Experiences that matter in bipolar disorder: a qualitative study using the capability, comfort and calm framework.

BACKGROUND: When assessing the value of an intervention in bipolar disorder, researchers and clinicians often focus on metrics that quantify improvements to core diagnostic symptoms (e.g., mania). Providers often overlook or misunderstand the impact of treatment on life quality and function. We wanted to better characterize the shared experiences and obstacles of bipolar disorder within the United States from the patient's perspective. METHODS: We recruited 24 individuals diagnosed with bipolar disorder and six caretakers supporting someone with the condition. Participants were involved in treatment or support services for bipolar disorder in central Texas. As part of this qualitative study, participants discussed their everyday successes and obstacles related to living with bipolar disorder during personalized, open-ended interviews. Audio files were transcribed, and Nvivo software processed an initial thematic analysis. We then categorized themes into bipolar disorder-related obstacles that limit the patient's capability (i.e., function), comfort (i.e., relief from suffering) and calm (i.e., life disruption) (Liu et al., FebClin Orthop 475:315-317, 2017; Teisberg et al., MayAcad Med 95:682-685, 2020). We then discuss themes and suggest practical strategies that might improve the value of care for patients and their families. RESULTS: Issues regarding capability included the struggle to maintain identity, disruptions to meaningful employment, relationship loss and the unpredictable nature of bipolar disorder. Comfort related themes included the personal perception of diagnosis, social stigma and medication issues. Calm themes included managing dismissive doctors, finding the right psychotherapist and navigating financial burdens. CONCLUSIONS: Qualitative data from patients with bipolar disorder helps identify gaps in care or practical limitations to treatment. When we listen to these individuals, it is clear that treatments must also address the unmet psychosocial impacts of the condition to improve patient care, capability and calm.

Reconstruction of Bloch wavefunctions of holes in a semiconductor.

A central goal of condensed-matter physics is to understand how the diverse electronic and optical properties of crystalline materials emerge from the wavelike motion of electrons through periodically arranged atoms. However, more than 90 years after Bloch derived the functional forms of electronic waves in crystals1 (now known as Bloch wavefunctions), rapid scattering processes have so far prevented their direct experimental reconstruction. In high-order sideband generation2-9, electrons and holes generated in semiconductors by a near-infrared laser are accelerated to a high kinetic energy by a strong terahertz field, and recollide to emit near-infrared sidebands before they are scattered. Here we reconstruct the Bloch wavefunctions of two types of hole in gallium arsenide at wavelengths much longer than the spacing between atoms by experimentally measuring sideband polarizations and introducing an elegant theory that ties those polarizations to quantum interference between different recollision pathways. These Bloch wavefunctions are compactly visualized on the surface of a sphere. High-order sideband generation can, in principle, be observed from any direct-gap semiconductor or insulator. We thus expect that the method introduced here can be used to reconstruct low-energy Bloch wavefunctions in many of these materials, enabling important insights into the origin and engineering of the electronic and optical properties of condensed matter.

Repurposing Disulfiram (Tetraethylthiuram Disulfide) as a Potential Drug Candidate against Borrelia burgdorferi In Vitro and In Vivo.

Lyme disease caused by the Borrelia burgdorferi (Bb or B. burgdorferi) is the most common vector-borne, multi-systemic disease in the USA. Although most Lyme disease patients can be cured with a course of the first line of antibiotic treatment, some patients are intolerant to currently available antibiotics, necessitating the development of more effective therapeutics. We previously found several drugs, including disulfiram, that exhibited effective activity against B. burgdorferi. In the current study, we evaluated the potential of repurposing the FDA-approved drug, disulfiram for its borreliacidal activity. Our results indicate disulfiram has excellent borreliacidal activity against both the log and stationary phase B. burgdorferi sensu stricto B31 MI. Treatment of mice with disulfiram eliminated the B. burgdorferi sensu stricto B31 MI completely from the hearts and urinary bladder by day 28 post infection. Moreover, disulfiram-treated mice showed reduced expressions of inflammatory markers, and thus they were protected from histopathology and cardiac organ damage. Furthermore, disulfiram-treated mice showed significantly lower amounts of total antibody titers (IgM and IgG) at day 21 and total IgG2b at day 28 post infection. FACS analysis of lymph nodes revealed a decrease in the percentage of CD19+ B cells and an increase in total percentage of CD3+ T cells, CD3+ CD4+ T helpers, and naive and effector memory cells in disulfiram-treated mice. Together, our findings suggest that disulfiram has the potential to be repurposed as an effective antibiotic for treating Lyme disease.

