Distinct networks of periaqueductal gray columns in pain and threat processing.

Noxious events that can cause physical damage to the body are perceived as threats. In the brainstem, the periaqueductal gray (PAG) ensures survival by generating an appropriate response to these threats. Hence, the experience of pain is coupled with threat signaling and interfaces in the dl/l and vlPAG columns. In this study, we triangulate the functional circuits of the dl/l and vlPAG by using static and time-varying functional connectivity (FC) in multiple fMRI scans in healthy participants (n = 37, 21 female). The dl/l and vlPAG were activated during cue, heat, and rating periods when the cue signaled a high threat of experiencing heat pain and when the incoming intensity of heat pain was unknown. Responses were significantly lower after low threat cues. The two regions responded similarly to the cued conditions but showed prominent distinctions in the extent of FC with other brain regions. Thus, both static and time-varying FC showed significant differences in the functional circuits of dl/l and vlPAG in rest and task scans. The dl/lPAG consistently synchronized with the salience network and the thalamus, suggesting a role in threat detection, while the vlPAG exhibited more widespread synchronization and frequently connected with memory/language and sensory regions. Hence, these two PAG regions process heat pain when stronger pain is expected or when it is uncertain, and preferentially synchronize with distinct brain circuits in a reproducible manner. The dl/lPAG seems more directly involved in salience detection, while the vlPAG seems engaged in contextualizing threats.

Threat Prediction from Schemas as a Source of Bias in Pain Perception.

Our sensory impressions of pain are generally thought to represent the noxious properties of an agent but can be influenced by the predicted level of threat. Predictions can be sourced from higher-order cognitive processes, such as schemas, but the extent to which schemas can influence pain perception relative to bottom-up sensory inputs and the underlying neural underpinnings of such a phenomenon are unclear. Here, we investigate how threat predictions generated from learning a cognitive schema lead to inaccurate sensory impressions of the pain stimulus. Healthy male and female participants first detected a linear association between cue values and stimulus intensity and rated pain to reflect the linear schema when compared with uncued heat stimuli. The effect of bias on pain ratings was reduced when prediction errors (PEs) increased, but pain perception was only partially updated when measured against stepped increases in PEs. Cognitive, striatal, and sensory regions graded their responses to changes in predicted threat despite the PEs (p < 0.05, corrected). Individuals with more catastrophic thinking about pain and with low mindfulness were significantly more reliant on the schema than on the sensory evidence from the pain stimulus. These behavioral differences mapped to variability in responses of the striatum and ventromedial prefrontal cortex. Thus, this study demonstrates a significant role of higher-order schemas in pain perception and indicates that pain perception is biased more toward predictions and less toward nociceptive inputs in individuals who report less mindfulness and more fear of pain.SIGNIFICANCE STATEMENT This study demonstrates that threat predictions generated from cognitive schemas continue to influence pain perception despite increasing prediction errors arising in pain pathways. Individuals first formed a cognitive schema of linearity in the relationship between the cued threat value and the stimulus intensity. Subsequently, the linearity was reduced gradually, and participants partially updated their evaluations of pain in relation to the stepped increases in prediction errors. Individuals who continued to rate pain based more on the predicted threat than on changes in nociceptive inputs reported high pain catastrophizing and less mindful-awareness scores. These two affects mapped to activity in the ventral and dorsal striatum, respectively. These findings direct us to a significant role of top-down processes in pain perception.

Utility of recorded guided imagery and relaxing music in reducing patient pain and anxiety, and surgeon anxiety, during cutaneous surgical procedures: A single-blinded randomized controlled trial.

