Fear of progression in chronic illnesses other than cancer: a systematic review and meta-analysis of a transdiagnostic construct.

Fear of cancer recurrence (FCR) is the most common psychosocial issue amongst cancer survivors. However, fear of progression (FoP) has rarely been studied outside of the cancer context. This review aimed to: (1) meta-synthesise qualitative studies of FoP in illnesses other than cancer; and (2) quantify the relationship between FoP and anxiety, depression, and quality of life (QoL) in non-cancer chronic illnesses. We identified 25 qualitative and 11 quantitative studies in a range of chronic illnesses. Participants described fears of progression and recurrence of their illness, including fears of dying, and fears of becoming a burden to family. Fears were often triggered by downward comparison (i.e., seeing people worse off than themselves). Participants coped in different ways, including by accepting the illness or seeking knowledge. Those for whom these fears caused distress reported hypervigilance to physical symptoms and avoidance. Distress, and seeking information, were associated with adherence. In quantitative analyses, FoP was moderately associated with QoL, and strongly associated with anxiety and depression. These results suggest that FoP in illnesses other than cancer is similar to FCR. FoP appears to be an important transdiagnostic construct associated with distress. Evidence-based FCR interventions could be adapted to better manage FoP in other illnesses.

The upper limb of Paranthropus boisei from Ileret, Kenya.

Paranthropus boisei was first described in 1959 based on fossils from the Olduvai Gorge and now includes many fossils from Ethiopia to Malawi. Knowledge about its postcranial anatomy has remained elusive because, until recently, no postcranial remains could be reliably attributed to this taxon. Here, we report the first associated hand and upper limb skeleton (KNM-ER 47000) of P. boisei from 1.51 to 1.53 Ma sediments at Ileret, Kenya. While the fossils show a combination of primitive and derived traits, the overall anatomy is characterized by primitive traits that resemble those found in Australopithecus, including an oblique scapular spine, relatively long and curved ulna, lack of third metacarpal styloid process, gracile thumb metacarpal, and curved manual phalanges. Very thick cortical bone throughout the upper limb shows that P. boisei had great upper limb strength, supporting hypotheses that this species spent time climbing trees, although probably to a lesser extent than earlier australopiths. Hand anatomy shows that P. boisei, like earlier australopiths, was capable of the manual dexterity needed to create and use stone tools, but lacked the robust thumb of Homo erectus, which arguably reflects adaptations to the intensification of precision grips and tool use. KNM-ER 47000 provides conclusive evidence that early Pleistocene hominins diverged in postcranial and craniodental anatomy, supporting hypotheses of competitive displacement among these contemporaneous hominins.

Fasting salivary glucose levels is not a better measure for identifying diabetes mellitus than serum or capillary blood glucose levels: comparison in a Ghanaian population.

AIMS/INTRODUCTION: We compared the diagnostic performance and correlation between salivary, serum and capillary blood glucose of diabetes and non-diabetes patients. Early detection of diabetes mellitus (DM) contributes to the prevention of complications and management. MATERIALS AND METHODS: This case-control study was conducted among a total of 138 participants comprising 79 newly diagnosed diabetes patients (cases) and 59 non-diabetes patients (controls). Fasting salivary glucose (FSLG), fasting serum glucose (FSEG) levels and fasting capillary whole blood glucose (FCWBG) level were assayed for each participant. RESULTS: The mean FSLG, FSEG and FCWBG levels were significantly higher among the cases compared to controls (p < 0.0001). There was a significant mean difference between the levels of FSLG vs. FSEG (p < 0.0001) and FSLG vs. FCWBG (p < 0.0001) but not levels of FSEG vs. FCWBG (p > 0.05) in both cases and controls. A positive correlation was observed between FSLG and FSEG (r = 0.89; p < 0.0001) and FCWBG (r = 0.87; p < 0.0001). At the cut-off value >6.8 mmol/l for FSEG, a sensitivity of 99%, specificity of 100.0% and area under the curve (AUC) of 98.8% was observed for predicting DM while a sensitivity of 80%, specificity of 95% and AUC of 91.0% was observed for FSLG at a cut-off value >0.5 mmol/l. At the cut-off value >6.9 mmol/l for FCWBG, a sensitivity of 100.0%, specificity of 100.0% and AUC of 100.0% was observed for predicting DM. CONCLUSION: Fasting salivary glucose (FSLG) levels increased with increasing blood glucose levels. However, it does not generate enough diagnostic and predictive accuracy compared to capillary whole blood glucose which less invasive.

