Interstitial cystitis-an imbalance of risk and protective factors?

Interstitial cystitis (IC) presents as a chronic pain condition with variable combinations of symptoms depending on the species and individual patient. It is diagnosed by the presence of lower urinary tract signs and symptoms in combination with a variety of comorbid health problems, a history of life adversities, and the absence of other conditions that could cause the lower urinary tract signs. IC occurs naturally in humans and cats as a dimensional condition, with patients presenting with mild, moderate, and severe symptoms. Most patients appear to recover without specific treatment. A number of rodent models of IC have been used to study its causes and treatments. Unfortunately, current therapies generally fail to ameliorate IC symptoms long-term. The recent classification of IC as a chronic primary pain disorder calls for a rethinking of current clinical and research approaches to it. Beginning when a patient encounters a clinician, precipitating, perpetuating, and palliating risk factors can be addressed until a cause or reliably effective therapy is identified, and identifying predisposing and preventive factors can inform epidemiological studies and health promotion interventions. Predisposing, precipitating, and perpetuating risk factors, including environmental, psychological, and biological, increase the activity of the central threat response system (CTRS), which plays a clinically important role in IC symptoms. Studies in cats and rodent models have revealed that environmental enrichment (EE), in the absence of bladder-directed therapies, leads to amelioration of IC symptoms, implying a central role for the CTRS in symptom precipitation and perpetuation. Conceptually moving the source of IC pain to the brain as a motivational state rather than one resulting from peripheral nociceptive input offers both clinicians and researchers novel opportunities to improve care for patients with IC and for researchers to use more ecologically valid rodent models. It may even be that IC results from an excess of risk to protective factors, making this imbalance a targetable cause rather than a consequence of IC.

Early maternal separation is not associated with changes in telomere length in domestic kittens (Felis catus).

OBJECTIVE: Studies of multiple species have found that adverse early life experiences, including childhood trauma and maternal separation, can result in accelerated telomere shortening. The objective of this study was to determine if premature separation from the mother affected telomere length in domestic kittens (Felis catus). Subjects were 42 orphaned kittens and 10 mother-reared kittens from local animal rescue groups and shelters. DNA was extracted from whole blood collected from kittens at approximately 1 week and 2 months of age. Telomere length was assessed by qPCR (quantitative polymerase chain reaction) from a total of 86 samples and expressed as a ratio of telomere PCR relative to a single copy gene PCR (T/S). RESULTS: A generalized linear mixed model found there were no detectable differences in telomere length based on survival (F 1, 76.2 = 3.35, p = 0.07), orphan status (F 1, 56.5 = 0.44, p = 0.51), time point (F 1, 43.5 = 0.19, p = 0.67), or the interaction between orphan status and time (F 1, 43.5 = 0.86, p = 0.36). Although in other species telomere shortening is commonly associated with aging, even early in life, we did not find evidence for telomere shortening by two months of age. Our results suggest that the experience of early maternal separation in domestic cats who are subsequently hand-reared by humans does not accelerate telomere shortening compared to mother-reared kittens, at least in the first few months of life.

A survey-based assessment of risk factors for cross-sucking behaviors in neonatal kittens, Felis catus.