Myelin and Axonal Damage in Normal-Appearing White Matter in Patients with Moyamoya Disease.

BACKGROUND AND PURPOSE: Although chronic ischemia is known to induce myelin and axonal damage in animal models, knowledge regarding patients with Moyamoya disease is limited. We aimed to investigate the presence of myelin and axonal damage in Moyamoya disease and their relationship with cognitive performance. MATERIALS AND METHODS: Eighteen patients with Moyamoya disease (16-55 years of age) and 18 age- and sex-matched healthy controls were evaluated with myelin-sensitive MR imaging based on magnetization transfer saturation imaging and 2-shell diffusion MR imaging. The myelin volume fraction, which reflects the amount of myelin sheath; the g-ratio, which represents the ratio of the inner (axon) to the outer (axon plus myelin) diameter of the fiber; and the axon volume fraction, which reflects axonal components, were calculated and compared between the patients and controls. In the patients with Moyamoya disease, the relationship between these parameters and cognitive task-measuring performance speed was also evaluated. RESULTS: Compared with the healthy controls, the patients with Moyamoya disease showed a significant decrease in the myelin and axon volume fractions (P < .05) in many WM regions, while the increases in the g-ratio values were not statistically significant. Correlations with cognitive performance were most frequently observed with the axon volume fraction (r = 0.52-0.54; P < .03 in the right middle and posterior cerebral artery areas) and were the strongest with the g-ratio values in the right posterior cerebral artery region (r = 0.64; P = .004). CONCLUSIONS: Myelin-sensitive MR imaging and diffusion MR imaging revealed that myelin and axonal damage exist in patients with Moyamoya disease. The relationship with cognitive performance might be stronger with axonal damage than with myelin damage.

The utility of patent ductus arteriosus closure with hemostatic clip in dogs.

This study investigated the utility of patent ductus arteriosus (PDA) closure with hemostatic clip by comparing with traditional PDA closure. Medical records of 51 dogs with surgical closure of PDA were reviewed and retrospective study was conducted. 29 dogs were treated by procedure with hemostatic clip (Group HC), and 22 dogs were treated by surgical ligation (Group SL). Data pertaining to breed, sex, age and body weight at the time of surgery, echocardiographic minimal ductal diameter, duration of surgery, hemostatic clip size, echocardiographic findings, hemor-rhage, residual ductal flow and recanalization were collected from records. The results showed that procedure with hemostatic clip had been selected in lighter dogs than traditional PDA closure. Duration of surgery performed only hemostatic clip technique was significantly shorter than that in group SL. Preoperative LVIDd, E-wave and FS were significantly lower than postoperative ones. As regard all parameters, the differences between pre- and postoperative periods were not significantly different between group HC and group SL. Hemorrhage, residual ductal flow, and recanalization were not significantly different in both groups. The present study showed that procedure with hemostatic clip is beneficial in that it is available in smaller dogs and can make shorter operation duration than traditional PDA closure. Moreover, the procedure is effective for the resolution of volume overload of the left atrium and ventricle in short-term outcome. Complications including hemorrhage, residual ductal flow and recanaliza-tion were not significantly different with both techniques.

Azlocillin can be the potential drug candidate against drug-tolerant Borrelia burgdorferi sensu stricto JLB31.

