Complaints of abnormal foot temperature are common among patients with polyneuropathy. However, there is no published method of ambulatory foot temperature measurement to identify possible thermoregulatory disturbances in these patients. We configured a digital electronic thermometer and thermocouple to measure and record distal foot and ambient temperatures simultaneously every minute for 24 to 48 h. Sixteen patients with polyneuropathy and 5 normal subjects were studied; 12 patients with polyneuropathy and 4 normal subjects had at least 24 h of successful recording. The data obtained from these patients were consistent and easily summarized by standard statistical methods. In the others, technical difficulties produced nonphysiological readings. In the patients with polyneuropathy, changes in foot temperature mirrored ambient temperature fluctuations more closely than in normal subjects. This technique shows promise in studying temperature regulation in the feet and may provide new insights into neuropathy-associated pain and the pathogenesis of polyneuropathy.
Abstract Background : This study focuses on factors that may disproportionately affect female veterans’ mental health, compared to men, and is part of a larger study assessing the prevalence of mental health disorders and treatment seeking among formerly deployed US military service members. Methods : We surveyed a random sample of 1,730 veterans who were patients in a large non-VA hospital system in the US. Based on previous research, women were hypothesized to be at higher risk for psychological problems. We adjusted our results for confounding factors, including history of trauma, childhood abuse, combat exposure, deployments, stressful life events, alcohol misuse, psychological resources, and social support. Results : Among the veterans studied, 5% were female (n=85), 96% were White (n=1,161), 22.9% were Iraq/Afghanistan veterans (n=398), and the mean age was 59 years old (SD=12). Compared to males, female veterans were younger, unmarried, college graduates, had less combat exposure, but were more likely to have lifetime PTSD (29% vs. 12%.), depression (46% vs. 21%), suicidal ideation (27% vs. 11%), and lifetime mental health service use (67% vs. 47%). Females were also more likely to have low psychological resilience and to have used psychotropic medicines in the past year. Using multivariate logistic regression analyses that controlled for risk and protective factors, female veterans had greater risk for lifetime PTSD, depression, suicidal thoughts, and for lifetime use of psychological services, compared to males. Since 95% of the population in this study were male and these results may have been statistically biased, we reran our analyses using propensity score matching. Results were consistent across these analyses. Conclusion : Using a sample of post-deployment veterans receiving healthcare services from a large non-VA health system, we find that female veterans are at greater risk for lifetime psychological problems, compared to male veterans. We discuss these findings and their implications for service providers.
Charcot–Marie–Tooth disease is a genetically heterogeneous group of motor and sensory neuropathies associated with mutations in more than 30 genes. Charcot–Marie–Tooth disease type 4J (OMIM 611228) is a recessive, potentially severe form of the disease caused by mutations of the lipid phosphatase FIG4. We provide a more complete view of the features of this disorder by describing 11 previously unreported patients with Charcot–Marie–Tooth disease type 4J. Three patients were identified from a small cohort selected for screening because of their early onset disease and progressive proximal as well as distal weakness. Eight patients were identified by large-scale exon sequencing of an unselected group of 4000 patients with Charcot–Marie–Tooth disease. In addition, 34 new FIG4 variants were detected. Ten of the new CMT4J cases have the compound heterozygous genotype FIG4I41T/null described in the original four families, while one has the novel genotype FIG4L17P/null. The population frequency of the I41T allele was found to be 0.001 by genotyping 5769 Northern European controls. Thirty four new variants of FIG4 were identified. The severity of Charcot–Marie–Tooth disease type 4J ranges from mild clinical signs to severe disability requiring the use of a wheelchair. Both mild and severe forms have been seen in patients with the same genotype. The results demonstrate that Charcot–Marie–Tooth disease type 4J is characterized by highly variable onset and severity, proximal as well as distal and asymmetric muscle weakness, electromyography demonstrating denervation in proximal and distal muscles, and frequent progression to severe amyotrophy. FIG4 mutations should be considered in Charcot–Marie–Tooth patients with these characteristics, especially if found in combination with sporadic or recessive inheritance, childhood onset and a phase of rapid progression.