Cross-sucking, or non-nutritive sucking on the bodies of littermates, is commonly observed in early-weaned animals. This behavior has been well-documented in production animals, which are often separated from their mothers before weaning. The behavior is less well-understood in other domestic species, such as cats (Felis catus), that can be orphaned due to neglect, maternal death, or accidental separation. Anecdotally, cross-sucking can cause injuries in kittens, sometimes severe enough to warrant euthanasia. To our knowledge, this is the first detailed study of this behavior in domestic cats. We conducted a survey of caretakers (N = 407) of kittens (< 60 days old) with the goal of identifying characteristics of individual kittens, litters, the environment, and husbandry that might be associated with the presence of cross-sucking. The final data set, representing 1358 kittens, was comprised of 301 litters experiencing sucking and 106 litters not experiencing sucking behaviors. Almost all of the kittens represented in the survey (91%) were orphaned. Results suggested that being orphaned (X 2(1) = 42.64, p < 0.001), bottle-fed (X 2(2) = 40.32, p < 0.001), younger (t(405) = 3.48 p < 0.001), separated earlier from the mother (t(376) = 3.10, p = 0.002), and being in an all-male litter (X 2(2) = 7.13, p = 0.03) increased the risks of cross-sucking. Male kittens also were more likely to be recipients of sucking behavior (X 2(1) = 32.30, p < 0.001). No clear associations between the environment or husbandry practices and the presence of sucking behavior were identified. Interruption and separation were the most frequently reported management strategies, but most kittens returned to sucking behavior when reunited. Cross-sucking is a frequently reported behavior problem in orphaned kittens that may indicate distress or poor welfare. Future research should focus on a better understanding of prevention and management strategies, and determination of the effects, if any, of cross-sucking as a kitten on adult cat outcomes or behavior.

Stress and Feline Health.

In the health sciences, stress often is defined in terms of stressors; events that are perceived as threats to one's perception of control. From this perspective, a stressor is anything that activates the central threat response system (CTRS). Recent research shows that the CTRS can be sensitized to environmental events through epigenetic modulation of gene expression. When CTRS activation is chronic, health and welfare may be harmed. Environmental modification can mitigate the harmful effects of chronic CTRS activation by reducing the individual's perception of threat and increasing its perception of control, which improves health and welfare.

Autonomic neurophysiologic implications of disorders comorbid with bladder pain syndrome vs myofascial pelvic pain.

AIMS: The neuropathophysiology of a debilitating chronic urologic pain condition, bladder pain syndrome (BPS), remains unknown. Our recent data suggests withdrawal of cardiovagal modulation in subjects with BPS, in contrast to sympathetic nervous system dysfunction in another chronic pelvic pain syndrome, myofascial pelvic pain (MPP). We evaluated whether comorbid disorders differentially associated with BPS vs MPP shed additional light on these autonomic differences. METHODS: We compared the presence and relative time of onset of 27 other medical conditions in women with BPS, MPP, both syndromes, and healthy subjects. Analysis included an adjustment for multiple comparisons. RESULTS: Among 107 female subjects (BPS alone = 32; BPS with MPP = 36; MPP alone = 9; healthy controls = 30), comorbidities differentially associated with BPS included irritable bowel syndrome (IBS), dyspepsia, and chronic nausea, whereas those associated with MPP included migraine headache and dyspepsia, consistent with the distinct autonomic neurophysiologic signatures of the two disorders. PTSD (earliest), anxiety, depression, migraine headache, fibromyalgia, chronic fatigue, and IBS usually preceded BPS or MPP. PTSD and the presence of both pelvic pain disorders in the same subject correlated with significantly increased comorbid burden. CONCLUSIONS: Our study suggests a distinct pattern of comorbid conditions in women with BPS. These findings further support our hypothesis of primary vagal defect in BPS as compared with primary sympathetic defect in MPP, suggesting a new model for chronic these pelvic pain syndromes. Chronologically, PTSD, migraine, dysmenorrhea, and IBS occurred early, supporting a role for PTSD or its trigger in the pathophysiology of chronic pelvic pain.

Chronic Lower Urinary Tract Signs in Cats: Current Understanding of Pathophysiology and Management.

Cats that present with chronic lower urinary tract signs are often diagnosed with feline idiopathic/interstitial cystitis, a disease syndrome that is more than just a bladder disease and can be associated wtih a myriad of other co-morbidities. Further, gaining a better understanding of FIC (including the most accurate descriptive terminology) may help researchers, veterinarians, pet food companies, and clients develop and tailor the best possible approaches to management of these cat's unique health and welfare needs.

Comparison of Voiding Dysfunction Phenotypes in Women with Interstitial Cystitis/Bladder Pain and Myofascial Pelvic Pain: Results from the ICEPAC Trial.

