Acceptability of digital health technologies in early Parkinson's disease: lessons from WATCH-PD.

Introduction: Digital health technologies (DHTs) have the potential to alleviate challenges experienced in clinical trials through more objective, naturalistic, and frequent assessments of functioning. However, implementation of DHTs come with their own challenges, including acceptability and ease of use for study participants. In addition to acceptability, it is also important to understand device proficiency in the general population and within patient populations who may be asked to use DHTs for extended periods of time. We thus aimed to provide an overview of participant feedback on acceptability of DHTs, including body-worn sensors used in the clinic and a mobile application used at-home, used throughout the duration of the Wearable Assessments in the Clinic and at Home in Parkinson's Disease (WATCH-PD) study, an observational, longitudinal study looking at disease progression in early Parkinson's Disease (PD). Methods: 82 participants with PD and 50 control participants were enrolled at 17 sites throughout the United States and followed for 12 months. We assessed participants' general device proficiency at baseline, using the Mobile Device Proficiency Questionnaire (MDPQ). The mean MDPQ score at Baseline did not significantly differ between PD patients and healthy controls (20.6 [2.91] vs 21.5 [2.94], p = .10). Results: Questionnaire results demonstrated that participants had generally positive views on the comfort and use of the digital technologies throughout the duration of the study, regardless of group. Discussion: This is the first study to evaluate patient feedback and impressions of using technology in a longitudinal observational study in early Parkinson's Disease. Results demonstrate device proficiency and acceptability of various DHTs in people with Parkinson's does not differ from that of neurologically healthy older adults, and, overall, participants had a favorable view of the DHTs deployed in the WATCH-PD study.

Cryogenic spectrometer for measuring the far-IR to millimeter-wave absorptivity of cosmic analog dusts.

We report on the design, construction, and performance of a custom apparatus built to measure the frequency- and temperature-dependent absorptivity of millimeter-wave light by cosmic analog dusts. We highlight the unique challenges faced as well as a few key innovations that are part of the instrument. Among those is an ultra-compact Fourier transform spectrometer. We have measured its effective frequency range and FWHM resolution to be 150-2100 GHz and ∼45GHz, respectively. Another innovation is a cold sample positioner whose temperature can be controlled within the range of 3.7-50 K. The use of a pulse-tube cryocooler results in a pulse-synchronous signal that dominates the detector (bolometer) signal. Methods used to address that challenge are also presented.

Increased cyclooxygenase-2 (cox-2) expression and activity in a murine model of metastatic breast cancer.

Elevated prostaglandin E(2) (PGE(2)) production is a common feature of human malignancies. This activity has often been attributed to increased metabolic activity of the cyclooxygenase enzymes, although a direct comparison of these 2 parameters i.e., prostaglandin production and cox protein expression, is rarely performed in the same malignant tissue. Using a murine model of metastatic breast cancer, we show that PGE(2) levels are positively correlated with increased tumorigenic and metastatic potential. Because prostaglandin synthesis is a product of 2 isoforms of the cyclooxygenase enzyme, we examined the expression and activity of both isoforms. All tumor cell lines examined, regardless of phenotype, express both cox-1 and cox-2 proteins in vitro. In contrast to the uniform cox-2 expression in vitro, only tumors resulting from the transplantation of metastatic cell lines express cox-2 in vivo. Cox-1 is detected in both metastatic and nonmetastatic tumors. Thus, this is the first evidence that, in the tumor milieu, cox-2 expression can be regulated differently in metastatic vs. nonmetastatic lesions. Examination of PGE(2) synthesis in vitro reveals that nearly complete inhibition of prostaglandin synthesis occurs in the presence of either indomethacin, which inhibits both isoforms, or NS398, which is selective for the cox-2 isoform. Thus, even though cell lines express both isoforms, the majority of the prostaglandin synthesis stems from the activity of the inducible, cox-2 isoform. Likewise, cell growth is inhibited by both indomethacin and NS398 in a dose-dependent manner, albeit at higher drug concentrations than required to ablate PGE(2) synthesis. Despite the inhibition of prostaglandin synthesis, the cox-2 enzyme levels (protein and mRNA) were increased by either indomethacin or NS398.

Expression of the chemokines IP-10 and Mig in IL-10 transduced tumors.