Lyme disease is one of most common vector-borne diseases, reporting more than 300,000 cases annually in the United States. Treating Lyme disease during its initial stages with traditional tetracycline antibiotics is effective. However, 10-20% of patients treated with antibiotic therapy still shows prolonged symptoms of fatigue, musculoskeletal pain, and perceived cognitive impairment. When these symptoms persists for more than 6 months to years after completing conventional antibiotics treatment are called post-treatment Lyme disease syndrome (PTLDS). Though the exact reason for the prolongation of post treatment symptoms are not known, the growing evidence from recent studies suggests it might be due to the existence of drug-tolerant persisters. In order to identify effective drug molecules that kill drug-tolerant borrelia we have tested two antibiotics, azlocillin and cefotaxime that were identified by us earlier. The in vitro efficacy studies of azlocillin and cefotaxime on drug-tolerant persisters were done by semisolid plating method. The results obtained were compared with one of the currently prescribed antibiotic doxycycline. We found that azlocillin completely kills late log phase and 7-10 days old stationary phase B. burgdorferi. Our results also demonstrate that azlocillin and cefotaxime can effectively kill in vitro doxycycline-tolerant B. burgdorferi. Moreover, the combination drug treatment of azlocillin and cefotaxime effectively killed doxycycline-tolerant B. burgdorferi. Furthermore, when tested in vivo, azlocillin has shown good efficacy against B. burgdorferi in mice model. These seminal findings strongly suggests that azlocillin can be effective in treating B. burgdorferi sensu stricto JLB31 infection and furthermore in depth research is necessary to evaluate its potential use for Lyme disease therapy.

Wire-loop lesion is associated with serological immune abnormality, but not renal prognosis, in lupus nephritis.

BACKGROUND: Wire-loop lesion (WL) is one of the active lesions of lupus nephritis (LN). However, few reports have focused on the clinicopathological relationships of WL to serological immune abnormality and renal prognosis. METHODS: We enrolled 126 Japanese LN patients subjected to renal biopsy in 11 hospitals from 2000 to 2018. In patients with class III or IV of the International Society of Nephrology/Renal Pathology Society classification, we retrospectively compared clinicopathological findings between those with WL (WL+ group) and without WL (WL- group) to detect factors associated with WL. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate of <60 mL/min/1.73m2 for more than three months. We also compared these findings between those with CKD (CKD+ group) and without CKD (CKD- group) at the last visit to investigate factors associated with renal prognosis. RESULTS: Of 126 patients, 100 (79.4%) were classified as class III or IV. WL was found in 36 (36.0%) of them. Although the renal function did not differ, the WL+ group had a higher titre of serum anti-dsDNA antibodies and lower serum complement 3 levels than the WL- group. Linear regression analysis revealed a significant association only between anti-dsDNA antibodies and WL (ß = 0.27, 95% confidence interval (CI) 0.001-0.100, p = 0.01). Of these patients, 69 were tracked for 59.6 ± 55.1 months. Kaplan-Meier analysis showed no difference in renal prognosis between these groups. Next, the CKD+ group included 15 (22.1%) patients. They were older and had higher frequencies of hypertension and hyperuricaemia, serum creatinine (Cr) level, glomerulosclerosis, interstitial inflammation, interstitial fibrosis and tubular atrophy than the CKD- group at the time of renal biopsy. The frequency of WL was not significantly different. Cox regression analysis revealed significant associations of CKD with hypertension, hyperuricaemia, serum Cr level at the time of renal biopsy clinically and with tubular atrophy histologically. CONCLUSIONS: WL was associated with serum anti-dsDNA antibodies but not with renal prognosis, suggesting that WL reflects immune abnormality but is not an independent factor predictive of renal prognosis in LN.

Bayesian Estimation of CBF Measured by DSC-MRI in Patients with Moyamoya Disease: Comparison with 15O-Gas PET and Singular Value Decomposition.

