TRESK channel contribution to nociceptive sensory neurons excitability: modulation by nerve injury

Background: Neuronal hyperexcitability is a crucial phenomenon underlying spontaneous and evoked pain. In invertebrate nociceptors, the S-type leak K(+) channel (analogous to TREK-1 in mammals) plays a critical role of in determining neuronal excitability following nerve injury. Few data are available on the role of leak K(2P) channels after peripheral axotomy in mammals. Results: Here we describe that rat sciatic nerve axotomy induces hyperexcitability of L4-L5 DRG sensory neurons and decreases TRESK (K2P18.1) expression, a channel with a major contribution to total leak current in DRGs. While the expression of other channels from the same family did not significantly change, injury markers ATF3 and Cacna2d1 were highly upregulated. Similarly, acute sensory neuron dissociation (in vitro axotomy) produced marked hyperexcitability and similar total background currents compared with neurons injured in vivo. In addition, the sanshool derivative IBA, which blocked TRESK currents in transfected HEK293 cells and DRGs, increased intracellular calcium in 49% of DRG neurons in culture. Most IBA-responding neurons (71%) also responded to the TRPV1 agonist capsaicin, indicating that they were nociceptors. Additional evidence of a biological role of TRESK channels was provided by behavioral evidence of pain (flinching and licking), in vivo electrophysiological evidence of C-nociceptor activation following IBA injection in the rat hindpaw, and increased sensitivity to painful pressure after TRESK knockdown in vivo. Conclusions: In summary, our results clearly support an important role of TRESK channels in determining neuronal excitability in specific DRG neurons subpopulations, and show that axonal injury down-regulates TRESK channels, therefore contributing to neuronal hyperexcitability

TRESK channel contribution to nociceptive sensory neurons excitability: modulation by nerve injury

<p>Abstract</p> <p>Background</p> <p>Neuronal hyperexcitability is a crucial phenomenon underlying spontaneous and evoked pain. In invertebrate nociceptors, the S-type leak K⁺channel (analogous to TREK-1 in mammals) plays a critical role of in determining neuronal excitability following nerve injury. Few data are available on the role of leak K_2Pchannels after peripheral axotomy in mammals.</p> <p>Results</p> <p>Here we describe that rat sciatic nerve axotomy induces hyperexcitability of L4-L5 DRG sensory neurons and decreases TRESK (K2P18.1) expression, a channel with a major contribution to total leak current in DRGs. While the expression of other channels from the same family did not significantly change, injury markers ATF3 and Cacna2d1 were highly upregulated. Similarly, acute sensory neuron dissociation (<it>in vitro </it>axotomy) produced marked hyperexcitability and similar total background currents compared with neurons injured <it>in vivo</it>. In addition, the sanshool derivative IBA, which blocked TRESK currents in transfected HEK293 cells and DRGs, increased intracellular calcium in 49% of DRG neurons in culture. Most IBA-responding neurons (71%) also responded to the TRPV1 agonist capsaicin, indicating that they were nociceptors. Additional evidence of a biological role of TRESK channels was provided by behavioral evidence of pain (flinching and licking), in vivo electrophysiological evidence of C-nociceptor activation following IBA injection in the rat hindpaw, and increased sensitivity to painful pressure after TRESK knockdown in vivo.</p> <p>Conclusions</p> <p>In summary, our results clearly support an important role of TRESK channels in determining neuronal excitability in specific DRG neurons subpopulations, and show that axonal injury down-regulates TRESK channels, therefore contributing to neuronal hyperexcitability.</p

Clinical assessment instruments validated for nursing practice in the Italian context: a systematic review of the literature

Aims. With the aim to identify the instruments validated for Italian nursing practice, a systematic review of the literature was undertaken.Results. A total of 101 instruments emerged. The majority (89; 88.1%) were developed in other countries; the remaining (14; 13.9%) were developed and validated in the Ital-ian context. The instruments were developed to measure patient’s problems (63/101; 62.4%), outcomes (27/101; 26.7%), risks (4/101; 4%) and others issues (7/101; 6.9%). The majority of participants involved in the validation processes were younger adults (49; 48.5%), older adults (40; 39.5%), children (4; 4%), adolescents (3; 3%), and children/adolescents (1; 1%). The instruments were structured primarily in the form of questionnaires (61; 60.4%), as a grid for direct observation (27; 26.7%) or in other forms (12; 11.9%). Among the 101 instruments emerged, there were 1 to 7 validation measures documented with on average 3.2 (95% CI 2.86-3.54) for each instrument.Conclusions. Developing validation studies giving priority to those instruments widely adopted in the clinical nursing practice is recommended.  

Three-dimensional conformal radiotherapy, static intensity-modulated and helical intensity-modulated radiotherapy in glioblastoma. Dosimetric comparison in patients with overlap between target volumes and organs at risk.