BACKGROUND: Guided imagery and music can reportedly reduce pain and anxiety during surgery, but no comparative study has been performed for cutaneous surgery to our knowledge. OBJECTIVES: We sought to determine whether short-contact recorded guided imagery or relaxing music could reduce patient pain and anxiety, and surgeon anxiety, during cutaneous surgical procedures. METHODS: Subjects were adults undergoing excisional surgery for basal and squamous cell carcinoma. Randomization was to guided imagery (n = 50), relaxing music (n = 54), or control group (n = 51). Primary outcomes were pain and anxiety measured using visual analog scale and 6-item short-form of the State-Trait Anxiety Inventory, respectively. Secondary outcomes were anxiety of surgeons measured by the 6-item short-form of the State-Trait Anxiety Inventory and physical stress of patients conveyed by vital signs, respectively. RESULTS: There were no significant differences in subjects' pain, anxiety, blood pressure, and pulse rate across groups. In the recorded guided imagery and the relaxing music group, surgeon anxiety was significantly lower than in the control group. LIMITATIONS: Patients could not be blinded. CONCLUSION: Short-contact recorded guided imagery and relaxing music appear not to reduce patient pain and anxiety during excisional procedures under local anesthetic. However, surgeon anxiety may be reduced when patients are listening to such recordings.

Archeological Echocardiography: Digitization and Speckle Tracking Analysis of Archival Echocardiograms in the HyperGEN Study.

BACKGROUND: Several large epidemiologic studies and clinical trials have included echocardiography, but images were stored in analog format and these studies predated tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE). We hypothesized that digitization of analog echocardiograms, with subsequent quantification of cardiac mechanics using STE, is feasible, reproducible, accurate, and produces clinically valid results. METHODS: In the NHLBI HyperGEN study (N = 2234), archived analog echocardiograms were digitized and subsequently analyzed using STE to obtain tissue velocities/strain. Echocardiograms were assigned quality scores and inter-/intra-observer agreement was calculated. Accuracy was evaluated in: (1) a separate second study (N = 50) comparing prospective digital strain versus post hoc analog-to-digital strain, and (2) in a third study (N = 95) comparing prospectively obtained TDI e' velocities with post hoc STE e' velocities. Finally, we replicated previously known associations between tissue velocities/strain, conventional echocardiographic measurements, and clinical data. RESULTS: Of the 2234 HyperGEN echocardiograms, 2150 (96.2%) underwent successful digitization and STE analysis. Inter/intra-observer agreement was high for all STE parameters, especially longitudinal strain (LS). In accuracy studies, LS performed best when comparing post hoc STE to prospective digital STE for strain analysis. STE-derived e' velocities correlated with, but systematically underestimated, TDI e' velocity. Several known associations between clinical variables and cardiac mechanics were replicated in HyperGEN. We also found a novel independent inverse association between fasting glucose and LS (adjusted ß = -2.4 [95% CI -3.6, -1.2]% per 1-SD increase in fasting glucose; P < 0.001). CONCLUSIONS: Archeological echocardiography, the digitization and speckle tracking analysis of archival echocardiograms, is feasible and generates indices of cardiac mechanics similar to contemporary studies.

Myocardial T2-mapping and velocity mapping: changes in regional left ventricular structure and function after heart transplantation.

Monitoring post cardiac transplant (TX) status relies on frequent invasive techniques such as endomyocardial biopsies and right heart cardiac catheterization. The aim of this study was to noninvasively evaluate regional myocardial structure, function, and dyssynchrony in TX patients. Myocardial T2-mapping and myocardial velocity mapping of the left ventricle (basal, midventricular, and apical short-axis locations) was applied in 10 patients after cardiac transplantation (49 ± 13 years, n = 2 with signs of mild rejection, time between TX and MRI = 1-64 months) and compared to healthy controls (n = 20 for myocardial velocity mapping and n = 14 for T2). Segmental analysis based on the 16-segment American Heart Association model revealed increased T2 (P = 0.0003) and significant (P < 0.0001) reductions in systolic and diastolic radial and long-axis peak myocardial velocities in TX patients without signs of rejection compared to controls. Multiple comparisons of individual left ventricular segments demonstrated reductions of long-axis peak velocities in 50% of segments (P < 0.001) while segmental T2 values were not significantly different. Systolic radial as well as diastolic radial and long-axis dyssynchrony were significantly (P < 0.04) increased in TX patients indicating less coordinated contraction, expansion, and lengthening. Correlation analysis revealed moderate but significant (P < 0.010) inverse relationships between myocardial T2 and long-axis peak velocities suggesting a structure-function relationship between altered T2 and myocardial function.