Genetic polymorphisms in NAT1, NAT2, GSTM1, GSTP1 and GSTT1 and susceptibility to colorectal cancer among Filipinos

@#Objectives. Polymorphisms in metabolic genes which alter rates of bioactivation and detoxification have been shown to modulate susceptibility to colorectal cancer. This study sought to evaluate the colorectal cancer risk from environmental factors and to do polymorphism studies on genes that code for Phase I and II xenobiotic metabolic enzymes among Filipino colorectal cancer patients and matched controls. Methods. A total of 224 colorectal cancer cases and 276 controls from the Filipino population were genotyped for selected polymorphisms in GSTM1, GSTP1, GSTT1, NAT1 and NAT2. Medical and diet histories, occupational exposure and demographic data were also collected for all subject participants.Results. Univariate logistic regression of non-genetic factors identified exposure to UV (sunlight) (OR 1.99, 95% CI: 1.16-3.39) and wood dust (OR 2.66, 95% CI: 1.21-5.83) and moldy food exposure (OR 1.61, 95% CI:1.11-2.35) as risk factors; while the NAT2*6B allele (recessive model OR 1.51, 95% CI :1.06-2.16; dominant model OR 1.87, 95% CI: 1.05-3.33) and homozygous genotype (OR 2.19, 95% CI: 1.19-4.03) were found to be significant among the genetic factors. After multivariate logistic regression of both environmental and genetic factors, only UV radiation exposure (OR 2.08, 95% CI: 1.21-3.58) and wood dust exposure (OR 2.08, 95% CI: 0.95-5.30) remained to be significantly associated with increasing colorectal cancer risk in the study population.Conclusion. This study demonstrated that UV sunlight and wood dust exposure play a greater role in influencing colorectal cancer susceptibility than genotype status from genetic polymorphisms of the GST and the NAT` genes.

The prevalence of CYP2D6 Gene Polymorphisms among Filipinos and their use as biomarkers for lung cancer risk

Objectives@#The highly polymorphic nature of the CYP2D6 gene and its central role in the metabolism of commonly used drugs make it an ideal candidate for pharmacogenetic screening. This study aims to determine the prevalence of CYP2D6 polymorphisms among Filipinos and their association to lung cancer. @*Method@#Forty seven single nucleotide polymorphisms (SNPs) of the CYP2D6 gene were genotyped from DNA samples of 115 cases with lung cancer and age- and sex-matched 115 controls. @*Results@#Results show that 18 out of 47 polymorphisms have significant genotypic variability (>1% for at least 2 genotypes). No variant is associated with lung cancer. However, rs1135840, rs16947 and rs28360521, were found to be highly variable among Filipinos. @*Conclusion@#This study demonstrated that CYP2D6 polymorphisms are present among Filipinos, which, although not found to be associated with lung cancer, can be useful biomarkers for future pharmacogenetic studies. The SNP rs16947 is found to be associated with cancer and timolol-induced bradycardia; the SNP rs1135840, on the other hand, is only shown to be linked with cancer. The genetic variant rs28360521 is known to be associated with low-dose aspirin-induced lower gastrointestinal bleeding.

Biomechanical strategies for accuracy and force generation during stone tool production.

Multiple hominin species used and produced stone tools, and the archaeological record provides evidence that stone tool behaviors intensified among later members of the genus Homo. This intensification is widely thought to be the product of cognitive and anatomical adaptations that enabled later Homo taxa to produce stone tools more efficiently relative to earlier hominin species. This study builds upon recent investigations of the knapping motions of modern humans to test whether aspects of our upper limb anatomy contribute to accuracy and/or efficiency. Knapping kinematics were captured from eight experienced knappers using a Vicon motion capture system. Each subject produced a series of Oldowan bifacial choppers under two conditions: with normal wrist mobility and while wearing a brace that reduced wrist extension (∼30°-35°), simulating one aspect of the likely primitive hominin condition. Under normal conditions, subjects employed a variant of the proximal-to-distal joint sequence common to throwing activities: subjects initiated down-swing upper limb motion at the shoulder and proceeded distally, increasing peak linear and angular velocities from the shoulder to the elbow to the wrist. At the wrist, subjects utilized the 'dart-thrower's arc,' the most stable plane of radiocarpal motion, during which wrist extension is coupled with radial deviation and flexion with ulnar deviation. With an unrestrained wrist, subjects achieved significantly greater target accuracy, wrist angular velocities, and hand linear velocities compared with the braced condition. Additionally, the modern wrist's ability to reach high degrees of extension (≥28.5°) following strike may decrease risk of carpal and ligamentous damage caused by hyperextension. These results suggest that wrist extension in humans contributes significantly to stone tool-making performance.