OBJECTIVE: To evaluate whether voiding parameters differ in patients with the common overlapping pelvic pain disorders, interstitial cystitis/bladder pain syndrome (IC/BPS), and myofascial pelvic pain (MPP). METHODS: Uroflow and voiding diary assessed voiding phenotypes in this prospective cohort study (ICEPAC) of women comparing IC/BPS, IC/BPS +MPP, MPP, and healthy control (HC) subjects. RESULTS: In 36 HC, 24 IC/BPS, 37 IC/BPS + MPP, and 14 MPP subjects, the voiding diary measurements indicate lower voided volumes in IC/BPS and IC/BPS + MPP groups (185 ± 24 mL, 169 ± 20 mL, respectively) compared to HC and MPP groups (294 ± 24 mL, 226 ± 36 mL, respectively; P <.05, P <.05), as well as higher 24-hour voiding frequency (11.6 ± 0.8 and 11 ± 1.2 voids/24 hours, respectively; HC 7.1 ± 0.5 voids/24 hours; P <.05, P <.05; MPP group 9 ± 1.2 voids/24 hours; P <.05, P <.05). Uroflow showed higher HC average flow rate (12.87 ± 0.92) compared to IC/BPS, IC/BPS+MPP, and MPP (8.31 ± 1.20, 8.02 ± 0.80, 8.17 ± 1.38, respectively; P <.01, P <.01, P <.05) and peak flow rate (27.0 ± 1.83) and IC/BPS, IC/BPS+MPP and MPP (16.20 ± 2.2, 17.33 ± 1.64, 17.21 ± 2.69 respectively; P <.01, P <.01, P <.05). CONCLUSION: This quantitative evaluation of voiding diary and uroflow metrics reveals distinct voiding phenotypes, which can aid in the diagnosis of chronic pelvic pain syndromes. Patients with IC/BPS had more pain with a full bladder despite similar overall pain scores. Peak and average flow rates do not provide any differentiating power between IC/BPS and MPP patients. A longer time to peak flow may favor MPP though this finding needs confirmation.

Corrigendum: Inflammation and Tissue Remodeling in the Bladder and Urethra in Feline Interstitial Cystitis.

[This corrects the article DOI: 10.3389/fnsys.2018.00013.].

Inflammation and Tissue Remodeling in the Bladder and Urethra in Feline Interstitial Cystitis.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating chronic disease of unknown etiology. A naturally occurring disease termed feline interstitial cystitis (FIC) reproduces many features of IC/BPS patients. To gain insights into mechanisms underlying IC/BPS, we investigated pathological changes in the lamina propria (LP) of the bladder and proximal urethra in cats with FIC, using histological and molecular methods. Compared to control cat tissue, we found an increased number of de-granulated mast cells, accumulation of leukocytes, increased cyclooxygenase (COX)-1 expression in the bladder LP, and increased COX-2 expression in the urethra LP from cats with FIC. We also found increased suburothelial proliferation, evidenced by mucosal von Brunn's nests, neovascularization and alterations in elastin content. Scanning electron microscopy revealed normal appearance of the superficial urethral epithelium, including the neuroendocrine cells (termed paraneurons), in FIC urethrae. Together, these histological findings suggest the presence of chronic inflammation of unknown origin leading to tissue remodeling. Since the mucosa functions as part of a "sensory network" and urothelial cells, nerves and other cells in the LP are influenced by the composition of the underlying tissues including the vasculature, the changes observed in the present study may alter the communication of sensory information between different cellular components. This type of mucosal signaling can also extend to the urethra, where recent evidence has revealed that the urethral epithelium is likely to be part of a signaling system involving paraneurons and sensory nerves. Taken together, our data suggest a more prominent role for chronic inflammation and tissue remodeling than previously thought, which may result in alterations in mucosal signaling within the urinary bladder and proximal urethra that may contribute to altered sensations and pain in cats and humans with this syndrome.