Left atrial flow velocity distribution and flow coherence using four-dimensional FLOW MRI: a pilot study investigating the impact of age and Pre- and Postintervention atrial fibrillation on atrial hemodynamics.

PURPOSE: To use four-dimensional (4D) flow MRI to characterize and quantify 3D blood flow in the left atria (LA) of patients with a history of atrial fibrillation (AF). MATERIALS AND METHODS: The 4D flow MRI was acquired in 19 volunteers (n = 9<30 years, n = 10>50 years) and 10 patients with AF (62 ± 9.6 years; n = 4 in persistent AF, n = 6 postintervention). The LA in each dataset was segmented, and intra-atrial blood flow velocity was quantified. Flow coherence was measured as the consistency of the net blood flow vector. RESULTS: Quantification of atrial flow revealed significant differences in atrial hemodynamics between age groups. Postintervention AF patients had a mean blood flow of 0.22 ± 0.04 m/s, which was not significantly different than age-matched volunteers (0.21 ± 0.03 m/s). Patients with persistent AF had a mean blood flow of 0.13 ± 0.01 m/s, lower than AF patients in sinus rhythm (0.22 ± 0.04 m/s, P = 0.005), or age-matched volunteers (0.21 ± 0.03 m/s, P < 0.001). Flow coherence was significantly impaired in patients in AF. CONCLUSION: Flow-sensitive MRI shows that patients with a history of AF had global hemodynamics in the LA similar to those of age-matched volunteers. Additional studies with larger cohorts of AF patients and correlation with outcome are needed to further investigate the potential of atrial 4D flow MRI to flow patterns indicative of stroke risk in AF.

Population-Level Access to Breast Cancer Early Detection and Diagnosis in Nigeria.

PURPOSE: Mammography, breast ultrasound (US), and US-guided breast biopsy are essential services for breast cancer early detection and diagnosis. This study undertook a comprehensive evaluation to determine population-level access to these services for breast cancer early detection and diagnosis in Nigeria using a previously validated geographic information system (GIS) model. METHODS: A comprehensive list of public and private facilities offering mammography, breast US, and US-guided breast biopsy was compiled using publicly available facility data and a survey administered nationally to Nigerian radiologists. All facilities were geolocated. A cost-distance model using open-source population density (GeoData Institute) and road network data (OpenStreetMap) was used to estimate population-level travel time to the nearest facility for mammography, breast US, and US-guided biopsy using GIS software (ArcMAP). RESULTS: In total, 1,336 facilities in Nigeria provide breast US, of which 47.8% (639 of 1,336) are public facilities, and 218 provide mammography, of which 45.4% (99 of 218) are public facilities. Of the facilities that provide breast US, only 2.5% (33 of 1,336) also provide US-guided breast biopsy. At the national level, 83.1% have access to either US or mammography and 61.7% have access to US-guided breast biopsy within 120 minutes of a continuous one-way travel. There are differences in access to mammography (64.8% v 80.6% with access at 120 minutes) and US-guided breast biopsy (49.0% v 77.1% with access at 120 minutes) between the northern and southern Nigeria and between geopolitical zones. CONCLUSION: To our knowledge, this is the first comprehensive evaluation of breast cancer detection and diagnostic services in Nigeria, which demonstrates geospatial inequalities in access to mammography and US-guided biopsy. Targeted investment is needed to improve access to these essential cancer care services in the northern region and the North East geopolitical zone.

Prosthetic rehabilitation of a patient with an orbital defect: a simplified approach.

Large oro-facial defects consequences in serious functional as well as cosmetic deformities. Acceptable cosmetic results usually can be obtained with a facial prosthesis. This article describes prosthetic rehabilitation of a 35 year-old female having a left orbital defect with HTV silicone material. A modified technique to fabricate an acrylic substructure in heat-polymerizing polymethyl-methacrylate to support silicone facial prosthesis was illustrated. The resultant facial prosthesis was structurally durable and esthetically acceptable with satisfactory retention. This technique is advantageous as there is no need to fabricate the whole prosthesis again in case of damage of the silicone layer because the outer silicone layer can be removed and repacked on the substructure if the gypsum-mold is preserved.

