Stress and loneliness are biologically toxic factors with adverse effects on mental and physical health. The 2018 Gallup World Poll found a 25%–40% increase in stress, worry, and anger in the US from 2008 to 2018. Loneliness is associated with considerable distress, and older adults are vulnerable to loneliness due to losses, physical decline, and social isolation. The COVID-19 pandemic led to increased social isolation, though some older adults with higher levels of resilience and wisdom faced the pandemic with greater fortitude than younger adults.Aging is associated with numerous stressors that negatively impact older adults’ well-being. Resilience improves ability to cope with stressors and can be enhanced in older adults. Senior housing communities are promising settings to deliver positive psychiatry interventions due to rising resident populations and potential impact of delivering interventions directly in the community. 

Contact force is a natural way for humans to interact with the physical world around us. However, most of our interactions with the digital world are largely based on a simple binary sense of touch (contact or no contact). Similarly, when interacting with robots to perform complex tasks, such as surgery, we need to acquire the rich force information and contact location, to aid in the task. To address these issues, researchers at UC San Diego have developed WiForce, which is a ‘wireless’ sensor that can be attached to an object or robot, like a sticker. WiForce’s sensor transduces force magnitude and location into phase changes of an incident RF signal, which is reflected back to enable measurement of force and contact location.

Older adults commonly experience stressors related to a decline in physical, cognitive, and functional abilities, loss of purpose and independence, bereavement, societal ageism, and financial hardships. Chronic stressors have cascading effects on physical and mental outcomes, including worse overall well-being, increased depression, and greater physical disability and mobility limitation. Stressful events increase the likelihood of chronic metabolic, pulmonary, and cardiovascular diseases. These stressors are often unavoidable in modern Western societies, given the realities of aging, so identifying methods to enhance older adults’ ability to manage stressors is essential. 

Schistosomiasis is a disease caused by infection with parasitic flatworms called schistosomes. The three major medically important species are Schistosoma mansoni (causing intestinal schistosomiasis in Africa and South America), S. japonicum (intestinal schistosomiasis in East Asia), and S. haematobium (causing genitourinary schistosomiasis in Africa and the Middle East). Signs and symptoms may include abdominal pain, diarrhea, bloody stool, or blood in the urine.  The treatment of schistosomiasis serves three purposes: reversing acute or early chronic disease, preventing complications associated with chronic infection, and preventing neuroschistosomiasis. The goal of treatment is to remove the worms that produce the eggs which, in turn, are responsible for disease morbidity and mortality. There is no effective vaccine against schistosomiasis.

NMDA receptors (NMDARs) are principal regulators of synaptic signaling in the brain. Modulation of NMDARs’ function and trafficking is important for the regulation of synaptic transmission and several forms of synaptic plasticity. Postsynaptic density protein 95 (PSD-95) acts as a scaffolding protein and stabilizes the surface and synaptic expression of NMDARs. NMDA receptors (NMDARs) are ionotropic glutamate receptors that are expressed throughout the nervous system and play crucial roles in neuronal development, synaptic plasticity, learning and memory. PSD-95 (Post Synaptic Density protein) or SAP90, a membrane-associated guanylate kinase (MAGUK), is the major scaffolding protein in the excitatory postsynaptic density (PSD) and a potent regulator of synaptic strength. It is almost exclusively located in the post synaptic density of neurons and is involved in anchoring synaptic proteins. Its direct and indirect binding partners include neuroligin, NMDA receptors, AMPA receptors, and potassium channels. Postsynaptic loss does not precede obvious Aβ (beta-amyloid or amyloid beta) and Tau deposition, but instead appears to occur as Aβ and Tau pathologies advance. This indicates that PSD-95 is an excellent intrinsic biomarker for post synaptic mechanisms and its expression is reduced in brain tissue from patients with Alzheimer’s Disease (AD) as well as in mouse models of AD.