BACKGROUND AND PURPOSE: CBF analysis of DSC perfusion using the singular value decomposition algorithm is not accurate in patients with Moyamoya disease. This study compared the Bayesian estimation of CBF against the criterion standard PET and singular value decomposition methods in patients with Moyamoya disease. MATERIALS AND METHODS: Nineteen patients with Moyamoya disease (10 women; 22-52 years of age) were evaluated with both DSC and 15O-gas PET within 60 days. DSC-CBF maps were created using Bayesian analysis and 3 singular value decomposition analyses (standard singular value decomposition, a block-circulant deconvolution method with a fixed noise cutoff, and a block-circulant deconvolution method that adopts an occillating noise cutoff for each voxel according to the strength of noise). Qualitative and quantitative analyses of the Bayesian-CBF and singular value decomposition-CBF methods were performed against 15O-gas PET and compared with each other. RESULTS: In qualitative assessments of DSC-CBF maps, Bayesian-CBF maps showed better visualization of decreased CBF on PET (sensitivity = 62.5%, specificity = 100%, positive predictive value = 100%, negative predictive value = 78.6%) than a block-circulant deconvolution method with a fixed noise cutoff and a block-circulant deconvolution method that adopts an oscillating noise cutoff for each voxel according to the strength of noise (P < .03 for all except for specificity). Quantitative analysis of CBF showed that the correlation between Bayesian-CBF and PET-CBF values (ρ = 0.46, P < .001) was similar among the 3 singular value decomposition methods, and Bayesian analysis overestimated true CBF (mean difference, 47.28 mL/min/100 g). However, the correlation between CBF values normalized to the cerebellum was better in Bayesian analysis (ρ = 0.56, P < .001) than in the 3 singular value decomposition methods (P < .02). CONCLUSIONS: Compared with previously reported singular value decomposition algorithms, Bayesian analysis of DSC perfusion enabled better qualitative and quantitative assessments of CBF in patients with Moyamoya disease.

Experimental study of fast-neutron production and moderation for accelerator-based BNCT system.

This work aims to study the fast-neutron production and moderation for the development of a compact accelerator-based multi-port Boron Neutron Capture Therapy (AB-mBNCT) system. An initial energy distribution and the efficiency of a test moderator assembly (TMA) for fast neutrons from a tungsten (W) target bombarded with a 53 MeV proton beam were measured using organic scintillators. The experimental results were reproduced with reasonable accuracy by simulations using the PHITS code. This paper will discuss about the experimental outcome and the related benchmark calculations by PHITS code.

Microwave oscillator using piezoelectric thin-film resonator aiming for ultraminiaturization of atomic clock.

We developed a microwave oscillator and a micro electromechanical systems-based rubidium cell for the miniaturization of atomic clocks. A thin-film bulk acoustic resonator (FBAR) having a resonant frequency of the fundamental mode in the 3.5 GHz band was employed instead of a crystal resonator. It delivers a clock transition frequency of Rb atoms of 3.417 GHz without the need for a complicated frequency multiplication using a phase-locked loop. This topology considerably reduces the system scale and power consumption. For downsizing the atomic clock system toward the chip level as well as mass production, a microfabricated gas cell containing Rb and N2 gases was also developed. These microcomponents were incorporated into an atomic clock test bench, resulting in a clock operation with a short-term frequency instability of 2.1 × 10-11 at 1 s. To the best of our knowledge, this is the first report of a coherent population trapping clock operation using an FBAR-based microwave oscillator as well as a microfabricated gas cell.

Thresholds of biodiversity and ecosystem function in a forest ecosystem undergoing dieback.

Ecological thresholds, which represent points of rapid change in ecological properties, are of major scientific and societal concern. However, very little research has focused on empirically testing the occurrence of thresholds in temperate terrestrial ecosystems. To address this knowledge gap, we tested whether a number of biodiversity, ecosystem functions and ecosystem condition metrics exhibited thresholds in response to a gradient of forest dieback, measured as changes in basal area of living trees relative to areas that lacked recent dieback. The gradient of dieback was sampled using 12 replicate study areas in a temperate forest ecosystem. Our results provide novel evidence of several thresholds in biodiversity (namely species richness of ectomycorrhizal fungi, epiphytic lichen and ground flora); for ecological condition (e.g. sward height, palatable seedling abundance) and a single threshold for ecosystem function (i.e. soil respiration rate). Mechanisms for these thresholds are explored. As climate-induced forest dieback is increasing worldwide, both in scale and speed, these results imply that threshold responses may become increasingly widespread.

Noninvasive Evaluation of CBF and Perfusion Delay of Moyamoya Disease Using Arterial Spin-Labeling MRI with Multiple Postlabeling Delays: Comparison with 15O-Gas PET and DSC-MRI.