Prosthetic rehabilitation of a patient with finger amputation using silicone material.

AIM: Finger and partial finger amputations are commonly due to traumatic injuries; digit loss may also be attributed to congenital malformations and disease. Finger prostheses are difficult to fabricate as they demand both aesthetic and function. When dealing with these types of prostheses, the only method of gaining successful retention is to sleeve the remnant stump with thin silicone. CASE DESCRIPTION AND METHODS: A 28-year-old man reported with a chief complaint of unaesthetic look due to amputated ring finger of left hand. In this case, the remnant stump was missing, the adjacent ring finger was splinted and an adhesive retained prosthesis instead of ring retained or glove-on prosthesis was planned. The retention was achieved by extending the prosthesis to palmar crease. FINDINGS AND OUTCOME: This article describes the rehabilitation of a finger with prosthesis, which is simple to construct, aesthetic, retentive and easy to maintain. The prosthesis thus fabricated merged with the adjacent tissues providing desired aesthetics and psychological boost to the patient. CONCLUSION: Final prosthesis was found with adequate retention. The patient was satisfied with the aesthetic of the prosthesis. CLINICAL RELEVANCE: Because of the missing residual stump, functional limitations were also there. This clinical report describes a technological process of designing and manufacturing a silicone rubber prosthesis for a patient who has a finger loss caused due to trauma.

Effect of Needle Size on Pain Perception in Patients Treated With Botulinum Toxin Type A Injections: A Randomized Clinical Trial.

IMPORTANCE: Transcutaneous injection through smaller hollow-bore needles may decrease patient discomfort, but current evidence is equivocal. OBJECTIVE: To compare injection discomfort in patients treated with botulinum toxin type A with 30- and 32-gauge needles. DESIGN, SETTING, AND PARTICIPANTS: Split-face, patient- and injector-blinded randomized clinical trial at the dermatology service of an urban university medical center. The 20 participants were women aged 25 to 70 years in good health and with moderate dynamic forehead and glabellar wrinkles. Data were collected from November 20, 2013, through January 16, 2014. Follow-up was complete on January 16, 2014. Data from the per-protocol population were analyzed from July 1 to July 31, 2014. INTERVENTIONS: One side of each patient'sforehead received botulinum toxin type A in saline injected with a 32-gauge needle; the other side received the same treatment injected with a 30-gauge needle. In addition, each patient received randomized injections of saline only to both upper inner arms with the same types of needles. MAIN OUTCOMES AND MEASURES: Primary outcomes included the patient-reported pain rating on a visual analog scale (VAS) on either side of the face and arms and the proportion of patients whose VAS ratings corresponded with more than moderate (ie, clinically significant) pain. The secondary outcome consisted of patient-reported information about the character of the pain at both sites using the expanded and revised version of the Short-Form McGill Pain Questionnaire. RESULTS: All 20 patients completed the study. Overall, facial and arm injections were nominally but not significantly more painful with 30-gauge needles (mean [SD] VAS ratings for the face, 4.16 [2.55] vs 3.41 [2.31], P = .34; for the arm, 1.66 [2.07] vs 1.21 [1.65], P = .45). For facial injections, the likelihood of clinically significant pain (VAS rating, ≥5.4) was significantly greater with 30-gauge needles, which were associated with such pain in 8 patients (40%) compared with the 32-gauge needles, which were associated with such pain in 3 patients (15%) (odds ratio, 3.80 [95% CI, 1.05-13.78]; P = .04). No difference was found in the character of pain associated with needle bore (P > .05 for all comparisons). CONCLUSIONS AND RELEVANCE: For facial injections of neurotoxin in saline, 30-gauge needles were associated with greater incidence of clinically significant pain than 32-gauge needles. For patients prone to experience clinically significant pain with facial injections, use of 32-gauge needles may minimize this discomfort. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01981174.

Evaluation of oxidative stress markers in aqueous humor of primary open angle glaucoma and primary angle closure glaucoma patients.

