Ca2+ transients in astrocyte fine processes occur via Ca2+ influx in the adult mouse hippocampus

Astrocytes display complex morphologies with an array of fine extensions extending from the soma and the primary thick processes. Until the use of genetically encoded calcium indicators (GECIs) selectively expressed in astrocytes, Ca²⁺ signaling was only examined in soma and thick primary processes of astrocytes where Ca²⁺‐sensitive fluorescent dyes could be imaged. GECI imaging in astrocytes revealed a previously unsuspected pattern of spontaneous Ca²⁺ transients in fine processes that has not been observed without chronic expression of GECIs, raising potential concerns about the effects of GECI expression. Here, we perform two‐photon imaging of Ca²⁺ transients in adult CA1 hippocampal astrocytes using a new single‐cell patch‐loading strategy to image Ca²⁺‐sensitive fluorescent dyes in the cytoplasm of fine processes. We observed that astrocyte fine processes exhibited a high frequency of spontaneous Ca²⁺ transients whereas astrocyte soma rarely showed spontaneous Ca²⁺ oscillations similar to previous reports using GECIs. We exploited this new approach to show these signals were independent of neuronal spiking, metabotropic glutamate receptor (mGluR) activity, TRPA1 channels, and L‐ or T‐type voltage‐gated calcium channels. Removal of extracellular Ca²⁺ almost completely and reversibly abolished the spontaneous signals while IP₃R2 KO mice also exhibited spontaneous and compartmentalized signals, suggesting they rely on influx of extracellular Ca²⁺. The Ca²⁺ influx dependency of the spontaneous signals in patch‐loaded astrocytes was also observed in astrocytes expressing GCaMP3, further highlighting the presence of Ca²⁺ influx pathways in astrocytes. The mechanisms underlying these localized Ca²⁺ signals are critical for understanding how astrocytes regulate important functions in the adult brain. GLIA 2016;64:2093–2103     

Suicide rates in five-year age-bands after the age of 60 years: the international landscape†

Background: There is paucity of studies examining suicide rates in narrow five-year age-bands after the age of 60 years. This study examined suicide rates in eight five-year age-bands between the age of 60 and 99 years because this will allow more precise comparison between the young old (60–79 years) and the oldest old (80+ years) age groups.

Methods: Data on the number of suicides (International Classification of Diseases – ICD-10 codes, X60-84) in each of the eight five-year age-bands between the age-bands 60–64 years and 95–99 years in both gender for as many years as possible from 2000 were ascertained from three sources: colleagues with access to national data, national statisics office websites and email contact with the national statistics offices. The population size for the corresponding years and age-bands was estimated for each country using data provided by the United Nations website.

Results: In men, suicide rates continued to increase for each of the seven five-year age-bands from 60–64 years to 90–94 years age-band, and then declined slightly for the 95–99 year age-band. In women, suicide rates continued to increase for each of the six five-year age-bands from 60–64 years to 85–89 years age-bands, and then declined slightly for the 90–94 years and 95–99 years age-bands.

Conclusions: The overall global suicide rates for each of the eight five-year age-bands are sufficiently large for them to constitute a public health concern. This is especially important given the ongoing rise in the elderly population size and the paucity of data on risk and protective factors for suicide in the five-year age-bands after the age of 60 years.     

Is laparoscopic surgery for recurrent Crohn’s disease beneficial in patients with previous primary resection through midline laparotomy? A case-matched study

Background

Patients undergoing abdominal surgery for Crohn??s disease are predisposed to recurrence requiring reoperation. The effectiveness of laparoscopic versus open resection in patients with previous intestinal resection for Crohn??s through midline laparotomy is controversial.

Methods

Patients with previous open resection for intestinal Crohn??s disease undergoing elective laparoscopic surgery for recurrent bowel disease from 1997 to 2011 were case-matched with open counterparts based on age (±5?years), gender, body mass index (±2?kg/m²), American Society of Anesthesiologists (ASA) score, surgical procedure, and year of surgery (±3?years). Groups were compared using Chi-square or Fisher exact tests for categorical and the Wilcoxon rank-sum test for quantitative data.

Results

26 patients undergoing laparoscopic ileocolectomy (n?=?14), proctocolectomy (n?=?5), small bowel resection (n?=?4), abdominoperineal resection (n?=?1), extended right colectomy (n?=?1), and strictureplasty (n?=?1) were well matched to 26 patients undergoing open surgery. The number of previous operations, disease phenotypes, steroid use, and comorbidities were comparable in the two groups. There were no deaths, and three patients (12?%) required conversion because of adhesions. Laparoscopic and open groups had statistically similar operating times (169 versus 158?min, p?=?0.94), estimated blood loss (222 versus 427?ml, p?=?0.32), overall morbidity (39 versus 69?%, p?=?0.051), reoperation rates (8 versus 0?%, p?=?0.5), postoperative return of bowel function (3.5?±?1.4 versus 3.9?±?1.7?days, p?=?0.3), mean length of hospital stay (6.4?±?6.2 versus 6.9?±?3.5?days, p?=?0.12), and readmission rates (8 versus 12?%, p?=?0.64). Wound infection rate was decreased after laparoscopic surgery (0 versus 27?%, p?=?0.01).