On October 29, 2012, Hurricane Sandy made landfall in the most densely populated region in the US. In New Jersey, thousands of families were made homeless and entire communities were destroyed in the worst disaster in the history of the state. The economic impact of Sandy was huge, comparable to Hurricane Katrina. The areas that sustained the most damage were the small- to medium-sized beach communities along New Jersey's Atlantic coastline. Six months following the hurricane, we conducted a random telephone survey of 200 adults residing in 18 beach communities located in Monmouth County. We found that 14.5% (95% CI = 9.9-20.2) of these residents screened positive for PTSD and 6.0% (95% CI = 3.1-10.2) met criteria for major depression. Altogether 13.5% (95% CI = 9.1-19.0) received mental health counseling and 20.5% (95% CI = 15.1-26.8) sought some type of mental health support in person or online, rates similar to those reported in New York after the World Trade Center disaster In multivariate analyses, the best predictors of mental health status and service use were having high hurricane exposure levels, having physical health limitations, and having environmental health concerns. Research is needed to assess the mental health status and service use of Jersey Shore residents over time, to evaluate environmental health concerns, and to better understand the storm's impact among those with physical health limitations.
Rodent models are important research tools for studying the pathophysiology of traumatic brain injury (TBI) and developing new therapeutic interventions for this devastating neurological disorder. However, the failure rate for the translation of drugs from animal testing to human treatments for TBI is 100%. While there are several potential explanations for this, previous clinical trials have relied on extrapolation from preclinical studies for critical design considerations, including drug dose optimization, post-injury drug treatment initiation and duration. Incorporating clinically relevant biomarkers in preclinical studies may provide an opportunity to calibrate preclinical models to identical (or similar) measurements in humans, link to human TBI biomechanics and pathophysiology, and guide therapeutic decisions. To support this translational goal, we conducted a systematic literature review of preclinical TBI studies in rodents measuring blood levels of clinically used GFAP, UCH-L1, NfL, t-Tau, or p-Tau, published in PubMed/EMBASE up to April 10th, 2024. Although many factors influence clinical TBI outcomes, many of those cannot routinely be assessed in rodent studies (e.g., ICP monitoring), thus we focused on blood biomarkers' temporal trajectories and discuss our findings in the context of the latest clinical TBI biomarker data. Out of the 805 original preclinical studies, 74 met the inclusion criteria, with a median quality score of 5 (25th-75th percentiles: 4-7) on the CAMARADES checklist. GFAP was measured in 43 studies, UCH-L1 in 21, NfL in 20, t-Tau in 19, and p-Tau in seven. Data in rodent models indicate that all biomarkers exhibited injury severity-dependent elevations with distinct temporal profiles. GFAP and UCH-L1 peaked within the first day after TBI (30- and 4-fold increases, respectively, in moderate-to-severe TBI versus sham) with the highest levels observed in the contusion TBI model. NfL peaked within days (18-fold increase) and remained elevated up to 6 months post-injury. GFAP and NfL show a pharmacodynamic response in 64.7% and 60%, respectively, of studies evaluating neuroprotective therapies in preclinical models. However, GFAP's rapid decline post-injury may limit its utility for understanding the response to new therapeutics beyond the hyperacute phase after experimental TBI. Furthermore, as in humans, subacute NfL levels inform on chronic white matter loss after TBI. t-Tau and p-Tau levels increased over weeks after TBI (up to 6- and 16-fold, respectively); however, their relationship with underlying neurodegeneration has yet to be addressed. Further investigation into biomarker levels in the subacute and chronic phases after TBI will be needed to fully understand the pathomechanisms underpinning blood biomarkers' trajectories and select the most suitable experimental model to optimally relate preclinical mechanistic studies to clinical observations in humans. This new approach could accelerate the translation of neuroprotective treatments from laboratory experiments to real-world clinical practices.