Robotic laparoendoscopic single-site benign gynecologic surgery: a single-center experience.

The da Vinci Xi surgical system was released with several upgrades and modifications compared to the previous robotic generations to facilitate minimal invasive surgery. Herein, we present our preliminary experience of robotic laparoendoscopic single-site gynecologic surgery performed for benign indications with the da Vinci Xi robotic system in a single center. Thirty-five female patients underwent robotic single-site surgery between June 2016 and January 2017. The median console time for hysterectomy with or without salpingo-oophorectomy was 41 min. The median intracorporeal vaginal cuff closure time was 18 min. Two cases (5.7%) were converted to robotic-assisted multiport surgery. There was one major intraoperative complication (2.9%). None of the patient required blood transfusion. When comparing our first 12 cases to subsequent 12 cases of R-LESS hysterectomy, there was a statistically significant decrease in surgical times and estimated blood loss. On logistic regression analysis, no association was detected between BMI and port entry time (OR 0.93, 95% CI 0.83-1.04, p = 0.23), console time (OR 0.98, 95% CI 0.94-1.02, p = 0.37), cuff closure time (OR 0.9, 95% CI 0.76-1.09, p = 0.33), operative time (OR 1, 95% CI 0.98-1.01, p = 0.97), and estimated blood loss (OR 0.98, 95% CI 0.96-1.01, p = 0.33). Our preliminary experience with robotic laparoendoscopic single-site surgery using the da Vinci Xi system has demonstrated feasibility and safety in select patients. Further studies with greater number of patients in multiple settings will help us to fully elucidate the role of da Vinci Xi surgical system in single-site gynecologic surgery.

Behavior and Welfare of Domestic Cats Housed in Cages Larger than U.S. Norm.

The effect of providing additional floor space on cat behavior and welfare is not well documented. This study involved replication of an investigation of cats' responses to enhanced cage and room environments using cages of 0.56 m2 with the same methodology but an increased space allowance of 1.1 m2. Singly housed adult cats (n = 59) were randomly assigned to a treatment group that was a combination of a managed or unmanaged room and an enriched or unenriched cage environment. Cats were observed for 2 days for maintenance, affiliative, and avoidant behaviors using scan sampling and 5-min, continuous focal sampling. At the end of Day 2, cats' reactions to the approach of an unfamiliar person were assessed. Cats housed in enriched/managed environments exhibited more maintenance and affiliative behaviors and fewer avoidant behaviors than cats in unmanaged/unenriched environments, suggesting that macro and micro environments may be equally relevant to the cat. Increased space did not enhance the cats' welfare outcomes, suggesting that the provision of additional cage space may not be as important to the cat as a managed housing environment.

Responsiveness of cats (Felidae) to silver vine (Actinidia polygama), Tatarian honeysuckle (Lonicera tatarica), valerian (Valeriana officinalis) and catnip (Nepeta cataria).

BACKGROUND: Olfactory stimulation is an often overlooked method of environmental enrichment for cats in captivity. The best known example of olfactory enrichment is the use of catnip, a plant that can cause an apparently euphoric reaction in domestic cats and most of the Pantherinae. It has long been known that some domestic cats and most tigers do not respond to catnip. Although many anecdotes exist of other plants with similar effects, data are lacking about the number of cats that respond to these plants, and if cats that do not respond to catnip respond to any of them. Furthermore, much is still unknown about which chemicals in these plants cause this response. METHODS: We tested catnip, silver vine, Tatarian honeysuckle and valerian root on 100 domestic cats and observed their response. Each cat was offered all four plant materials and a control, multiple times. Catnip and silver vine also were offered to nine tigers. The plant materials were analyzed by gas chromatography coupled with mass spectrometry to quantify concentrations of compounds believed to exert stimulating effects on cats. RESULTS: Nearly all domestic cats responded positively to olfactory enrichment. In agreement with previous studies, one out of every three cats did not respond to catnip. Almost 80% of the domestic cats responded to silver vine and about 50% to Tatarian honeysuckle and valerian root. Although cats predominantly responded to fruit galls of the silver vine plant, some also responded positively to its wood. Of the cats that did not respond to catnip, almost 75% did respond to silver vine and about one out of three to Tatarian honeysuckle. Unlike domestic cats, tigers were either not interested in silver vine or responded disapprovingly. The amount of nepetalactone was highest in catnip and only present at marginal levels in the other plants. Silver vine contained the highest concentrations of all other compounds tested. CONCLUSIONS: Olfactory enrichment for cats may have great potential. Silver vine powder from dried fruit galls and catnip were most popular among domestic cats. Silver vine and Tatarian honeysuckle appear to be good alternatives to catnip for domestic cats that do not respond to catnip.