BACKGROUND AND PURPOSE: Arterial spin-labeling MR imaging with multiple postlabeling delays has a potential to evaluate various hemodynamic parameters. To clarify whether arterial spin-labeling MR imaging can identify CBF and perfusion delay in patients with Moyamoya disease, we compared arterial spin-labeling, DSC, and 15O-gas PET in terms of their ability to identify these parameters. MATERIALS AND METHODS: Eighteen patients with Moyamoya disease (5 men, 13 women; ages, 21-55 years) were retrospectively analyzed. CBF values of pulsed continuous arterial spin-labeling using 2 postlabeling delays (short arterial spin-labeling, 1525 ms; delayed arterial spin-labeling, 2525 ms) were compared with CBF values measured by 15O-gas PET. All plots were divided into 2 groups by the cutoff of time-based parameters (the time of the maximum observed concentration, TTP, MTT, delay of MTT to cerebellum, and disease severity [symptomatic or not]). The ratio of 2 arterial spin-labeling CBFs (delayed arterial spin-labeling CBF to short arterial spin-labeling CBF) was compared with time-based parameters: time of the maximum observed concentration, TTP, and MTT. RESULTS: The short arterial spin-labeling-CBF values were significantly correlated with the PET-CBF values (r = 0.63; P = .01). However, the short arterial spin-labeling-CBF value dropped in the regions with severe perfusion delay. The delayed arterial spin-labeling CBF overestimated PET-CBF regardless of the degree of perfusion delay. Delayed arterial spin-labeling CBF/short arterial spin-labeling CBF was well correlated with the time of the maximum observed concentration, TTP, and MTT (ρ = 0.71, 0.64, and 0.47, respectively). CONCLUSIONS: Arterial spin-labeling using 2 postlabeling delays may detect PET-measured true CBF and perfusion delay in patients with Moyamoya disease. Provided its theoretic basis and limitations are considered, noninvasive arterial spin-labeling could be a useful alternative for evaluating the hemodynamics of Moyamoya disease.

The effect of aprepitant and dexamethasone combination on paclitaxel-induced hypersensitivity reaction.

PURPOSE OF INVESTIGATION: Dexamethasone (DEX) is often administered to prevent paclitaxel (PTX)-induced hypersensitivity reactions (HSR). The DEX dose is reduced when administered in combination with aprepitant (APR). However, the influence of that dose reduction on PTX-induced HSR has not been thoroughly studied. The present authors aimed to investigate the effects of the combined administration of APR and DEX on PTX-induced HSR. MATERIALS AND METHODS: Fifty-one patients who received a three-week PTX regimen in combination with APR and DEX were retrospectively analysed. The authors compared the dose of DEX with the incidence of HSR and other toxicities. RESULTS: Patients were stratified into two groups depending on the DEX dose, > 20 mg (group D, 33 patients), and < 12 mg (group reD, 26 patients). The incidence of HSR in Groups D and reD were 51.5% (17/33) and 53.8% (14/26), respectively. The frequencies of other toxicities between the groups were comparable. CONCLUSION: The findings suggest that although a reduction in DEX dose is possible when APR is co-administered, this does not affect the PTX-induced HSR. However, adverse effect should be closely monitored.

Intersex in the clam Scrobicularia plana (Da Costa): Widespread occurrence in English Channel estuaries and surrounding areas.

Estuarine clams Scrobicularia plana were sampled from 108 intertidal locations around the English Channel and adjacent areas. Although S. plana is believed to be a strict gonochorist, 58% of the populations sampled included intersexed individuals (described as male clams exhibiting ovotestis). Over the entire region, on average, 8.6% of male clams exhibited intersex, although proportions of affected males ranged from 0% to 53% depending on location. The severity of intersex was assessed using a simple classification scale, with the majority of individuals showing low levels of impact. Sex ratios were significantly skewed at some sites. There were no significant relationships between incidence or severity of intersex; or with size or parasitism of individual clams. Intersex in S. plana is a useful tool to assess endocrine disruptive effects in estuaries, although mechanisms of impact and causative agents remain uncertain.

