VAL induced a consistent, highly significant decline in BP for 6 days to a nadir of 69+/-3 mm Hg (P<0.01 versus daily VAL alone). PD completely blocked the chronic hypotensive response to the combination of Ang II and VAL to control levels before VAL administration. In another study in conscious rats (n=5 per group), CGP (70 microg/kg per minute) also decreased BP in VAL-treated conscious rats. BP was 119+/-3 mm Hg during the control period, decreased to 86+/-6 mm Hg during 3 days of VAL alone, (P<0.00001) and decreased further to 65+/-7 mm Hg (P<0.001 from daily VAL alone) with 7 days of CGP in the presence of VAL. In the absence of VAL, CGP decreased BP for 4 consecutive days, and this response was blocked by PD. Also, the CGP-induced decrease in BP over a 7-day period was blocked by N(G)-nitro-L-arginine methyl ester, an inhibitor of NO synthase. The results strongly suggest that the AT(2) receptor induces a systemic vasodilator response mediated by NO that counterbalances the vasoconstrictor action of Ang II at the AT(1) receptor.

Theodore Cooper Lecture: Renal dopamine system: paracrine regulator of sodium homeostasis and blood pressure.

All of the components of a complete dopamine system are present within the kidney, where dopamine acts as a paracrine substance in the control of sodium excretion. Dopamine receptors can be divided into D(1)-like (D(1) and D(5)) receptors that stimulate adenylyl cyclase and D(2)-like (D(2), D(3), and D(4)) receptors that inhibit adenylyl cyclase. All 5 receptor subtypes are expressed in the kidney, albeit in low copy. Dopamine is synthesized extraneuronally in proximal tubule cells, exported from these cells largely into the tubule lumen, and interacts with D(1)-like receptors to inhibit the Na(+)-H(+) exchanger and Na(+),K(+)-ATPase, decreasing tubule sodium reabsorption. During moderate sodium surfeit, dopamine tone at D(1)-like receptors accounts for approximately 50% of sodium excretion. In experimental and human hypertension, 2 renal dopaminergic defects have been described: (1) decreased renal generation of dopamine and (2) a D(1) receptor-G protein coupling defect. Both defects lead to renal sodium retention, and each may play an important role in the pathophysiology of essential hypertension.

Renal interstitial cGMP mediates natriuresis by direct tubule mechanism.

The objective of this study was to test the hypothesis that renal interstitial (RI) cGMP is natriuretic in vivo. In conscious rats (n=8), urinary sodium excretion (U(Na)V) was significantly greater on days 3 and 4 of RI infusion of cGMP (1.17+/-0.14 and 1.61+/-0.11 mmol/24 h, respectively) than during vehicle infusion (0.56+/-0.15 and 0.70+/-0.17 mmol/24 h, respectively) (P<0.01). Similarly, U(Na)V was greater on days 3 and 4 of RI infusion of 8-bromo-cGMP (2.15+/-0.42 and 2.16+/-0.1 mmol/24 h, respectively). Protein kinase G inhibitor Rp-8-pCPT-cGMPS reduced cGMP-induced and 8-bromo-cGMP-induced U(Na)V to control levels. Acute RI infusion of L-arginine (L-Arg, 40 mg. kg(-1). min(-1)), but not D-arginine, caused an increase in U(Na)V from 1.65+/-0.11 to 4.07+/-0.1 micromol/30 min (P<0.01). This increase was blocked by RI infusion of N(G)-nitro-L-arginine methyl ester (100 ng. kg(-1). min(-1)) by the phosphodiesterase (PDE II) activator 5,6DMcBIMP (0.01 micromol/microL), by PDE II (0.03 U. kg(-1). min(-1)) itself, or by the soluble guanylyl cyclase inhibitor 1-H-[1,2,4]oxadiazolo-[4,2-alpha]quinoxalin-1-one (ODQ, 0.12 mg. kg(-1). min(-1)). The PDE II activator also blocked L-Arg-stimulated cGMP levels. The NO donor S-nitroso-N-acetylpenicillamine (SNAP, 0.12 micromol. L(-1). kg(-1). min(-1)) increased U(Na)V from 1.65+/-0.11 to 2.93+/-0.08 micromol/30 min (P<0.01), and this response was blocked completely by ODQ. Renal arterial but not RI administration of the heat-stable enterotoxin of Escherichia coli induced natriuresis. RA infusion of cGMP (3 microg/min) increased U(Na)V, renal blood flow (RBF), and glomerular filtration rate (GFR). Renal cortical interstitial cGMP infusion increased U(Na)V with no effect on total RBF, renal cortical blood flow, or GFR. Similarly, the natriuretic actions of renal interstitial L-Arg or SNAP were not accompanied by any change in RBF or GFR. Medullary cGMP infusion had no effect on U(Na)V, total RBF, or medullary blood flow. Texas red-labeled cGMP infused via the RI space was distributed exclusively to cortical renal tubular cells. The results demonstrate that RI cGMP inhibits renal tubular sodium absorption via protein kinase G independently of hemodynamic changes. These observations indicate that the cortical interstitial compartment provides a potentially important domain for cell-to-cell signaling within the kidney.

Angiotensin-converting enzyme inhibition potentiates angiotensin II type 1 receptor effects on renal bradykinin and cGMP.