Conclusions

Surgery for recurrent Crohn??s disease in patients with previous primary resection through laparotomy can be frequently and safely completed laparoscopically. Wound infection rates are reduced, but the recovery advantages of a minimally invasive approach are not maintained when compared with open surgery. The decision to operate laparoscopically should therefore be carefully calibrated.     

Proximal femoral fractures: Principles of management and review of literature

PurposeThe purpose of this study was to review the principles involved in the management of proximal femoral fractures as reported in the literature. Methods: A medical literature search in the MEDLINE (PubMed) and Cochrane database was undertaken to review strategies and principles in proximal femoral fracture treatment. Randomized control trials and meta analysis were given preference while case reports/small series were rejected. Results and conclusions: Early anatomical reduction and surgical fixation remains the best option to reduce the risk of complications like non-union and avascular necrosis in treating fracture neck femurs. Cancellous screws continue to be the preferred treatment for fixation of neck femur fractures in younger population until the benefit of using sliding hip screws is validated by large multicentric studies. In the geriatric age group, early prosthetic replacement brings down the mortality and morbidity associated with neck femur fractures. Sliding hip screw (DHS) is the best available option for stable inter trochanteric fractures. The use of intramedullary nails e.g. PFN is beneficial in treating inter trochanteric fractures with comminution and loss of lateral buttress. Intramedullary implants have been proven to have increased success rates in subtrochanteric fractures and should be preferred over extramedullary plate fixation systems.     

Bioavailable vitamin D is more tightly linked to mineral metabolism than total vitamin D in incident hemodialysis patients

Prior studies showed conflicting results regarding the association between 25-hydroxyvitamin D (25(OH)D) levels and mineral metabolism in end-stage renal disease. In order to determine whether the bioavailable vitamin D (that fraction not bound to vitamin D-binding protein) associates more strongly with measures of mineral metabolism than total levels, we identified 94 patients with previously measured 25(OH)D and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) from a cohort of incident hemodialysis patients. Vitamin D-binding protein was measured from stored serum samples. Bioavailable 25(OH)D and 1,25(OH)(2)D were determined using previously validated formulae. Associations with demographic factors and measures of mineral metabolism were examined. When compared with whites, black patients had lower levels of total, but not bioavailable, 25(OH)D. Bioavailable, but not total, 25(OH)D and 1,25(OH)(2)D were each significantly correlated with serum calcium. In univariate and multivariate regression analysis, only bioavailable 25(OH)D was significantly associated with parathyroid hormone levels. Hence, bioavailable vitamin D levels are better correlated with measures of mineral metabolism than total levels in patients on hemodialysis.     

Is Adjuvant Chemotherapy Really Needed After Curative Surgery for Rectal Cancer Patients Who are Node-Negative After Neoadjuvant Chemoradiotherapy?

Purpose  

Adjuvant chemotherapy is currently offered, as standard, after curative resection for patients with rectal cancer who receive neoadjuvant chemoradiation (NCRT). We postulate that adjuvant chemotherapy adds minimal oncologic benefit for patients who undergo total mesorectal excision who are node-negative after neoadjuvant chemoradiation.     

Quality of life improves within 30 days of surgery for Crohn's disease

BACKGROUND: The effect of surgery on quality of life (QOL) in the early postoperative period is important in Crohn's disease because of the multiple surgical procedures that patients undergo and the acute QOL benefits that might occur as a result of modifications of medical treatment. Earlier studies of the effect of surgery on QOL have been retrospective and assessed changes 3 to 24 months after surgery. This study prospectively assesses the effect of surgery on QOL in the early postoperative period. STUDY DESIGN: Patients requiring surgical management of sequelae of Crohn's disease were obtained from a prospectively entered database including data on QOL. Preoperative and 30-day postoperative QOL were determined in 82 patients using Cleveland Global Quality of Life (CGQL) scores (range from 0 [worst] to 10 [best possible] QOL). Preoperative and postoperative scores were compared using a paired t-test to determine the significance of any change in QOL after surgery. The effect of other variables on change in QOL after surgery was assessed using the t-test or analysis of variance. Multifactor analysis of variance was used to assess the effect of several independent variables. RESULTS: Eighty-two patients (41 women) of 142 patients who had had surgery (58%) had complete preoperative and 30-day postoperative scores. The incidence of complications was 23% (11% were major). There was a significant improvement in QOL 30 days after surgery as measured by CGQL (0.6 +/- 0.2 preoperative to 0.7 +/- 0.2 postoperative; mean +/- SD; p < 0.001). The mean preoperative CGQL was 0.56 +/- 0.24 and the mean improvement was 0.11 +/- 0.20 toward a better QOL. Female patients (p < 0.05) and those who did not develop complications within 30 days of surgery (p < 0.05) had a significantly greater improvement in CGQL after surgery than other groups. No other factor was predictive of improved outcomes. CONCLUSIONS: QOL as measured by CGQL improves early after surgery (30 days postoperatively). Improvement in CGQL is greater in female patients and patients who do not develop complications in the postoperative period. It is not affected by other patient characteristics, nature of disease, indication, or procedure performed. Most patients who undergo surgery for Crohn's disease feel that surgery has helped them and would undergo surgery again.     