Since veteran suicide is a concern and our knowledge of predictive factors is still limited, our objective was to assess risk factors for suicide, including genetic factors, among deployed veterans.For this study, we surveyed 1730 veterans who were outpatients in a multi-hospital system in Pennsylvania. Altogether, 1041 veterans (60%) provided a DNA sample. The genetic risk variants investigated were within loci previously associated with PTSD and substance misuse, including CRHR1, CHRNA5, RORA, and FKBP5 genetic variations, which were used to calculate a polygenic risk score (range=0-8, mean=3.6, SD=1.4).Most veterans (56.2%) were deployed to Vietnam while significant numbers were deployed to Iraq, Afghanistan, and other post-Vietnam conflicts. Overall, 95.1% of the veterans were male, their mean age was 56.2 (SD=12), and 95.6% were Caucasian. Among the veterans, 24% had high combat exposure. The prevalence of lifetime suicidal thoughts was 11.3%. Additionally, 5.7% ever developed a suicide plan or attempted suicide in their lifetimes. Among those with a history of a lifetime suicide attempt or suicide plan, the PTSD genetic risk score was significantly higher (OR=3.96 vs 3.55, p=0.033), but for suicidal thoughts, this association was not significant (p=0.717). In multivariable analysis (MVA) logistic regression, significant predictors of attempting suicide or having a suicide plan were history of depression (OR=5.04, p<0.001), PTSD genetic risk score (OR=1.25, p=0.036), history of childhood abuse/neglect (OR=2.24, p=0.009), and lifetime marijuana use (OR= 1.56, p=0.020). Conversely, rural residence was protective for suicide risk (OR=0.49; p=0.031). For suicidal thoughts, in the MVA genetic risk score was not significant (p=0.697), but history of child abuse/neglect (p<0.001), history of depression (p>0.001), low psychological resilience (p=0.004), and lifetime marijuana use (p=0.022) were significant.In this study, we identified genetic risk variants and other predictors for suicide among veterans that may have implications for future screening and clinical care. Further research is advised.
Abstract Background : This study focuses on factors that may affect female veterans’ mental health, compared to men, and is part of a large study assessing the prevalence of mental health disorders and treatment seeking among formerly deployed US military service members. Methods : We surveyed a random sample of 1,730 veterans who were patients in a large non-VA hospital system in the US. Based on previous research, women were hypothesized to be at higher risk for psychological problems. We adjusted our models for confounding factors, including history of childhood abuse, combat exposure, stressful life events, alcohol misuse, psychological resources, and social support. Results : Among the veterans studied, 5% (N=85) were female, 96% were White, 22.9% were Iraq/Afghanistan veterans, and the mean age was 59 years old. Compared to males, female veterans were younger, unmarried, college graduates, have less combat exposure, but more likely to have lifetime PTSD (29% vs. 12%.), lifetime depression (46% vs. 21%), lifetime suicide ideation (27% vs. 11%), to have ever used psychological services (67 vs. 47%). Females were more likely to have low psychological resilience and use psychotropic medicines. Using multivariate logistic regression analyses that controlled for risk and protective factors, female veterans had greater risk for lifetime PTSD, lifetime depression, and lifetime suicidal thoughts, compared to males. Since 95% of the population in this study were male and these results may have been statistically biased, we reran our analyses using propensity score matching. The results were consistent. Conclusion : Using a sample of post-deployment veterans receiving services from a non-VA healthcare system, we find that female veterans are at greater risk for lifetime psychological problems, compared to male veterans. We discuss these findings and their implications for service providers.
ABSTRACT BACKGROUND AND PURPOSE While sensitive to internal carotid artery (ICA) occlusion, carotid ultrasound can produce false‐positive results. CT angiography (CTA) has a high specificity for ICA occlusion and is safer and cheaper than catheter angiography, although less accurate. We determined the cost‐effectiveness of CTA versus catheter angiography for confirming an ICA occlusion first suggested by carotid ultrasound. METHODS A Markov decision‐analytic model was constructed to estimate the cost‐effectiveness of CTA compared with catheter angiography in a hypothetical cohort of symptomatic patients with a screening examination consistent with an ICA occlusion. Costs in 2004 dollars were estimated from Medicare reimbursement. Effectiveness was measured in quality‐adjusted life years. RESULTS The 2‐year cost in the CTA scenario was $9,178, and for catheter angiography, $11,531, consistent with a $2,353 cost‐savings per person for CTA. CTA resulted in accrual of 1.83 quality‐adjusted life years while catheter angiography resulted in 1.82 quality‐adjusted life years. CTA was less costly and marginally more effective than catheter angiography. In sensitivity analyses, when CTA sensitivity and specificity were allowed to vary across a plausible range, CTA remained cost‐effective. CONCLUSIONS After screening examination has suggested an ICA occlusion, confirmatory testing with CTA provides similar effectiveness to catheter angiography and is less costly.