Angiotensin (Ang) receptor blockers (ARBs) increase bradykinin (BK) by antagonizing Ang II at its type 1 (AT(1)) receptors and diverting Ang II to its counterregulatory type 2 (AT(2)) receptors. Because the effect of ARBs on BK is constrained by the short half-life of BK and because ACE inhibitors block the degradation of BK, this study was designed to test the hypothesis that an ACE inhibitor can potentiate ARB-induced increases in renal interstitial fluid (RIF) BK levels. We used a microdialysis technique to recover BK and cGMP in vivo from the RIF of sodium-depleted, conscious Sprague-Dawley rats infused for 60 minutes with the AT(1) receptor blocker valsartan (0.17 mg/kg per minute), with the active metabolite of the ACE inhibitor benazepril (benazeprilate, 0.05 mg/kg per minute), or with the specific AT(2) receptor blocker PD 123,319 (50 microg/kg per minute) alone or combined. Each animal served as its own control. RIF BK and cGMP levels increased significantly over 1 hour in response to valsartan, benazeprilate, or both but not to a vehicle control (P<0.01). The combined benazeprilate-valsartan effect was greater than the sum of their individual effects, suggesting potentiation rather than addition, and was abolished by PD 123,319. We demonstrate for the first time that an ACE inhibitor (benazepril) and an ARB (valsartan) potentiate each other, and we postulate that such combinations may be beneficial in clinical states marked by Ang II elevation, such as chronic heart failure, postinfarction left ventricular dysfunction, and hypertension.

Distribution of type-1 and type-2 angiotensin receptors in the normal human lung and in lungs from patients with chronic obstructive pulmonary disease.

This study was designed to examine the cellular distribution of the angiotensin II type-1 (AT1) and type-2 (AT2) receptors in the normal human and pathological human lung. Riboprobes were prepared against specific portions of each receptor DNA and labelled with FITC for detection using an anti-FITC antibody in combination with the alkaline phosphatase-anti-alkaline phosphatase technique and new Fuchsin. These were used to detect the presence of receptor mRNA in the lung. Specific antibodies were used to detect receptor protein in cells by immunocytochemistry. Image analysis was used in order to semi-quantify receptor density. AT1 receptor mRNA and protein were localised on vascular smooth muscle cells, macrophages and in the stroma underlying the airways epithelium probably relating to underlying fibroblasts. The AT1 receptor protein was not expressed in the epithelium although there was a low level of mRNA. In contrast, AT2 receptor RNA and protein was observed in the epithelium, with strong staining on the bronchial epithelial cell brush border and also on many of the underlying mucous glands. The AT2 receptor was also present on some endothelial cells. These findings were supported by the presence of mRNA in each case. In patients with chronic obstructive pulmonary disease, there was a five- to sixfold increase in the ratio of AT1 to AT2 receptors in the regions of marked fibrosis surrounding the bronchioles. This correlated well with the reduced lung function as expressed by the forced expiratory volume.

Vascular expression of angiotensin type 2 receptor in the adult rat: influence of angiotensin II infusion.

OBJECTIVE: The aim of this study was to investigate the relative role of the angiotensin type 1 (AT1) and type 2 (AT2) receptors in mediating angiotensin II-induced regulation of AT2 receptor in mesenteric artery. DESIGN: Sprague-Dawley rats were infused with either angiotensin II or vehicle for 14 days at a dose of 58.3 ng/min. Ang II-infused rats were allocated to receive either an AT1 antagonist, valsartan at a dose of 30 mg/kg per day or the AT2 receptor antagonist PD123319 at a dose of 830 ng/min. METHODS: Gene and protein expression of the AT2 receptor in the mesenteric vasculature was assessed by quantitative reverse transcriptase polymerase chain reaction, immunohistochemistry and by in vitro autoradiography with a specific radioligand, 1251-CGP 42112B. RESULTS: The AT2 receptor mRNA and protein were detected in the mesenteric artery from adult rats. Both nuclear emulsion and immunohistochemical staining showed expression of the AT2 receptor in the adventitial and medial layers. Compared to control rats, angiotensin II infusion was associated with a significant increase in the AT2 receptor expression. Valsartan treatment significantly reduced AT2 receptor gene expression, with no significant effect of PD123319 on this parameter. CONCLUSIONS: This study confirms that the presence of the AT2 receptor in mesenteric arteries in adult rats, shows an up-regulation of the AT2 receptor following angiotensin II infusion and suggests a role for the AT1 receptor in this regulation. In view of the recently demonstrated effects of the AT2 receptor, these findings may be relevant to the role of the AT2 receptor in the pathophysiology of vascular remodeling.

Role of the angiotensin AT2 receptor in blood pressure regulation and therapeutic implications.

The angiotensin (ANG) Type 2 (AT2) receptor is one of two major ANG II receptors that have been identified, cloned, and sequenced. Most of the biologic actions of ANG II are thought to be mediated by the AT1 receptor, but evidence is beginning to emerge that the AT2 receptor has a significant role in the regulation of blood pressure. In the adult rat, the AT2 receptor is expressed, albeit in low concentrations in kidney, mesenteric blood vessels, and heart. Most of the evidence suggests that the AT2 receptor stimulates a vasodilator signaling cascade that includes bradykinin, nitric oxide, and guanosine cyclic 3',5'-monophosphate. At lease some of the beneficial actions of AT1 receptor blockade are mediated by the AT2 receptor through this pathway. Several recent studies suggest that AT2 receptors may mediate vasodilation and hypotension. The AT2 receptor represents a potential therapeutic target for agonist action and a candidate molecule in the pathophysiology of hypertension.