Recovery from TBT pollution in English Channel environments: A problem solved?

Following recognition of effects in the 1980s, tributyltin (TBT) has been monitored at sites in the English Channel to evaluate the prognosis for biota - spanning the introduction of restrictions on TBT use on small boats and the recent phase-out on the global fleet. We describe how persistence and impact of TBT in clams Scrobicularia plana has changed during this period in Southampton Water and Poole Harbour. TBT contamination (and loss) in water, sediment and clams reflects the abundance and type of vessel activity: half-times in sediment (up to 8y in Poole, 33y in Southampton) are longest near commercial shipping. Recovery of clam populations - slowest in TBT-contaminated deposits - provides a useful biological measure of legislative efficacy in estuaries. On rocky shores, recovery from imposex in Nucella lapillus is evident at many sites but, near ports, is prolonged by shipping impacts, including sediment legacy, for example, in the Fal.

Fasting glucose and HbA1c levels as risk factors for the development of hypertension in Japanese individuals: Toranomon hospital health management center study 16 (TOPICS 16).

We investigated the effect of elevated concentrations of fasting plasma glucose (FPG) or hemoglobin A1c (HbA1c) on the risk of development of hypertension among apparently healthy Japanese. Studied were 9584 individuals without known diabetes and hypertension. During a 5-year follow-up period, 1098 individuals developed hypertension. Elevated concentrations of FPG, rather than of HbA1c, were significantly predictive of future hypertension. Compared with the lowest quartile category of FPG (<4.9 mmol l(-1)), the second (4.9-<5.2 mmol l(-1)), third (5.2-<5.6 mmol l(-1)) and highest (⩾ 5.6 mmol l(-1)) quartile categories had age-, sex- and body mass index-adjusted odds ratios (95% confidence interval) of 1.35 (1.10, 1.66), 1.39 (1.13, 1.71) and 1.85 (1.51, 2.28) for hypertension, respectively. In the highest quartile of FPG, the multivariate-adjusted OR was 1.37 (1.10, 1.70) compared with the lowest quartile. Results of these adjusted models showed no significant association across quartile categories of HbA1c concentrations and an increased risk of developing hypertension. The joint effect of hyperglycemia and overweight, older age or prehypertension resulted in further elevated ORs for hypertension than the absence of such an association. Higher FPG levels rather than HbA1c were strongly predictive of future hypertension among Japanese. Hyperglycemia along with older age, overweight and prehypertension contributed to identifying individuals at increased risk of developing hypertension.

Impact of tubulointerstitial lesions on anaemia in patients with biopsy-proven diabetic nephropathy.

AIMS: To investigate the relationship between the progression of anaemia and renal pathological findings in patients with diabetic nephropathy. METHODS: A total of 223 patients with diabetes underwent renal biopsy from 1985 to 2010 and were confirmed to have pure diabetic nephropathy according to the recent classification, of whom 113 (baseline haemoglobin ≥ 11 g/dl) were enrolled in the study. Linear regression analysis was used to estimate the changes in haemoglobin levels during the follow-up period. RESULTS: In a multivariate model adjusted for clinical and histopathological variables, higher interstitial fibrosis and tubular atrophy scores were more strongly associated with a decrease in haemoglobin levels than were lower scores. Compared with an interstitial fibrosis and tubular atrophy score of 0, the standardized coefficients for interstitial fibrosis and tubular atrophy scores of 1, 2 and 3 were 0.20 (95% CI -0.31 to 0.93), 0.34 (95% CI -0.22 to 1.34) and 0.47 (95% CI 0.07 to 1.96), respectively, whereas a higher glomerular class, a higher vascular lesion score and the presence of exudative lesions were not strongly correlated with the decrease in haemoglobin. CONCLUSIONS: Tubulointerstitial lesions that are more advanced are significantly associated with the progression of anaemia in patients with diabetic nephropathy after adjustment for numerous covariates. This finding suggests that tubulointerstitial lesions may be a useful prognostic indicator for anaemia in patients with diabetic nephropathy, and that decreased erythropoietin production attributable to the progression of tubulointerstitial lesions is a major cause of anaemia in these patients.