Injection parameters and virus dependent choice of promoters to improve neuron targeting in the nonhuman primate brain.

We, like many others, wish to use modern molecular methods to alter neuronal functionality in primates. For us, this requires expression in a large proportion of the targeted cell population. Long generation times make germline modification of limited use. The size and intricate primate brain anatomy poses additional challenges. We surved methods using lentiviruses and serotypes of adeno-associated viruses (AAVs) to introduce active molecular material into cortical and subcortical regions of old-world monkey brains. Slow injections of AAV2 give well-defined expression of neurons in the cortex surrounding the injection site. Somewhat surprisingly we find that in the monkey the use of cytomegalovirus promoter in lentivirus primarily targets glial cells but few neurons. In contrast, with a synapsin promoter fragment the lentivirus expression is neuron specific at high transduction levels in all cortical layers. We also achieve specific targeting of tyrosine hydroxlase (TH)- rich neurons in the locus coeruleus and substantia nigra with a lentvirus carrying a fragment of the TH promoter. Lentiviruses carrying neuron specific promoters are suitable for both cortical and subcortical injections even when injected quickly.

Effects of broad-spectrum antimycobacterial therapy on chronic pulmonary sarcoidosis.

BACKGROUND: Sarcoidosis is an idiopathic, granulomatous disease for which molecular and immunologic studies have shown an association between it and mycobacterial antigens. Microbial antigens can reduce expression of the tyrosine kinase Lck, which has been associated with sarcoidosis severity. Here we investigate the efficacy of Concomitant Levofloxacin, Ethambutol, Azithromycin, and Rifampin (the CLEAR regimen) for treatment of chronic, pulmonary sarcoidosis. METHODS: Fifteen chronic, pulmonary sarcoidosis patients with forced vital capacities (FVC) between 45-80% of predicted were enrolled in this open-label trial. The primary efficacy endpoint was change in absolute FVC from baseline to completion of therapy. Secondary endpoints were change in functional capacity measured by Six Minute Walk Distance (6MWD) and quality of life assessment measured by St. George's Respiratory Questionnaire (SGRQ). RESULTS: Of 15 patients enrolled, 11 completed 4 weeks of therapy, and 8 completed 8 weeks of therapy. The CLEAR regimen was associated with an increase in FVC of 0.23 liters at 4 weeks and 0.42 liters at 8 weeks (P=0.0098 and 0.016, respectively). The 6MWD increased by 87 meters from baseline to 8 weeks (p=0.0078). The mean score of the validated SGRQ was improved at 8 weeks over baseline (p=0.023). Normalized expression of Lck and NF-κB was observed in those with clinical improvement. CONCLUSIONS: The CLEAR regimen is associated with improved absolute FVC, as well as increased functional capacity and quality-of-life in selected chronic pulmonary sarcoidosis patients. Larger, randomized, controlled trials are needed to confirm these findings and to identify patients most likely to benefit from therapy. ClinicalTrials.gov number NCT01169038.

Upper limb kinematics and the role of the wrist during stone tool production.

Past studies have hypothesized that aspects of hominin upper limb morphology are linked to the ability to produce stone tools. However, we lack the data on upper limb motions needed to evaluate the biomechanical context of stone tool production. This study seeks to better understand the biomechanics of stone tool-making by investigating upper limb joint kinematics, focusing on the role of the wrist joint, during simple flake production. We test the hypotheses, based on studies of other upper limb activities (e.g., throwing), that upper limb movements will occur in a proximal-to-distal sequence, culminating in rapid wrist flexion just prior to strike. Data were captured from four amateur knappers during simple flake production using a VICON motion analysis system (50 Hz). Results show that subjects utilized a proximal-to-distal joint sequence and disassociated the shoulder joint from the elbow and wrist joints, suggesting a shared strategy employed in other contexts (e.g., throwing) to increase target accuracy. The knapping strategy included moving the wrist into peak extension (subject peak grand mean = 47.3 degrees) at the beginning of the downswing phase, which facilitated rapid wrist flexion and accelerated the hammerstone toward the nodule. This sequence resulted in the production of significantly more mechanical work, and therefore greater strike forces, than would otherwise be produced. Together these results represent a strategy for increasing knapping efficiency in Homo sapiens and point to aspects of skeletal anatomy that might be examined to assess potential knapping ability and efficiency in fossil hominin taxa.

