Next-generation precision medicine for suicidality prevention.

Suicidality remains a clear and present danger in society in general, and for mental health patients in particular. Lack of widespread use of objective and/or quantitative information has hampered treatment and prevention efforts. Suicidality is a spectrum of severity from vague thoughts that life is not worth living, to ideation, plans, attempts, and completion. Blood biomarkers that track suicidality risk provide a window into the biology of suicidality, as well as could help with assessment and treatment. Previous studies by us were positive. Here we describe new studies we conducted transdiagnostically in psychiatric patients, starting with the whole genome, to expand the identification, prioritization, validation and testing of blood gene expression biomarkers for suicidality, using a multiple independent cohorts design. We found new as well as previously known biomarkers that were predictive of high suicidality states, and of future psychiatric hospitalizations related to them, using cross-sectional and longitudinal approaches. The overall top increased in expression biomarker was SLC6A4, the serotonin transporter. The top decreased biomarker was TINF2, a gene whose mutations result in very short telomeres. The top biological pathways were related to apoptosis. The top upstream regulator was prednisolone. Taken together, our data supports the possibility that biologically, suicidality is an extreme stress-driven form of active aging/death. Consistent with that, the top subtypes of suicidality identified by us just based on clinical measures had high stress and high anxiety. Top therapeutic matches overall were lithium, clozapine and ketamine, with lithium stronger in females and clozapine stronger in males. Drug repurposing bioinformatic analyses identified the potential of renin-angiotensin system modulators and of cyclooxygenase inhibitors. Additionally, we show how patient reports for doctors would look based on blood biomarkers testing, personalized by gender. We also integrated with the blood biomarker testing social determinants and psychological measures (CFI-S, suicidal ideation), showing synergy. Lastly, we compared that to machine learning approaches, to optimize predictive ability and identify key features. We propose that our findings and comprehensive approach can have transformative clinical utility.

Decontaminating infectious laboratory waste by autoclaving.

The temperature profile of infectious laboratory waste being autoclaved was examined relative to the type of containers used in the process. A standardized waste load (1,750 +/- 4 g) placed in the container was evaluated by using a direct readout thermocouple. The sensor of the thermocouple was placed within an unused and outdated agar plate, centrally located about 5 cm from the bottom of the container. The gravity displacement autoclave tested reached 121 degrees C within 3 min. Waste within a steel container (plus 1 liter of water) reached 108, 120, and 122 degrees C at 12, 30, and 50 min, respectively. Without the addition of water, the corresponding temperatures were 60, 110, and 120 degrees C, respectively. With a steel container, "autoclavable" plastic bags, and no additional water, the temperatures were 36, 71, and 105 degrees C, respectively. When 1 liter of water was placed in the autoclavable bag, the temperatures were 98, 115, and 121 degrees C, respectively. Waste within a polypropylene container (dimensions similar to those of the steel container) with and without the addition of 1 liter of water, reached a maximum temperature of 108 degrees C at 50 min. With a polypropylene container, autoclavable plastic bag, and 1 liter of water, the corresponding temperature was 99 degrees C. Without the addition of water, the temperature was 92 degrees C. The importance of container, moisture, and material in autoclaving was demonstrated.

Wash water temperature and sanitation in the hospital laundry.

In view of energy shortages and high costs for heating water in hospitals for laundering, the advantages and disadvantages of using lower temperature water are explored. Including are discussions of cleaning power of water, detergents and bleaches, and microbial removal using a temperature range of 38 to 74 degrees C.

Immunosuppressive lymphocyte factors: characterization of the IDS-producing cell in the experimental model of antigenic competition.

Inhibitor of DNA synthesis, is a soluble, protein lymphocyte factor which nonspecifically suppresses in vitro lymphocyte responses to antigens or mitogens. It is secreted in large amounts in vivo in some experimentally induced immunological paralysis. Here, we have defined the cell secreting IDS in one experimental model of non-specific immune-suppression, ie., that of antigenic competition. Lymphocytes of rats injected with a large dose of ovalbumin intravenously, show no immunologic response to the same or other antigens or mitogens 24 hr later. At this time, spleen cells of these rats secrete large amounts of the inhibitor into culture supernatants. However spleen cell supernatants of T-depleted rats do not contain the activity. Further, maximal inhibitor concentrations are obtained in the first 2 days of culture when more than 65% of cultured cells are large blasts actively synthesizing protein. As the number of actively metabolizing blast cells decrease in subsequent days of culture inhibitor concentration falls. Finally thymocytes of rats pretreated with hydrocortisone acetate, to deplete thymus cortex cells are unable to secrete inhibitor in culture. These findings reveal that the cells producing inhibitory DNA synthesis in an animal made tolerant with a supra-optimal dose of antigen is an active blast transformed T cell (present in the spleen and thymus). In the thymus the cell making inhibitor appears to reside in the thymus cortex. Previous experiments have confirmed that an identical cell causes nonspecific immune-suppression in vitro. We suggest that this cell produces in vivo tolerance in antigenic competition through the release of inhibitor to DNA synthesis.

Immuno-suppressive lymphocyte factors. I. Purification of inhibitor of DNA synthesis to homogeneity.

Inhibitor of DNA synthesis (IDS) is a T-lymphocyte factor, whose role in immunnoregulation might be to nonspecifically suppress the immune system especially in situations where very high, prolonged tolerogenic doses of antigens are present. We have purified IDS-contained supernates of stimulated lymphocytes to homogeneity, through isoelectric focusing and Sephadex gel chromatography. IDS has an isoelectric point of 2.73-2.75 and in its monomeric form has a mol wt of 20,000 but exists in the supernate usually as an aggregated tetrameric form. Di- and trimeric forms are also seen. All forms are biologically active. Purity was confirmed by SDS gel electrophoresis and the binding of dansyl chloride to terminal or free amino groups of proteins and peptides. We have, further confirmed that pure IDS is not cytotoxic and is probably a glycoprotein whose activity depends on an intact carbohydrate moiety.

Energy expenditure for thermoregulation and locomotion in emperor penguins.

During the antarctic winter emperor penguins (Aptenodytes forsteri) spend up to four mo fasting while they breed at rookeries 80 km or more from the sea, huddling close together in the cold. This breeding cycle makes exceptional demands on their energy reserves, and we therefore studied their thermoregulation and locomotion. Rates of metabolism were measured in five birds (mean body mass, 23.37 kg) at ambient temperatures ranging from 25 to -47 degrees C. Between 20 and -10 degrees C the metabolic rate (standard metabolic rate (SMR)) remained neraly constant, about 42.9 W. Below -10 degrees C metabolic rate increased lineraly with decreasing ambient temperature and at -47 degrees C it was 70% above the SMR. Mean thermal conductance below -10 degrees C was 1.57 W m-2 degrees C-1. Metabolic rate during treadmill walking increased linearly with increasing speed. Our data suggest that walking 200 km (from the sea to the rookery and back) requires less than 15% of the energy reserves of a breeding male emperor penguin initially weighing 35 kg. The high energy requirement for thermoregulation (about 85%) would, in the absence of huddling, probably exceed the total energy reserves.