Several lines of evidence have suggested that decreases in postsynaptic inhibition may have a role in epileptogenesis in cortical structures. However, other studies have suggested that GABAergic inhibition is spared, or even augmented in some forms of post-lesional epilepsy. In the studies described here, inhibitory events were recorded in two models of post-lesional chronic epileptogenesis. (i) As previously reported (D.A. Prince and G.-F. Tseng. J. Neurophysiol. 69: 1276-1291. 1993), epileptiform activity develops in slices from partially isolated rat neocortical islands 2-3 weeks after the initial in vivo lesion. In this model of post-traumatic epilepsy, large amplitude polyphasic inhibitory postsynaptic currents (IPSCs) in layer V pyramidal neurons are associated with each interictal epileptiform field potential. The frequency of spontaneous IPSCs as well as miniature IPSCs was significantly increased in neocortical slices from the epileptogenic chronically injured cortex versus controls. Immunocytochemical reactions for parvalbumin and calbindin, calcium binding proteins present in subgroups of GABAergic neurons, showed an increased staining of both neuropil and somata within the epileptogenic tissue. Immunoreactivity for glutamic acid decarboxylase (GAD) and GABA also appeared to be increased in the neuropil. (ii) Cortical microgyri resembling human malformations were produced by freeze lesions made transcranially in P0 rat cortex (K.M. Jacobs, M.J. Gutnick, and D.A. Prince. Cereb. Cortex, 6: 514-523. 1996). The boundary between the four-layered microgyrus and surrounding cortex become epileptogenic within about 2 weeks, as judged by evoked extracellular field potentials and cellular activities. Epileptogenesis in the surrounding cortex is not altered when the microgyrus itself is isolated by transcortical cuts. Patch-clamp recordings from layer V neurons in the epileptogenic zone showed that spontaneous IPSCs are larger and more dependent on glutamatergic synapses than in control neurons. The amplitudes of polysynaptic IPSCs evoked by threshold stimulation were also larger than in control cells. Although evaluation of inhibitory events in these models is still incomplete, results to date suggest that GABAergic inhibition may be enhanced in epileptogenic areas associated with chronic cortical injury. Sprouting of axonal arborizations of pyramidal cells onto interneurons, upregulation of GABAergic neurons, and perhaps sprouting of inhibitory axons that make increased numbers of contacts onto pyramidal cells may all contribute to the increased inhibitory drive. Results in these models do not support the disinhibitory hypothesis of chronic epileptogenesis.
Neurocognitive disorders commonly occur following cardiac surgery. However, the underlying etiology of these disorders is not well understood. The current study examined the association between perioperative glucose levels and other risk factors and the onset of neurocognitive disorders in adult patients following coronary artery bypass and/or valvular surgery.Adult patients who underwent their first cardiac surgery at a large tertiary care medical center were identified and those with neurocognitive disorders prior to surgery were excluded. Demographic, perioperative, and postoperative neurocognitive outcome data were extracted from the Society for Thoracic Surgery database, and from electronic medical records, between January 2004 and June 2009. Multiple clinical risk factors and measures associated with insulin resistance, such as hyperglycemia, were assessed. Multivariable Cox competing risk survival models were used to assess hyperglycemia and postoperative neurocognitive disorders at follow up, adjusting for other risk factors and confounding variables.Of the 855 patients included in the study, 271 (31.7%) had new onset neurocognitive disorders at follow-up. Age, sex, New York Heart Failure (NYHF) Class, length of postoperative intensive care unit stay, perioperative blood product transfusion, and other key factors were identified and assessed as potential risk factors (or confounders) for neurocognitive disorders at follow-up. Bivariate analyses suggested that new onset neurocognitive disorders were associated with NYHF Class, cardiopulmonary bypass, history of diabetes, intraoperative blood product use, and number of diseased coronary vessels, which are commonly-accepted risk factors in cardiac surgery. In addition, higher first glucose level (median =116 mg/dL) and higher peak glucose >169 mg/dL were identified as risk factors. Male sex and nonuse of intra-operative blood products appeared to be protective. Controlling for potential risk factors and confounders, multivariable Cox survival models suggested that increased perioperative first glucose measured in 20 unit increments, was significantly associated with the onset of postoperative neurocognitive disorders at follow-up (hazard ratio [HR] =1.16, P<0.001) and that women had an elevated risk for this outcome (HR =4.18, P=0.01).Our study suggests that perioperative hyperglycemia was associated with new onset of postoperative neurocognitive disorders in adult patients after cardiac surgery, and that men tended to be protected from these outcomes. These findings may suggest a need for the revision of clinical protocols for perioperative insulin therapy to prevent long-term neurocognitive complications.
