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Aging is recognized as a common risk factor for many chronic diseases and functional decline. The newly emerging field of geroscience is an interdisciplinary field that aims to understand the molecular and cellular mechanisms of aging. Several fundamental biological processes have been proposed as hallmarks of aging. The proposition of the geroscience hypothesis is that targeting holistically these highly integrated hallmarks could be an effective approach to preventing the pathogenesis of age-related diseases jointly, thereby improving the health span of most individuals. There is a growing awareness concerning the benefits of the prophylactic use of probiotics in maintaining health and improving quality of life in the elderly population. In view of the rapid progress in geroscience research, a new emphasis on geroscience-based probiotics is in high demand, and such probiotics require extensive preclinical and clinical research to support their functional efficacy. Here we propose a new term, "gerobiotics", to define those probiotic strains and their derived postbiotics and para-probiotics that are able to beneficially attenuate the fundamental mechanisms of aging, reduce physiological aging processes, and thereby expand the health span of the host. We provide a thorough discussion of why the coining of a new term is warranted instead of just referring to these probiotics as anti-aging probiotics or with other similar terms. In this review, we highlight the needs and importance of the new field of gerobiotics, past and currently on-going research and development in the field, biomarkers for potential targets, and recommended steps for the development of gerobiotic products. Use of gerobiotics could be a promising intervention strategy to improve health span and longevity of humans in the future., (©2021 BMFH Press.)

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by abdominal pain and alterations in bowel habits. Current treatments for IBS are unsatisfactory due to its multifactorial pathogenesis involving the microbiota-gut-brain axis. Lactobacillus plantarum PS128 (PS128) was reported to exhibit neuromodulatory activity which may be beneficial for improving IBS. This study aimed to investigate the effect of PS128 on visceral hypersensitivity (VH) and the gut-brain axis using a 5-hydroxytryptophan (5-HTP)-induced VH rat model without colonic inflammation induction, mimicking the characteristics of IBS. Male Sprague-Dawley rats were administered with PS128 (10 9  CFU in 0.2 mL saline/rat/day) or saline (0.2 mL saline/rat/day) for 14 days. Colorectal distension (CRD) with simultaneous electromyography recording was performed 30 min before and 30 min after the 5-HTP injection. Levels of neuropeptides and neurotrophins were analyzed. PS128 significantly reduced VH induced by the 5-HTP injection and CRD. Neurotransmitter protein levels, substance P, CGRP, BDNF, and NGF, were decreased in the dorsal root ganglion but increased in the spinal cord in response to the 5-HTP injection; PS128 reversed these changes. The hypothalamic-pituitary-adrenal axis was modulated by PS128 with decreased corticosterone concentration in serum and the expression of mineralocorticoid receptors in the amygdala. Oral administration of PS128 inhibited 5-HTP-induced VH during CRD. The ameliorative effect on VH suggests the potential application of PS128 for IBS.

We previously reported a novel psychobiotic strain of Lactobacillus plantarum PS128 (PS128) which could ameliorate anxiety-like& depression-like behaviors and modulate cerebral dopamine (DA) and serotonin (5-HT) in mice. Here, we examine the possibility of using PS128 administration to improve tic-like behaviors by using a 5-HT 2A and 5-HT 2C receptor agonist 2,5-Dimethoxy-4-iodoamphetamine (DOI). PS128 was orally administered to male Wistar rat for 2 weeks before two daily DOI injections. We recorded the behaviors immediately after the second DOI injection and compared the results with control and haloperidol treatment groups. PS128 significantly reduced tic-like behaviors and pre-pulse inhibition deficit in a threshold-dose of 10 9 CFU per day. Brain tissue analysis showed that DOI induced abnormal DA efflux in the striatum and prefrontal cortex, while PS128 ingestion improved DA metabolism and increased norepinephrine (NE) levels in these two regions. In addition, PS128 ingestion increased DA transporter and β-arrestin expressions and decreased DOI-induced phosphorylation of DA and cAMP regulated phosphoprotein of molecular weight 32 kDa (DARPP-32) at Thr34 and extracellular regulated protein kinases (ERK). PS128 ingestion also modulated peripheral 5-HT levels and shaped the cecal microbiota composition, which helps to alleviate DOI-induced dysbiosis. These results suggested that PS128 ameliorated DOI-induced tic-like hyper-active behaviors via stabilizing cerebral dopaminergic pathways through its modulation of host's microbiota-gut-brain axis. Thus, we believe there are potentials for utilizing psychobiotics to improve syndromes caused by DA dysregulation in DA-related neurological disorders and movement disorders such as Tourette syndrome., (Copyright © 2019. Published by Elsevier Inc.)

