Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, ...limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar depression; post-traumatic stress disorder), included one or more control arms, did not provide any other study-administered treatment in conjunction with ketamine (although clinically prescribed concurrent treatments were allowable), and assessed outcome using either the Montgomery-Åsberg Depression Rating Scale or the Hamilton Rating Scale for Depression (HRSD-17). Individual patient-level data for at least one outcome was obtained from 17 of 25 eligible trials pooled n = 809. Rates of participant-level data availability across 33 moderators that were solicited from these 17 studies ranged from 10.8% to 100% (median = 55.6%). After data harmonization, moderators available in at least 40% of the dataset were tested sequentially, as well as with a data-driven, combined moderator approach. Robust main effects of ketamine on acute ~24-hours; β*(95% CI) = 0.58 (0.44, 0.72); p < 0.0001 and post-acute ~7 days; β*(95% CI) = 0.38 (0.23, 0.54); p < 0.0001 depression severity were observed. Two study-level moderators emerged as significant: ketamine effects (relative to placebo) were larger in studies that required a higher degree of previous treatment resistance to federal regulatory agency-approved antidepressant medications (≥2 failed trials) for study entry; and in studies that used a crossover design. A comprehensive data-driven search for combined moderators identified statistically significant, but modest and clinically uninformative, effects (effect size r ≤ 0.29, a small-medium effect). Ketamine robustly reduces depressive symptoms in a heterogeneous range of patients, with benefit relative to placebo even greater in patients more resistant to prior medications. In this largest effort to date to apply precision medicine approaches to ketamine treatment, no clinical or demographic patient-level features were detected that could be used to guide ketamine treatment decisions.Review Registration: PROSPERO Identifier: CRD42021235630.
•Process demonstrated for integration of ZnO TFTs with a PZT thin film.•Piezoelectric response shown to be controllable via ZnO array electronics.•Integrated electronics with piezoelectrics is a ...viable solution for adaptive optics.
Direct integration of electronics on piezoelectrics is attractive for large array transducers and adjustable optics systems; it allows for the possibility of reconfigurability as well as active surfaces with a greatly reduced number of electrical connections. In this work, lead zirconate titanate (PZT) piezoelectric films were co-processed with ZnO thin film transistors to explore the possibility of direct integration. The sputter deposited PZT on glass had good electrical properties on large area (cm2) electrodes, with a dielectric constant of >1200 with a loss of approximately 2% and an average remanent polarization of greater than >23 μC/cm2. Fabrication of arrays of thin film transistors (TFTs) processed directly on top of PZT pixels for use in an adaptive optics system was demonstrated. Photoreactive benzocyclobutene (BCB) electrically isolated the ZnO TFTs, deposited using plasma enhanced atomic layer deposition, from the electrodes on the piezoelectric cell. Flex cables were bonded to the wafer using anisotropic conductive film (ACF) to connect the gates (row control) and the drains (column control) in the TFT array to a control box. It was found that when actuating the PZT cells through the TFT array with 5–10 V, the glass mirror experienced approximately 700–1000 nm of deflection, adequate for figure control in future X-ray mirrors.
Abstract Background The pathways to increased cardiovascular risk in bipolar disorder include health behaviors, psychosocial stress and long-term medication exposure. However, the evidence that the ...association between cardiovascular risk factors and bipolar disorder remains significant after controlling for these co-factors suggests that additional important risk factors have yet to be identified. Our hypothesis is that disturbances in the sleep-wake cycle are an important and under-recognized pathway through which affective disorders lead to increased cardiovascular risk. Methods In patients with bipolar disorder type 1 in clinical remission, we: 1) explored whether sleep disturbance predicted the endorsement of NCEP ATP-III criteria for dyslipidemia, independent of other lifestyle factors and 2) tested the association between low HDL (NCEP-ATP III) and sleep duration measured with actigraphy over an eight-day period. Results Median sleep duration is significantly associated with low HDL. The risk of having low HDL increases by 1.23 with every 30 minutes of reduced sleep time. Limitations Since sleep patterns in patients with bipolar disorder are variable and irregular, it is possible that other sleep characteristics, not present during the span of our study, or the variability itself may be what drives the increased cardiovascular risk. Conclusions Sleep characteristics of patients with bipolar disorder in clinical remission are associated with cardiovascular risk. More specifically, sleep duration was associated with low HDL. Clinicians should pay special attention to sleep hygiene in treating individuals with bipolar disorder, even when they are in clinical remission.
To reveal sleep health phenotypes in older adults and examine their associations with time to 5-year all-cause and cardiovascular mortality.
Prospective longitudinal cohorts.
The Study of ...Osteoporotic Fractures and Outcomes of Sleep Disorders in Older Men Study.
N = 1722 men and women aged ≥65 years matched 1:1 on sociodemographic and clinical measures.
Self-reported habitual sleep health characteristics (satisfaction, daytime sleepiness, timing, efficiency, and duration) measured at an initial visit and longitudinal follow-up for mortality.
Latent class analysis revealed 3 sleep health phenotypes: (1) heightened sleep propensity (HSP; medium to long duration, high sleepiness, high efficiency/satisfaction; n = 322), (2) average sleep (AS; medium duration, average efficiency, high satisfaction, low sleepiness; n = 1,109), and (3) insomnia with short sleep (ISS; short to medium duration, low efficiency/satisfaction, moderate sleepiness; n = 291). Phenotype predicted time to all-cause mortality (χ2 = 9.4, P = .01), with HSP conferring greater risk than AS (hazard ratio 95% confidence interval = 1.48 1.15-1.92) or ISS (1.52 1.07-2.17), despite ISS reporting the poorest mental and physical health. Although sex did not formally moderate the relationship between phenotype and mortality, subgroup analyses indicated that these findings were driven primarily by women. Phenotype did not predict cardiovascular mortality.