Uveal melanoma commonly known as ocular or choroidal melanoma, is a rare cancer of the eye. It is an intraocular malignancy that arises from melanocytes of the choroid, ciliary body, and iris of the eye. Ocular melanoma is diagnosed in approximately 2,000-2,500 adults annually in the United States. In both the U.S. and Europe, this equates to about 5 - 7.5 cases per million people per year and, for people over 50 years old, the incidence rate increases to around 21 per million per year. While the primary tumor is highly treatable, about half of the patients will develop metastasis —typically to the liver. Metastatic disease is universally fatal. While traditional staging methods such as tumor size and location, still play a role in assessing metastatic risk, they are rarely used to individualize patient management plans. Newer methods include chromosomal gene expression analysis, yet these methods have their technical limitations. Clearly, what is needed is a better, cheaper and reproducible prognostic test.

Certain pesticides can be harmful, and there is a need for effective antidotes that can reverse accidental over-exposure by farm workers. UC San Diego researchers have recently developed a therapeutic modality that is a combination of compositions that may be effective as an antidote.

Cyanide is a rapidly acting poison, which, along with carbon monoxide, is the major cause of death from smoke inhalation. For treating a large number of casulaties in the field, the best mode of treatment would be intramuscular injection of antidote, preferably by an autoinjector. The two treatments currently approved for cyanide poisoning— hydroxocobalamin (Cyanokit) and the combination of sodium nitrite and sodium thiosulfate (Nithiodote)—must be administered by intravenous injection. Thus, no agent currently exists for rapidly treating a large number of cyanide poisoned persons. Another rapidly acting poison similar to cyanide, is hydrogen sulfide. People are exposed to hydrogen sulfide gas in a variety of occupations, most notably wastewater processing, and agriculture and petroleum industries. Up to 30% of oil workers have been exposed to sufficient amounts of hydrogen sulfide to have symptoms, and fatalities are not uncommon. No specific treatment currently exists for sulfide poisoning, and treatment consists of general supportive care.

Natural killer (NK) cells are a key component of the innate immune system and are involved in early defense against viruses and cancer cells. NK cells have the ability to lyse cells without prior sensitization  and therefore are the subject of intense interest to be potentially used as immunotherapeutic targets to treat cancer. The crucial element for using NK cells in immunotherapy is the ability to control the signaling and activation pathways. Recent work has shown that the cytokine-inducible SH2-containing protein (CIS), encoded by the Cish gene, can act as a checkpoint in NK activation by inhibiting IL-15 signaling, a major upregulator of NK cell activity. Furthermore, deletion of the Cish gene has been shown to increase the sensitivity of NK cells to IL-15, resulting in mice that are resistant to experimental metastasis.

Cyanide is a highly toxic agent that inhibits mitochondrial cytochrome-c oxidase, thereby depleting cellular ATP. Cyanide exposure contributes to smoke inhalation deaths in fires and could be used as a weapon of mass destruction. Cobalamin (vitamin B12) binds cyanide with a relatively high affinity and is used to treat smoke inhalation victims. Cobinamide, the penultimate compound in cobalamin biosynthesis, binds cyanide with about 1010 greater affinity than cobalamin and is 5-10 times more potent than cobalamin in rescuing animals from cyanide poisoning. Cobinamide is also an effective intra- and extracellular nitric oxide scavenger. Currently, three cyanide antidotes are currently available in the United States: nitrites, thiosulfate, and hydroxocobalamin. All three drugs are approved only for intravenous (IV) administration, and thus are not suitable for treating mass casualties as could occur after a major industrial accident or a terrorist attack. Thus, new formulations for cyanide exposure treatment that are faster and easier to administer are needed.

In the United States lives are lost every year due to the spread of infections in hospitals and healthcare facilities. Thus, healthcare workers must take all precautions to prevent the spread of infectious diseases, especially in surgical spaces. One key step in this process is to control environmental surfaces because certain types of microbial bacteria or fungi are capable of surviving on environmental surfaces for months at a time. A potential solution would be to use consumables that are disposable, or semi-disposable, and offer a platform of products for the purposes of infection control.  