Altered ATP-dependent mitochondrial Ca2+ uptake in cold ischemia is attenuated by ruthenium red

BACKGROUND: Graft dysfunction as a result of preservation injury remains a major clinical problem in liver transplantation. This is related in part to accumulation of mitochondrial calcium (Ca(2+)), which has been linked to activation of proapoptotic factors. We hypothesized that cold ischemia increases mitochondrial Ca(2+) uptake in a concentration dependent fashion and that ruthenium red (RR) will attenuate these changes by inhibiting the mitochondrial Ca(2+) uniporter. METHODS: Rat livers perfused with cold University of Wisconsin (UW) solution (4 degrees C) with or without RR (10 microM) via the portal vein (n = 3 per group) were processed immediately (no ischemia) or after 24 h cold-storage (24 h cold ischemia). Mitochondria were separated by differential centrifugation, and adenosine triphosphate (ATP)-dependent (45)Ca(2+) uptake was determined in the presence of ATP (5 mM), adenosine diphosphate (ADP), or adenosine 5'-beta,gamma-imidotriphosphate (AMP-PNP); variable concentrations of extramitochondrial (45)Ca(2+) were used. All measurements were performed in triplicate. Student's t test with P < 0.05 was taken as significant. RESULTS: Our data demonstrate the following: 1) ATP-dependent (45)Ca(2+) uptake in mitochondria separated from livers following 24 h of cold ischemia in UW alone was higher than in mitochondria isolated from non-ischemic livers; the increased uptake was dependent on the concentration of (45)Ca(2+) in the incubation buffer. 2) There was no difference in ATP-dependent (45)Ca(2+) uptake between nonischemic mitochondria and those separated from livers stored in UW-RR for 24 h. 3) (45)Ca(2+) uptake in mitochondria from livers subjected to 24 h of cold ischemia in UW-RR was significantly lower compared to those from livers stored in UW alone when (45)Ca(2+) concentrations were greater than 1 microM. CONCLUSION: 1) Cold ischemia affects mitochondrial Ca(2+) handling, especially when it is challenged by high extramitochondrial Ca(2+) concentrations. 2) The addition of RR in preservation solution attenuates the effects of cold ischemia on mitochondrial Ca(2+) handling. 3) Inhibition of mitochondrial Ca(2+) uniporter with RR protects mitochondria from Ca(2+) overload at high Ca(2+) concentrations. These findings may offer a potentially effective strategy for prevention of ischemia-reperfusion injury in liver transplantation.     

Estimation of stature from hand dimensions of north and south Indians

The present study was undertaken to predict the stature of a person using hand length and breadth. The study includes 500 right-hand dominant medical students aged between 20 and 30 years, from northern and southern parts of India, studying in Kasturba medical college, Manipal, India. Hand length was measured 'between the distal wrist crease and the tip of middle finger (HL-1)' and 'between the mid-point of inter-styloid line to the tip of middle finger (HL-2)'. Hand breadth was measured between radial side of the second metacarpophalyngeal joint and ulnar side of the fifth metacarpophalyngeal joint (HB). No significant difference was present in hand dimensions between north and south Indians. When compared between both hands, right-hand dimensions were larger than the left hand, with statistically significant difference in HL-2 and HB. Linear regression equations using hand length is more helpful in estimating stature than the hand breadth. The correlation coefficients ranged from 0.673 to 0.665 and 0.740 to 0.732 in north Indian males and females, respectively. Whereas in south Indians, it ranged from 0.752 to 0.732 and 0.701 to 0.691 in males and females, respectively. Multiple regression equations give better results than linear regression equations. HL-2 gives more accurate results in stature estimation than the HL-1.     

Role of posterior stabilisation in the management of tuberculosis of the dorsal and lumbar spine

We present a prospective study of patients with tuberculosis of the dorsal, dorsolumbar and lumbar spine after combined anterior (radical debridement and anterior fusion) and posterior (instrumentation and fusion) surgery. The object was to study the progress of interbody union, the extent of correction of the kyphosis and its maintenance with early mobilisation, and the incidence of graft and implant-related problems. The American Spinal Injury Association (ASIA) score was used to assess the neurological status. The mean preoperative vertebral loss was highest (0.96) in the dorsal spine. The maximum correction of the kyphosis in the dorsolumbar spine was 17.8 degrees. Loss of correction was maximal in the lumbosacral spine at 13.7 degrees. All patients had firm anterior fusion at a mean of five months. The incidence of infection was 3.9% and of graft-related problems 6.5%. We conclude that adjuvant posterior stabilisation allows early mobilisation and rehabilitation. Graft-related problems were fewer and the progression and maintenance of correction of the kyphosis were better than with anterior surgery alone. There is no additional risk relating to the use of an implant either posteriorly or anteriorly even when large quantities of pus are present.