Two new computer-controlled functional tests were developed, known as the Wisconsin test battery, for carpal tunnel syndrome (CTS). The gap detection sensory test quantifies tactile thresholds for areas of the hand innervated by the median nerve. The rapid pinch and release psychomotor test measures the initiation and control of specific muscles innervated by the median nerve motor branch. Ten confirmed CTS patients (based on electrophysiological parameters and examination; 18 CTS hands) and eight confirmed normal subjects (16 hands) with a similar average age were administered both tests. The CTS patients showed significant functional deficits for both tactility and psychomotor tests. Average CTS performance was 24 to 104% poorer than for the normal subjects, depending on the performance measure. The results indicated high correlations (r = 0.5 to 0.8) between median nerve electrophysiological parameters and tactility or psychomotor performance variables. No single functional test variable had sufficient sensitivity for detecting CTS among the subject pool. The combination of the two tests using 95% confidence level cutoff points achieved a sensitivity of 0.78 and a specificity of 0.81. Stepwise discriminant analysis resulted in two performance variables capable of a sensitivity of 0.72 and a specificity of 0.94 for differentiating well-defined CTS subjects from normal subjects. Despite these promising results, limitations of the study include small sample size and subject selection bias. Further studies are needed for verifying the utility of the functional test battery for detecting CTS in a general population.

This study evaluated the Wisconsin functional sensory and psychomotor test battery for carpal tunnel syndrome (CTS). Subjects were 27 employees recruited from a food processing plant. Both hands of all subjects were examined and categorized by presence or absence of symptoms and nerve conduction study (NCS) findings (Symptom-/NCS-, Symptom+/NCS-, Symptom-/NCS+, and Symptom+/NCS+). Symptom-/NCS- category hands had significantly better performance (15-60%) for most of the functional test battery variables than Symptom+/NCS+ category hands. A significant gap detection threshold difference (32%) was observed between NCS+ and NCS- hands regardless of symptoms, with NCS- having impaired performance. No significant effect of CTS symptoms on performance was observed. Stepwise discriminant analysis was used to select the best variables to differentiate between groups. The ratio of the change in pinch rate with respect to required pinch force differentiated NCS+ from NCS- hands, with a sensitivity of 0.71 and a specificity of 0.68. The same variable had a sensitivity of 0.74 and specificity of 0.83 for distinguishing Symptom-/NCS- hands from all other categories. Pinch rate had a sensitivity of 0.82 and a specificity of 0.81 for separating Symptom+/NCS+ hands from all other categories. Use of both gap detection threshold and the ratio of the change in pinch rate with respect to required pinch force could best differentiate Symptom+/NCS+ from Symptom-/NCS- cases for a sensitivity of 0.91 and specificity of 0.87. Outcomes could not be generalized to a specific work population but demonstrate that the non-invasive test battery may be useful for providing objective measures of deficits associated with CTS symptoms and electrophysiological parameters.

Key switch design parameters, including make force, make travel, and over travel, were investigated for minimizing operator-exerted force while maximizing key-tapping speed. A mechanical apparatus was designed, constructed, and used for independently controlling key switch parameters and for directly measuring finger exertions during repetitive key tapping using strain gauge load cells. The task for the 25 participants involved using the index finger of the dominant hand to repeatedly depress a single key as rapidly as possible. Participants received visual and auditory feedback upon a successful keystroke. Peak force exerted decreased 24% and key-tapping rate increased 2% when over travel was distended from 0.0 to 3.0 mm. Although peak force exerted was not significantly affected by make point travel, key-tapping rate increased 2% when make point travel was reduced from 4.0 to 1.0 mm. These results indicate that key switch mechanisms that provide adequate over travel might enable operators to exert less force during repetitive key tapping without inhibiting performance.