Angioedema is a non-itchy, pale swelling of subcutaneous or submucosal tissue that tends to recur chronically and can become life-threatening if the swelling occurs in the upper airways or can be very painful if it occurs in the gastrointestinal tract. Angioedema presenting together with urticarial (hives) usually responds well to antihistamines and corticosteroids, whereas angioedema without urticarial (hives) is frequently resistant to such therapy but may respond to a C1 esterase inhibitor, tranexamic acid, or both therapies that can reduce bradykinin generation. Differentiating bradykinin-from histamine-mediated angioedema is of critical importance to prevent morbidity and mortality. The ability to diagnose bradykinin-mediated angioedema with normal C1 inhibitor (C1INH), however has been severely limited by the lack of any available diagnostic test. Current genetic tests only identify a tiny fraction of the affected patients. Due to the lack of a known biomarker or assay, many patients without bradykinin-mediated angioedema are treated with unnecessary medications (often approaching $1,000,000/year or more in costs).

Training for direct laryngoscopy relies heavily on practice with patients. The necessity for human practice might be supplanted to some extent by an intubation manikin with accurate airway anatomy, a realistic “feel” during laryngoscopy, the capacity to model many patient configurations, and a means to provide feedback to trainees and instructors. The realism and mobility of the anatomical features of current models limits the effectiveness of training intubation skills. Current models provide only one set of anatomic features, but patients present innumerable combinations of size, shape, proportion, and tissue stiffness. Thus, a novice who trains on a particular model merely learns how to intubate that particular model, but has minimal ability to transfer the learned skills to the multiplicity of anatomies in patients. Furthermore, most models approximate a normal anatomic configuration that poses no problem for intubation, so novices do not gain experience with difficult situations

Neurodegenerative disorders with Tau accumulation are a common cause of dementia in the aging population. Alzheimer’s Disease (AD), Pick’s Disease (PiD) and Fronto-temporal lobar degeneration (FTLD) are examples of neurodegenerative disorders with Tau accumulation and are also jointly referred as “taupathies”. Tauopathies are a group of neurodegenerative disorders with accumulation of three-repeat (3R) or four-repeat (4R) Tau. While 3R tau is found in Pick's disease and Alzheimer's disease (AD), 4R tau is more abundant in corticobasal degeneration, progressive supranuclear palsy, and AD.

Synthetic polymer constructs are an important tool in modern medical practice, but the lack of control over their activity limits their utility. The ability to combine structural function with localized interaction has proven extremely successful in stents, but polymer technology has not advanced sufficiently to serve a wider range of needs. PLGA polyesters can be degraded by hydrolysis facilitating their widespread use in medicine and biomedical research. Their dependence on slow hydrolysis makes for long degradation times (half-life of one year in vivo) limiting their applicability. While degradation can be sped up by copolymerization with more hydrophilic monomers; degradation is still too slow for triggered release or degradation.

Excessive hair disorders (hypertrichosis, hirsutism) can have severe impact on an individual's self-esteem and ability to interact successfully in the workplace and social settings.  Existing therapies, with a potential for long-term hair removal, include laser therapy and/or electrolysis.  These require multiple courses, are expensive and may not be fully or permanently effective.  While hirsutism may respond to medical/hormonal therapies, such as oral contraceptive pills (OCPs), glucocorticoids, or antiandrogens such as spironolactone, these often have adverse side effects such as fatigue, pain, weight gain, depression.  Furthermore, many patients find that they still require laser or electrolysis in addition to medical therapy.  Therefore there is a large unmet need for safe, simple and cost-effective treatments for hypertrichosis.

Nerve injury in the Peripheral Nervous System is caused by trauma, vehicular accidents, repetitive stress, and wartime injuries and affects up to 1% of the U.S. population by age 70. Severed nerves lead to severe pain or the lack of sensation and mobility.