Cross-sectional geometric analysis of a foot bone assemblage from Mangaia, Cook Islands.

This study describes a human foot bone assemblage from prehistoric Mangaia, Cook Islands in the context of diaphyseal cross-sectional strength measures. We use this sample to test the hypothesis that habitually unshod individuals who walk over rugged terrain will have stronger foot bones than a sample of habitually shod industrialized people. Specifically, we examine whether the Mangaian sample has a stronger size-adjusted metatarsal (MT) and phalangeal cross-sectional properties than the industrial sample, drawn from the Terry Collection. Contrary to expectations, residual analyses showed that most values of cross-sectional area (CA) and torsional resistance (J) of MTs 1-4 and the hallucal proximal phalanx (HPP) of the Mangaians are among those in the lower range of the Terry Collection sample. However, the bending strength ratios (Zy/Zx) of the Mangaian HPP are significantly greater than those of the Terry Collection. While characteristics such as forefoot shape variation between the sexes and among geographic populations cannot be ruled out as influential factors, cross-sectional properties of the hallucal proximal phalanges, but not the MTs, indicate terrain complexity in prehistoric populations.

Comment on "Origin of human bipedalism as an adaptation for locomotion on flexible branches".

Thorpe et al. (Reports, 1 June 2007, p. 1328) concluded that human bipedalism evolved from a type of bipedal posture they observed in extant orangutans with seemingly human-like extended knees. However, humans share knuckle-walking characters with African apes that are absent in orangutans. These are most parsimoniously explained by positing a knuckle-walking precursor to human bipedalism.

Excess synchrony in motor cortical neurons provides redundant direction information with that from coarse temporal measures.

Previous studies have shown that measures of fine temporal correlation, such as synchronous spikes, across responses of motor cortical neurons carries more directional information than that predicted from statistically independent neurons. It is also known, however, that the coarse temporal measures of responses, such as spike count, are not independent. We therefore examined whether the information carried by coincident firing was related to that of coarsely defined spike counts and their correlation. Synchronous spikes were counted in the responses from 94 pairs of simultaneously recorded neurons in primary motor cortex (MI) while monkeys performed arm movement tasks. Direct measurement of the movement-related information indicated that the coincident spikes (1- to 5-ms precision) carry approximately 10% of the information carried by a code of the two spike counts. Inclusion of the numbers of synchronous spikes did not add information to that available from the spike counts and their coarse temporal correlation. To assess the significance of the numbers of coincident spikes, we extended the stochastic spike count matched (SCM) model to include correlations between spike counts of the individual neural responses and slow temporal dependencies within neural responses (approximately 30 Hz bandwidth). The extended SCM model underestimated the numbers of synchronous spikes. Therefore as with previous studies, we found that there were more synchronous spikes in the neural data than could be accounted for by this stochastic model. However, the SCM model accounts for most (R(2) = 0.93 +/- 0.05, mean +/- SE) of the differences in the observed number of synchronous spikes to different directions of arm movement, indicating that synchronous spiking is directly related to spike counts and their broad correlation. Further, this model supports the information theoretic analysis that the synchronous spikes do not provide directional information beyond that available from the firing rates of the same pool of directionally tuned MI neurons. These results show that detection of precisely timed spike patterns above chance levels does not imply that those spike patterns carry information unavailable from coarser population codes but leaves open the possibility that excess synchrony carries other forms of information or serves other roles in cortical information processing not studied here.

Consistency of encoding in monkey visual cortex.

Are different kinds of stimuli (for example, different classes of geometric images or naturalistic images) encoded differently by visual cortex, or are the principles of encoding the same for all stimuli? We examine two response properties: (1) the range of spike counts that can be elicited from a neuron in epochs representative of short periods of fixation (up to 400 msec), and (2) the relation between mean and variance of spike counts elicited by different stimuli, that together characterize the information processing capabilities of a neuron using the spike count code. In monkey primary visual cortex (V1) complex cells, we examine responses elicited by static stimuli of four kinds (photographic images, bars, gratings, and Walsh patterns); in area TE of inferior temporal cortex, we examine responses elicited by static stimuli in the sample, nonmatch, and match phases of a delayed match-to-sample task. In each area, the ranges of mean spike counts and the relation between mean and variance of spike counts elicited are sufficiently similar across experimental conditions that information transmission is unaffected by the differences across stimulus set or behavioral conditions [although in 10 of 27 (37%) of the V1 neurons there are statistically significant but small differences, the median difference in transmitted information for these neurons was 0.9%]. Encoding therefore appears to be consistent across experimental conditions for neurons in both V1 and TE, and downstream neurons could decode all incoming signals using a single set of rules.