PURPOSE: The present study was designed to determine the levels of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and non-enzymatic antioxidants (vitamins C and E) in aqueous humor of primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG) patients. MATERIALS AND METHODS: In this study, aqueous humor of POAG (n = 30) and PACG (n = 30) patients was obtained. For control, aqueous humor of 30 age-matched cataract patients (n = 30) was collected. Activities of antioxidant enzymes and non-enzymatic antioxidants levels were measured spectrophotometrically. RESULTS: A significant increase in superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities was found in aqueous humor of POAG and PACG patients as compared to cataract patients (p < 0.001). No significant changes were observed in catalase activity. The levels of vitamins C and E were significantly lower in the aqueous humor of POAG and PACG as compared to cataract patients (p < 0.001). CONCLUSION: These results suggest that a significant increase in oxidative stress may play a role in the pathogenesis of POAG and PACG. Determination of oxidative stress in aqueous humor may help in understanding the course of this disease, and oxidative damage might be a relevant target for both prevention and therapy.

Scanning electron microscopy of the trabecular meshwork: understanding the pathogenesis of primary angle closure glaucoma.

PURPOSE: To study ultrastructural changes of the trabecular meshwork in acute and chronic primary angle closure glaucoma (PACG) and primary open angle glaucoma (POAG) eyes by scanning electron microscopy. MATERIALS AND METHODS: Twenty-one trabecular meshwork surgical specimens from consecutive glaucomatous eyes after a trabeculectomy and five postmortem corneoscleral specimens were fixed immediately in Karnovsky solution. The tissues were washed in 0.1 M phosphate buffer saline, post-fixed in 1% osmium tetraoxide, dehydrated in acetone series (30-100%), dried and mounted. RESULTS: Normal trabecular tissue showed well-defined, thin, cylindrical uveal trabecular beams with many large spaces, overlying flatter corneoscleral beams and numerous smaller spaces. In acute PACG eyes, the trabecular meshwork showed grossly swollen, irregular trabecular endothelial cells with intercellular and occasional basal separation with few spaces. Numerous activated macrophages, leucocytes and amorphous debris were present. Chronic PACG eyes had a few, thickened posterior uveal trabecular beams visible. A homogenous deposit covered the anterior uveal trabeculae and spaces. Converging, fan-shaped trabecular beam configuration corresponded to gonioscopic areas of peripheral anterior synechiae. In POAG eyes, anterior uveal trabecular beams were thin and strap-like, while those posteriorly were wide, with a homogenous deposit covering and bridging intertrabecular spaces, especially posteriorly. Underlying corneoscleral trabecular layers and spaces were visualized in some areas. CONCLUSIONS: In acute PACG a marked edema of the endothelium probably contributes for the acute and marked intraocular pressure (IOP) elevation. Chronically raised IOP in chronic PACG and POAG probably results, at least in part, from decreased aqueous outflow secondary to widening and fusion of adjacent trabecular beams, together with the homogenous deposit enmeshing trabecular beams and spaces.

Rieger syndrome with multiple chromosomal breaks and chromosome 4 deletion.

Rieger syndrome (RS) is a rare autosomal dominant disorder with variable expressivity and complete penetrance. Axenfeld-Rieger syndrome (ARS) shows genetic heterogeneity with mutations in several chromosomal loci being implicated including PITX2, FOXC1 and PAX6. Cytogenetic analysis was done in this case. Patient had de novo 46,XY,del(4q25-q27) karyotype with a high percentage (>35%) of chromosomal breaks. The breaks were on different chromosomes and not related to disease phenotype of RS. Such chromosomal breaks are diagnostic of chromosomal instability syndromes. Available literature does not report chromosomal breaks in RS or due to culture condition. Such a high percentage of chromosomal breaks are associated with development of certain cancers. In the present case we did not find any features consistent with any of the chromosomal instability syndromes like Fanconi's anaemia and Blooms syndrome, but such cases need to be under regular follow-up. Thus RS cases with multiple chromosomal breaks need regular follow-up and genetic counselling.