Drug clearance is the important process by which a drug and/or its metabolites are eliminated from an organism.  When drug clearance is excessive, efficacy of the drug may not be achieved; when drug clearance is inadequate, toxicity to the organism may result.  Members of the solute carrier (SLC) and ATP-binding cassette (ABC) “drug” transporter families  have  well-established roles in absorbing, distributing, and eliminating xenobiotics such as drugs. In addition, there is growing evidence for suggesting that these transporters also transport metabolites, nutrients, signaling molecules, and antioxidants at the organismal and cellular levels. Competition of drugs with metabolites at the level of transporters involved in absorption, distribution, and elimination of drugs and metabolites can lead to major metabolic side effects over the long term.  Owing to the tremendous clinical importance of these transporters, there is a need to combine metabolic reconstruction (systems biology) methods with computational (pharmaceutical) chemistry, as well as wet lab validation to study these transporters of the SLC and ABC family and drug-induced metabolic changes.

High frequency data collection in a participant’s usual environment (ecological momentary assessment, or EMA) offers a promising approach for understanding, and potentially intervening on, the precursors of clinically important states and behaviors in mental health disorders.  

Identification and evaluation of new therapeutic agents and the identification of suspected disease targets (which typically employ animal models) are expensive, time consuming, etc.  In vitro alternatives have relied on the use of conventional cell culture systems which are limited in that they do not allow the three-dimensional interactions that occur between cells and their surrounding tissue. Additionally, cells not only sense and respond to chemical cues, they also respond to the physical environments. 

Exposure to organophosphates (OP) from both pesticides and nerve agents leads to inhibition of acetylcholinesterase (AChE), resulting in a build-up of acetylcholine in the body, and potentially death. The only OP stoichiometric bioscavenger in use today is butyrylcholinesterase (hBChE). Human butylcholinesterase (hBChE) specifically and efficiently captures offending OP molecules in the circulation of exposed individuals, sequestering the OP as an inactive conjugate in the plasma.

Many institutions are implementing anal cancer screening programs modeled on procedures used in cervical cancer. Analogous to cervical colposcopy screening procedures, the high resolution anoscopy (HRA) poses additional challenges due to unique characteristics of the procedure. This includes the uneven topography and collapsing nature of anal canal, making it a more challenging procedure than cervical colposcopy. Additionally, there is considerable variability in how HRA providers position the patient and document the position of visualized lesions. HRA practitioners about to perform a HRA follow-up examination or ablative treatment typically review prior HRA images saved in free-standing image management software (i.e. image files are generally not linked to electronic medicaI record systems). With these current limitations, there exists a need for a method to standardize how HRA results are documented in the medical record.

Matrix metalloproteinases (MMPs) as well as other proteases play a crucial role in cancer invasion and metastasis. Increase in MMP levels correlate with higher stage, increased cancer grade and higher activity when overexpressed in malignant tumors and is associated with poorer patient prognosis. The expression of proteases in clinical tumors has been studied through measurement of mRNA levels and immunoassays.  These techniques monitor the sum of all forms of the protease, much of which is either inactive proenzyme or inactive complexes that have endogenous inhibitor proteins (e.g. TIMPs). Recent methods for detection such as “in situ zymography” is slow and qualitative.   The ability to accurately measure and/or monitor the active enzyme in a patient’s tumor could provide improved intra-operative imaging of tumor margins by utilizing a fluorescent probe which is specific for the tumor’s protease(s).  Obtaining the expression profile of tissue excised during surgery could aid with the assessment of post-surgical options.

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Tissue engineering has recently focused on biomimetic matrices, usually polymer hydrogels, that include multiple layers with distinct structures and chemical components. Current methods of fabricating such matrices are complex or expensive to implement and often produce mechanical weaknesses between layers. Thus, an adaptable, facile, and economical multilayer polymer fabrication technique that produces continuous interfaces between layers is needed.