A pilot study of health and wellness coaching for fibromyalgia.

BACKGROUND: The purpose of this study was to test the hypothesis that a health and wellness coaching (HWC)-based intervention for fibromyalgia (FM) would result in sustained improvements in health and quality of life, and reductions in health care utilization. METHODS: Nine female subjects meeting American College of Rheumatology criteria for a diagnosis of primary FM were studied. The HWC protocol had two components, which were delivered telephonically over a twelve-month period. First, each patient met individually with a coach during the 12 month study at the patient's preference of schedule and frequency (Range:22-32 × 45-min sessions). Coaches were health professionals trained in health and wellness coaching tasks, knowledge, and skills. Second, each patient participated in bimonthly (first six months) and monthly (second six months) group classes on self-coaching strategies during the 12 month study. Prior to the intervention, and after 6 months and 12 months of coaching, the Revised Fibromyalgia Impact Questionnaire (FIQR) was used to measure health and quality of life, and the Brief Pain Inventory-Short Form (BPI) was used to measure pain intensity and interference with function. Total and rheumatology-related health encounters were documented using electronic medical records. Data were analyzed using repeated measures ANOVA. RESULTS: All nine patients finished the HWC protocol. FIQR scores improved by 35 % (P = 0.001). BPI scores decreased by 32 % overall (P = 0.006), 31 % for severity (P = 0.02), and 44 % for interference (P = 0.006). Health care utilization declined by 86 % (P = 0.006) for total and 78 % (P < 0.0001) for rheumatology-related encounters. CONCLUSION: The HWC program added to standard FM therapy produced clinically significant improvements in quality of life measures (FIQR), pain (BPI), and marked reductions in health care utilization. Such improvements do not typically occur spontaneously in FM patients, suggesting that HWC deserves further consideration as an intervention for FM.

The Pelvis and Beyond: Musculoskeletal Tender Points in Women With Chronic Pelvic Pain.

OBJECTIVE: To determine the feasibility of a detailed pain sensitivity assessment using body-wide musculoskeletal tender points (TPs) in women with different types of chronic pelvic pain (CPP) and compare phenotypic differences. MATERIALS AND METHODS: Seventy women with CPP and 35 pain-free women underwent musculoskeletal evaluation of TPs in the pelvic floor, abdomen, groin, inner thigh, and all 18 fibromyalgia TPs. Patients scored elicited pain on a numeric rating scale. TP pain scores were used for intergroup comparison and intragroup correlation. RESULTS: Women with CPP were grouped as having either bladder pain syndrome (BPS, n=24) or myofascial pelvic pain (MPP, n=11) singularly or both concomitantly (BPS+MPP, n=35). TP pain scores for all evaluations were higher in women with CPP compared with healthy women (P<0.001). Women with BPS+MPP had elevated TP pain for each evaluation compared with women with BPS alone. Pelvic floor and fibromyalgia TP scores correlated strongly in the MPP group, moderately in the BPS+MPP group, and weakly in the BPS alone group. Although some moderate and strong correlations between different body locations were present in all 3 groups, only the BPS+MPP group showed moderate to strong correlations between all body TPs. CONCLUSIONS: Detailed musculoskeletal evaluation of women with CPP is feasible and well tolerated. Careful phenotyping differentiated BPS, MPP, and BPS+MPP groups. Attending to the differences between these groups clinically may lead to more effective treatment strategies and improved outcomes for patients with CPP.