An automated gap detection tactility test was investigated for quantifying sensory deficits associated with carpal tunnel syndrome (CTS). The test, which involved sensing a tiny gap in an otherwise smooth surface by probing with the finger, had functional resemblance to many work-related tactile activities such as detecting scratches or surface defects. Gap detection thresholds were measured using the converging staircase method of limits paradigm. Sixteen normal subjects between 21 and 66 years of age were tested for studying important factors affecting gap detection thresholds. Actively probing with the index finger had a threshold almost an order of magnitude more sensitive (mean = 0.19 mm, SD = 0.11 mm) than passive touch (mean = 1.63 mm, SD = 0.62 mm), which was similar to two-point discrimination. Average thresholds decreased by 24% as contact force increased from 25 to 75 g. Performance in this tactility test quickly stabilized and showed little learning effects over the period of the test, as evidenced by the lack of significant differences between six replicates. The results were highly repeatable. No significant threshold differences were observed between test and retest trials on different days, or between dominant and non-dominant hands. A contact force of 50 g was recommended as optimal for this test since it required moderate force but resulted in a smaller threshold compared with 25 or 75 g. A companion study was conducted using eight normal subjects and ten subjects diagnosed as having CTS. Average gap detection threshold, when finger probing was allowed, was 0.20 mm (SD = 0.11 min) for the normal subjects and increased two-fold to 0.40 mm (SD = 0.19 mm) for the CTS subjects. Average gap detection threshold, when the finger probing was not allowed, was 1.71 mm (SD = 0.53 mm) for the normal subjects and increased by 48% to 2.53 mm (SD = 0.87 mm) for the CTS subjects. The results suggest that people suffering from CTS may experience similar functional deficits in daily living and work activities. The small inter-subject variability makes this test a candidate for having utility as a monitoring test for loss of cutaneous tactile sensitivity.

A reliable task was developed for investigating functional deficits associated with carpal tunnel syndrome (CTS). A rapid pinch and release psychomotor task utilizing muscles of the hand innervated by the median nerve was administered using a strain gauge dynamometer and providing limited force feedback. The motor performance characteristics studied were speed and force control. An experiment was conducted for studying the effects of force level, hand dominance, test-retest reliability, learning, and inter-subject variability using 13 subjects free from any hand disabilities or symptoms. A companion study was also conducted using 17 normal subjects and ten subjects diagnosed having CTS to investigate differences between CTS and control subjects. Dominant hands performed 4% to 8% better than the non-dominant hands by having a greater pinch rate, a smaller overshoot force, and less time above the upper force level and below the lower force level. Control subjects performed 25% to 82% better than CTS subjects. Age contributed 6% of the total variance for pinch rate and 7% of the total variance for the time below the lower force level. The results suggest that people suffering from CTS may experience similar functional psychomotor deficits in daily living and manual work activities.

Psychomotor performance (PMP) involving a repeated, rapid pinch and release task was correlated with median nerve electrophysiologic parameters for control subjects (16 hands) and subjects with carpal tunnel syndrome (CTS) (14 hands). The psychomotor task was used because of its functional resemblance to many work related activities. A strain gauge dynamometer was repeatedly pinched to a predetermined force level using the index finger and thumb and then released as rapidly as possible, while measuring the actual isometric force exerted. Discrete visual and auditory feedback was provided. Median and ulnar nerve motor latencies and amplitudes, as well as median antidromic sensory latencies and amplitudes, and transcarpal latencies and amplitudes were obtained. CTS subjects had longer median motor and sensory latencies and were weaker than controls, however median motor and sensory amplitudes were not statistically different. A strong relationship was observed between electrophysiologic variables and PMP, which could not be accounted for by age differences alone. It is unclear whether the measured differences in PMP are related to sensory or motor deficits.

A ridge detection threshold task was administered to patients diagnosed as having carpal tunnel syndrome for studying performance in an occupationally relevant functional tactile inspection task. Thresholds were compared with a reference group of subjects not having carpal tunnel syndrome symptoms, performing the same task. The threshold detection task used the method of limits for studying the effects of carpal tunnel syndrome, rate of ridge height changes, ridge gradient, and direction of shearing against the skin on ridge detection thresholds for a repeated measures factorial experimental design. Sixteen carpal tunnel syndrome hands and 30 normal hands were studied. Average ridge detection threshold was 0.08 mm for the normal subjects and increased to 0.20 mm for the carpal tunnel syndrome subjects. No significant age effect was observed. These results suggest that workers having carpal tunnel syndrome may not detect an edge or surface defect in a tactile inspection task unless it was more than twice as high as detected by workers without CTS.