Image distribution in a multi-facility radiology practice.

The Cleveland Clinic Health System is a multifacility practice that distributes images electronically. Issues specific to the internal department at the main campus must be addressed with regard to the overall commitment to the healthcare system. Training for new and old employees on diagnostic and transcription equipment is a key issue. Interfacing different systems or different configurations of a system, either hospital or radiology information systems, is many times difficult and sometimes insurmountable. Issues of confidentiality have been addressed. In light of the impending new regulations from the Health Insurance Portability and Accountability Act, are the current system security practices enough?

Suicide trends in Wisconsin 1984-1998: good news for young and old.

PROBLEM: In Wisconsin, suicide is the eighth leading cause of death. Subgroups identified as being at higher risk are the elderly (> age 65) and young adults (aged 15-24). OBJECTIVES: 1) To compare overall national trends in suicide rates to Wisconsin trends in suicide rates from 1984 to 1998; 2) to examine suicide rates in Wisconsin sub-groups (age, gender and race) 1984-1998; and 3) to assess progress toward Wisconsin's Public Health Agenda for the Year 2000 suicide mortality goals. METHODS: National Center for Injury Control and Prevention data on suicide mortality were accessed for the United States and Wisconsin using WISQARS data extraction system. Mean suicide rates were calculated for two 5-year spans (1984-1988 and 1994-1998). Average numbers of deaths and percent change between mortality rates were calculated for the two 5-year spans. RESULTS: From 1984-1998, mean suicide mortality rates decreased 8% nationally and 14% in Wisconsin. Various trends are occurring between genders and ages. The current declines in teens 15-19 and elderly 75-84 may indicate reversals of previous trends. Rates for women decreased for nearly all age groups, continuing previously documented declines. While it appears progress has been made toward Wisconsin Public Health Agenda goals, it appears unlikely the overall objective of 8 per 100,000 will be met.

Testing the taxonomic integrity of Paranthropus boisei sensu stricto.

The craniodental hypodigm of Paranthropus boisei sensu stricto is morphologically distinctive, but it has been suggested that the substantial variation in mandibular and dental size in that hypodigm may exceed that which is reasonable to subsume within a single hominin species. In this study, Fligner and Killeen, coefficient of variation (CV)-based and average taxonomic distance (ATD)-based bootstrap tests, were used to compare variation in size and shape of the mandibular corpus remains attributed to P. boisei s.s. with the variation observed in samples of great apes and modern humans. The degree of size variation in the P. boisei s.s. mandibular hypodigm is never observed in human and chimpanzee samples, is rare in gorillas, but is not uncommon in orangutans. However, the shape variation in the fossil group is comparable to the variation in the extant reference groups. Although the size variation in P. boisei s.s. is substantial, it is exaggerated by the effects of taphonomy. The small mandibles are more often abraded, whereas the large mandibles are more likely to have been infiltrated with matrix. On the basis of the results of this investigation of the mandibular corpus, there are no grounds for rejecting the "single-species" hypothesis for P. boisei s.s. When Sokal and Braumann's adjusted CV values were used to predict the index of sexual dimorphism (ISD) for the P. boisei s.s., despite the substantial geological time embraced by the mandibular corpus hypodigm, the predicted value of lnISD, when corrected for taphonomic factors, is comparable to the sexual dimorphism observed within Gorilla.

Unusual facet cyst containing struvite and hydroxyapatite.

This case report describes a patient with severe back pain and radiculopathy. She was found to have a facet cyst within the lumbar spine that appeared to contain calcium on MRI and CT. Upon aspiration the cyst was found to contain calcium ammonium phosphate (struvite) and calcium phosphate (hydroxyapatite). Ammonia production in the presence of urease-producing bacteria is responsible for the production of struvite in the human body. We postulate that there was a prior infection of the facet with urease-producing bacteria, thus accounting for the production of the struvite within the facet cyst.

Role of perirhinal cortex in object perception, memory, and associations.

The perirhinal cortex plays a key role in acquiring knowledge about objects. It contributes to at least four cognitive functions, and recent findings provide new insights into how the perirhinal cortex contributes to each: first, it contributes to recognition memory in an automatic fashion; second, it probably contributes to perception as well as memory; third, it helps identify objects by associating together the different sensory features of an object; and fourth, it associates objects with other objects and with abstractions.