Relationship between muscle sympathetic nerve activity and aortic wave reflection characteristics in aerobic- and resistance-trained subjects.

PURPOSE: Increased arterial stiffness is associated with an impairment of ventricular-vascular coupling efficiency and increased risk of cardiovascular mortality. Recently, it has been suggested that an increase in arterial stiffness is associated with resistance exercise training. Therefore, the aims of this study were to compare augmentation index (AIx) and left ventricular wasted pressure energy (LVEW) as markers of arterial stiffness and ventricular-vascular coupling efficiency in young aerobic-trained (AT) and resistance (RT)-trained subjects. We also investigated the relationship of muscle sympathetic nerve activity (MSNA) and flow-mediated dilation (FMD) to AIx in both sets of subjects to determine if endothelial function or sympathetic outflow could explain any differences in arterial stiffness. METHOD: To achieve our aims, we measured MSNA in 15 male subjects (8 RT, 7 AT) using microneurography. We also used applanation tonometry of the radial pressure waveform to noninvasively synthesize aortic pressure waveforms. FMD was calculated as percent dilation of the radial artery from baseline following a 5 min occlusion. RESULT: RT subjects had an increased AIx (12 ± 3 vs. -7 ± 2; P < 0.01), LVEW (429 ± 111 vs. -360 ± 77; P < 0.01) and MSNA burst incidence (34 ± 4 vs. 26 ± 4; P < 0.01) when compared with AT subjects. There was no difference in FMD between groups. MSNA burst incidence was also significantly related to AIx in subjects (R (2) = 0.61; P < 0.01) with a distinct demarcation between RT and AT subjects. CONCLUSION: These results confirm previous reports of a positive association between MSNA and AIx in young male resistance-trained subjects. Furthermore, RT is associated with increased arterial stiffness and elevated sympathetic outflow.

Effects of Chronic Pelvic Pain on Heart Rate Variability in Women.

PURPOSE: Interstitial cystitis/bladder pain syndrome and myofascial pelvic pain are frequently comorbid chronic pelvic pain disorders. Differences in bladder function between interstitial cystitis/bladder pain syndrome and myofascial pelvic pain suggest that efferent autonomic function may differentiate these syndromes. Heart rate variability, defined as the difference in duration of successive heartbeats, serves as an index of autonomic function by measuring its ability to modify heart rate in response to neurophysiological changes. High frequency heart rate variability was used as a reflection of more rapid vagally mediated (parasympathetic) changes. Low frequency heart rate variability signified slower fluctuations related to the baroreflex and sympathetic outflow. MATERIALS AND METHODS: Heart rate variability was derived by autoregressive frequency analysis of the continuous electrocardiogram recording of heart rate with the subject supine for 10 minutes, tilted 70 degrees with the head up for 30 minutes and supine again for 10 minutes. This institutional review board approved study included 105 female subjects, including 32 who were healthy, and 26 with interstitial cystitis/bladder pain syndrome, 12 with myofascial pelvic pain and 35 with interstitial cystitis/bladder pain syndrome plus myofascial pelvic pain. RESULTS: In all positions healthy controls had higher high frequency heart rate variability than women with interstitial cystitis/bladder pain syndrome and interstitial cystitis/bladder pain syndrome plus myofascial pelvic pain. Subjects with myofascial pelvic pain were similar to controls with greater high frequency heart rate variability at baseline (supine 1) and in upright positions than subjects with interstitial cystitis/bladder pain syndrome. Differences in low frequency heart rate variability were less evident while low-to-high frequency ratio differences appeared to be driven by the high frequency heart rate variability component. CONCLUSIONS: Subjects with interstitial cystitis/bladder pain syndrome had diminished vagal activity and a shift toward sympathetic nervous system dominance. Overall these data support the hypothesis that changes in autonomic function occur in interstitial cystitis/bladder pain syndrome but not in myofascial pelvic pain. These changes may result from interstitial cystitis/bladder pain syndrome or contribute to its pathophysiology through abnormal self-regulatory function.