Several laboratories have reported marked tumor inhibition when the cytokine interleukin-10 (IL-10) is overexpressed as a transgene in a variety of tumor cells. To identify critical effector molecules, we compared the expression of the chemokine crg-2, the murine homolog of human inducible protein 10 (human IP-10) in murine mammary tumors derived from the transplantation of six IL-10 expressing clones of tumor cell line 66.1, parental 66.1, or 66-neo-cells. We observed increased levels of IP-10 mRNA in all IL-10-expressing tumors examined in comparison to 66-neo. IP-10 mRNA was not detected in parental 66.1 tumors. The closely related chemokine Mig (monokine induced by interferon-gamma [IFN-gamma]) was also induced in all IL-10-expressing tumors. Studies of cultured tumor cells in vitro show that mammary epithelial tumor cells, in the absence of host elements, can express IP-10 and Mig in response to induction with either lipopolysaccharide (LPS) or IFN-gamma alone. The combination of LPS plus IFN-gamma resulted in even greater induction of IP-10 RNA. The kinetics of induction differ somewhat for the two chemokines, with IP-10 showing slower induction and less rapid decline. Because both Mig and IP-10 are chemotactic for tumor-infiltrating lymphocytes, we examined the presence of CD4+ and CD8+ lymphocytes in these tumors. Consistent with the upregulation of Mig and IP-10, we saw significantly increased numbers of CD8+ cells and a lesser increase in CD4+ cells in tumors with elevated levels of both chemokines.

Interleukin-10 gene transfer inhibits murine mammary tumors and elevates nitric oxide.

Transfection of cDNA for IL-10 into line 66.1 murine mammary tumor cells results in marked suppression of tumor growth and metastasis. Others have reported that nitric oxide has potent antitumor activity and IL-10 is known to regulate the inducible isoform of nitric oxide synthase (iNOS) expressed in macrophages. We identified nitric oxide production in mammary tumors as indicated by electron paramagnetic resonance detection of nitric oxide-hemoglobin (NO-Hb). IL-10 expression resulted in elevated levels of NO-Hb in mammary tumors. Immunohistochemical examination of mammary tumors for iNOS protein revealed few positively staining cells in parental or control neo-transfected tumors but strong iNOS staining in all IL-10 transfected tumors, consistent with the NO-Hb data. To determine if mammary epithelial tumor cells themselves, express nitric oxide synthase activity, cultured tumor cells were treated with pro-inflammatory cytokines and nitrite accumulation was assessed in the conditioned medium. All IL-10 producing cell lines accumulated uM concentrations of nitrite in response to short term (24 hr) cytokine stimulation. Cells not expressing IL-10 (parental and neo-transfectants) accumulated no nitrite under similar culture conditions. After longer stimulation (48 hr), parental and 66-neo cells accumulated lower amounts of nitrite. IL-10 gene transfer is associated with increased iNOS protein expression and enzymatic activity detected both in vitro and in vivo. Our findings suggest that the antimetastatic and antitumor activity of IL-10 is related to enhanced production of nitric oxide.

Age- and lobe-specific responses of the brown Norway rat prostate to androgen.

We examined the effects of age and of increasing concentrations of testosterone on the wet weight, protein content, cell number, and cell size of the ventral, dorsal, and lateral lobes of the Brown Norway rat prostate. Young (3 mo of age) and aged (15, 17, and 21 mo of age) rats received implants of increasing sizes of testosterone-filled Silastic capsules for 3 mo. Wet weights of the prostate were the same in untreated young (6-mo-old) and aged (18-24-mo-old) rats. Testosterone administration resulted in serum testosterone concentrations ranging from physiologic to superphysiologic. Dose-dependent increases in wet weights and protein contents were seen in the ventral, dorsal, and lateral prostatic lobes of both young and aged rats. For each given dose of testosterone, including doses that resulted in serum testosterone concentrations within the physiologic range, the weights and protein contents of the dorsal and lateral lobes were greater in old (24-mo-old) than in young (6-mo-old) rats, indicating an effect of age in these lobes. In contrast, ventral prostate weights and protein contents increased equivalently in young and aged rats with increasing testosterone concentration. DNA content, a measure of cell number, increased significantly in the dorsal and lateral lobes as a function of testosterone dose and age, but in the ventral lobe did not differ with testosterone dose or age. Quantitative morphologic analyses showed significant hypertrophy of epithelial cells throughout each of the three lobes in both young and aged rats treated with testosterone. Taken together, these results indicate that the prostate of Brown Norway rats shows age and lobe-specific responses to androgen with respect to wet weight, protein content, cell number, and cell morphology.

Patient care--who pays, and for what?

Economic considerations are increasingly affecting treatment strategies, particularly in illnesses such as schizophrenia, which have high degrees of morbidity and chronicity. Restrictions on the availability of public-sector hospitalization have produced increased pressure for shorter stays and more reliance on outpatient treatment. In turn, financial constraints are operative in both public- and private-sector outpatient care. Effective psychopharmacology, which involves facilitation of patient compliance, is essential to the cost-effective treatment of schizophrenic patients in the current economic climate.

The American Psychiatric Association and the Food and Drug Administration: an analysis and proposal for action.

The relationship between medicine and society is currently undergoing substantial change. While the Food and Drug Administration has no legal authority over the practicing physician, its decisions already influence medical practice. The Drug Regulation Reform Act of 1978, if passed in its present form, would grant FDA broad new powers over patient care and clinical research. In order to retain a high degree of control of its future and activities, the American Psychiatric Association must develop an effective mechanism for meeting this challenge and for serving the interests of its members and their patients. Dr. Alexander M. Schmidt comments on the author's presentation.