These analyses support the utility of examining multidimensional sleep health profiles by suggesting that the combination of long sleep, high efficiency/satisfaction, and daytime sleepiness—previously identified as independent risk factors—may be components of a single high-risk sleep phenotype, HSP. Further investigation of sex differences and the mechanisms underlying mortality risk associated with HSP is warranted.
A 6‐year‐old, male neutered mixed breed dog was presented emergently with a three‐week history of hyporexia, vomiting, diarrhoea and weight loss. Upon examination, the patient was dull, had ...generalised muscle atrophy, moderate abdominal pain and a mild amount of peritoneal effusion. A fluid‐filled, distended, corrugated small bowel with marked gastroparesis and moderate peritoneal effusion was noted on abdominal ultrasonography. Endoscopy revealed hyperaemic and friable mucosa and a subjectively narrowed pylorus. Emergency exploratory celiotomy was performed due to worsening patient condition and revealed thick, diffuse, fibrous adhesions of the abdominal cavity. Based on these findings, sclerosing encapsulating peritonitis (SEP) was suspected. A large mass of omentum adjacent to the greater curvature of the stomach had caused a pyloric outflow obstruction. Adhesiolysis was attempted but was unsuccessful due to the friability of the small intestines. The dog was humanely euthanased under anaesthesia. A diagnosis of SEP was confirmed via necropsy. No underlying cause was identified. This is the first known case of a pyloric outflow obstruction secondary to SEP in a dog. Although rare, this condition should be considered as a differential for dogs with signs of a pyloric outflow obstruction with concurrent ascites and abdominal pain, hyporexia, vomiting and diarrhoea.
Immunopathology continues to be important in diagnostic dermatopathology. Immunopathologyis an invaluable tool for assessing the tissue of origin or direction of differentiation of cells. In some ...cases this can result in a more precise diagnosis. This article reviews the role of immunopathology in determining the biologic behavior of hematolymphoid infiltrates. It explores the methodology of immunoperoxidase, discusses the most commonly used antibody reagents, and presents a series of diagnostic dilemmas in which immunopathology can be useful. In each case a strategy is established that maximizes the likelihood of making a definitive diagnosis.
Ezetimibe and Simvastatin Reduce Inflammation, Disease Activity, Aortic Stiffness and Improve Endothelial Function in Rheumatoid Arthritis Kaisa M. Mäki-Petäjä, Anthony D. Booth, Frances C. Hall, ...Sharon M. L. Wallace, John Brown, Carmel M. McEniery, Ian B. Wilkinson This study demonstrates that both ezetimibe and simvastatin reduce disease activity, inflammatory markers, and aortic pulse wave velocity and improve endothelial function in patients with rheumatoid arthritis (RA). These results suggest that the reduction of cholesterol per se ameliorates aortic stiffness and endothelial dysfunction. The data indicate that cholesterol-reducing therapies may be beneficial for RA patients, because they are well tolerated, improve clinical outcome, and reduce surrogates of cardiovascular risk.
Syringomas may be at least partially under estrogen and/or progesterone influence, as they are more common in women and are known to proliferate at puberty. During pregnancy and the premenstrual ...period an increase in tumor size has also been described. We examined nine syringomas using immunohistochemical markers for estrogen (ER) and progesterone (PR) receptors. Scattered tumor cells displaying nuclear and cytoplasmic staining for ER were noted in one of the nine cases. Intense nuclear and cytoplasmic staining for PR was noted in most (> 80%) of the neoplastic cells in 8/9 syringoma cases. Current immunohistochemical evidence supports the theory that syringomas are under hormonal control.
Methodological Approaches to Optimize Reproducibility and Power in Clinical Studies of Flow-Mediated Dilation Ann E. Donald, Julian P. Halcox, Marietta Charakida, Clare Storry, Sharon M. L. Wallace, ...Tim J. Cole, Peter Friberg, John E. Deanfield We assessed the reproducibility of components of the flow-mediated dilation (FMD) response and their ability to discriminate between health and disease. The peak FMD was the most reproducible. All components except the time to peak were significantly lower in subjects with risk factors. Power curves generated from these results can be used to inform on the appropriate number of subjects for clinical trials.
In some situations, hair growth is under hormonal control. Androgenic alopecia is characterized as hormonally driven hair loss in the genetically susceptible individual. During pregnancy, hair growth ...is increased, as estrogen appears to prolong the anagen phase. However, postpartum hair loss is common, and thus may be related to a decrease in estrogen and or progesterone levels. In contrast, alopecia areata is not considered to be under hormonal control. We compared the immunohistochemical staining characteristics of nine cases of androgenic alopecia with those of 13 cases of alopecia areata using estrogen receptor (ER) and progesterone receptor (PR) markers. Estrogen receptor positivity in the dermal papilla was found in only two of 13 cases of alopecia areata, and in one case of androgenic alopecia. Six of 13 cases of alopecia areata demonstrated focal reactivity with the progesterone marker in a similar location, while only three cases of androgenic alopecia showed positivity with this antibody. Examination of the perifollicular fibroblasts for the ER marker showed positivity in one of 13 cases of alopecia areata and in one case of androgenic alopecia. Two cases of alopecia areata revealed focal staining in this location for the PR marker, while the androgenic alopecia cases failed to stain. These results indicate that estrogen and progesterone receptor expression is not significantly increased or decreased in the pilosebaceous units or surrounding mesenchymal cells in androgenic alopecia vs. alopecia areata. Therefore, an indirectly mediated process of estrogen/progesterone control on hair growth and development must be presumed for cases of androgenic alopecia.
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