Abnormalities in Expression of Structural, Barrier and Differentiation Related Proteins, and Chondroitin Sulfate in Feline and Human Interstitial Cystitis.

PURPOSE: We analyzed the urothelium of cats diagnosed with feline interstitial cystitis to determine whether abnormalities in protein expression patterns could be detected and whether the expression pattern was similar to that in patients with human interstitial cystitis/bladder pain syndrome. The proteins analyzed are involved in cell adhesion and barrier function, comprise the glycosaminoglycan layer or are differentiation markers. MATERIALS AND METHODS: Formalin fixed biopsies from 8 cats with feline interstitial cystitis and from 7 healthy control cats were labeled by immunohistochemistry and scored with a modified version of a system previously used for human samples. Cluster analysis was performed to investigate relationships between markers and samples. RESULTS: Of the feline interstitial cystitis bladders 89% showed abnormal protein expression and chondroitin sulfate patterns while only 27% of normal tissues showed slight abnormalities. Abnormalities were found in most feline interstitial cystitis samples, including biglycan in 87.5%, chondroitin sulfate, decorin, E-cadherin and keratin-20 in 100%, uroplakin in 50% and ZO-1 in 87.5%. In feline interstitial cystitis bladders about 75% of chondroitin sulfate, biglycan and decorin samples demonstrated absent luminal staining or no staining. Cluster analysis revealed that feline interstitial cystitis and normal samples could be clearly separated into 2 groups, showing that the urothelium of cats with feline interstitial cystitis is altered from normal urothelium. CONCLUSIONS: Feline interstitial cystitis produces changes in luminal glycosaminoglycan and several proteins similar to that in patients, suggesting some commonality in mechanism. Results support the use of feline interstitial cystitis as a model of human interstitial cystitis.

From FUS to Pandora syndrome: where are we, how did we get here, and where to now?

UNLABELLED: NEW CONCEPTS: Ideas about the causes of lower urinary tract signs (LUTS) in cats have changed significantly in the past 40 years. Recent research is challenging the conventional view that the bladder is always the perpetrator of LUTS, and suggests that the bladder can also be one victim of a systemic process associated with a sensitized central stress response system. AIM: In this article the authors provide their perspective on the implications of these findings for the diagnosis and treatment of cats with LUTS, provide some historical context, and suggest ways that the veterinary profession might work together to better understand the disorders underlying these signs, and possibly reduce their prevalence.

A bloodspot-based diagnostic test for fibromyalgia syndrome and related disorders.

The aim of this study was to investigate the ability of a rapid biomarker-based method for diagnosis of fibromyalgia syndrome (FM) using mid-infrared microspectroscopy (IRMS) to differentiate patients with FM from those with osteoarthritis (OA) and rheumatoid arthritis (RA), and to identify molecular species associated with the spectral patterns. Under IRB approval, blood samples were collected from patients diagnosed with FM (n = 14), RA (n = 15), or OA (n = 12). Samples were prepared, placed onto a highly reflective slide, and spectra were collected using IRMS. Spectra were analyzed using multivariate statistical modeling to differentiate groups. Aliquots of samples also were subjected to metabolomic analysis. IRMS separated subjects into classes based on spectral information with no misclassifications among FM and RA or OA patients. Interclass distances of 15.4 (FM vs. RA), 14.7 (FM vs. OA) and 2.5 (RA vs. OA) among subjects, demonstrating the ability of IRMS to achieve reliable resolution of unique spectral patterns specific to FM. Metabolomic analysis revealed that RA and OA groups were metabolically similar, whereas biochemical differences were identified in the FM that were quite distinctive from those found in the other two groups. Both IRMS and metabolomic analysis identified changes in tryptophan catabolism pathway that differentiated patients with FM from those with RA or OA.