Aims and background. Radiotherapy is the standard treatment of glioblastoma. Three-dimensional conformal radiotherapy is the standard technique to treat glioblastoma. Intensity-modulated radiotherapy and helical intensity-modulated radiotherapy (tomotherapy) are becoming widely used. The present study compared three-dimensional conformal radiotherapy, intensity-modulated radiotherapy and tomotherapy in terms of target coverage and preservation of organs at risk.Methods. Ten patients treated with three-dimensional conformal radiotherapy, with a target volume close to or superimposed to the organs at risk, were retrospectively selected. The plans were re-planned with step-and-shoot 3/5 fields intensity-modulated radiotherapy and tomotherapy. Target coverage and sparing of organs at risk were statistically compared. Results. Mean planning target volume V95% improved with sophisticated techniques (87.2%, 93.2%, 97.6% with three-dimensional conformal radiotherapy, intensity-modulated radiotherapy and tomotherapy, respectively). The comparison of three-dimensional conformal radiotherapy and intensity-modulated radiotherapy did not show significant differences, whereas differences were significant when three-dimensional conformal radiotherapy and tomotherapy as well as intensity-modulated radiotherapy and tomotherapy were compared. Mean planning target volume/clinical target volume D99-D98-D95 were not different between three-dimensional conformal radiotherapy and intensity-modulated radiotherapy, but they were different between tomotherapy and three-dimensional conformal radiotherapy and intensity-modulated radiotherapy, with better clinical target volume/and planning target volume coverage with the tomotherapy plans. Brain D33/66 were 31.1/11.8 Gy, 37.5/18.3 Gy and 28.5/14.7 Gy with three-dimensional conformal radiotherapy, intensity-modulated radiotherapy and tomotherapy, respectively. Mean brainstem, optic nerves and chiasma Dmax were always within the defined constraints. The homogeneity index improved with intensity-modulated radiotherapy/tomotherapy compared to three-dimensional conformal radiotherapy. Tomotherapy was better than intensity-modulated radiotherapy in all patients. Conclusions. In this selected group of patients, a significant dosimetric advantage was evident for tomotherapy compared with three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. Significant advantages were evident in terms of panning target volume coverage (V95), D99, D98 and D95. The clinical significance of the results should be defined

Prevalence and incidence density of unavoidable pressure ulcers in elderly patients admitted to medical units

To describe the prevalence and incidence density of hospital-acquired unavoidable pressure sores among patients aged 6565 years admitted to acute medical units. A secondary analysis of longitudinal study data collected in 2012 and 2013 from 12 acute medical units located in 12 Italian hospitals was performed. Unavoidable pressure ulcers were defined as those that occurred in haemodynamically unstable patients, suffering from cachexia and/or terminally ill and were acquired after hospital admission. Data at patient and at pressure ulcer levels were collected on a daily basis at the bedside by trained researchers. A total of 1464 patients out of 2080 eligible (70.4%) were included. Among these, 96 patients (6.5%) hospital-acquired a pressure ulcer and, among 19 (19.7%) were judged as unavoidable. The incidence of unavoidable pressure ulcer was 8.5/100in hospital-patient days. No statistically significant differences at patient and pressure ulcers levels have emerged between those patients that acquired unavoidable and avoidable pressure sores. Although limited, evidence on unavoidable pressure ulcer is increasing. More research in the field is recommended to support clinicians, managers and policymakers in the several implications of unavoidable pressure ulcers both at the patient and at the system levels

Prevalence and incidence density of unavoidable pressure ulcers in elderly patients admitted to medical units

To describe the prevalence and incidence density of hospital-acquired unavoidable pressure sores among patients aged 6565 years admitted to acute medical units. A secondary analysis of longitudinal study data collected in 2012 and 2013 from 12 acute medical units located in 12 Italian hospitals was performed. Unavoidable pressure ulcers were defined as those that occurred in haemodynamically unstable patients, suffering from cachexia and/or terminally ill and were acquired after hospital admission. Data at patient and at pressure ulcer levels were collected on a daily basis at the bedside by trained researchers. A total of 1464 patients out of 2080 eligible (70.4%) were included. Among these, 96 patients (6.5%) hospital-acquired a pressure ulcer and, among 19 (19.7%) were judged as unavoidable. The incidence of unavoidable pressure ulcer was 8.5/100 in hospital-patient days. No statistically significant differences at patient and pressure ulcers levels have emerged between those patients that acquired unavoidable and avoidable pressure sores. Although limited, evidence on unavoidable pressure ulcer is increasing. More research in the field is recommended to support clinicians, managers and policymakers in the several implications of unavoidable pressure ulcers both at the patient and at the system levels

Clinical assessment instruments validated for nursing practice in the Italian context: a systematic review of the literature

Aims. With the aim to identify the instruments validated for Italian nursing practice, a systematic review of the literature was undertaken. Results. A total of 101 instruments emerged. The majority (89; 88.1%) were developed in other countries; the remaining (14; 13.9%) were developed and validated in the Italian context. The instruments were developed to measure patient’s problems (63/101; 62.4%), outcomes (27/101; 26.7%), risks (4/101; 4%) and others issues (7/101; 6.9%). The majority of participants involved in the validation processes were younger adults (49; 48.5%), older adults (40; 39.5%), children (4; 4%), adolescents (3; 3%), and children/adolescents (1; 1%). The instruments were structured primarily in the form of questionnaires (61; 60.4%), as a grid for direct observation (27; 26.7%) or in other forms (12; 11.9%). Among the 101 instruments emerged, there were 1 to 7 validation measures documented with on average 3.2 (95% CI 2.86-3.54) for each instrument. Conclusions. Developing validation studies giving priority to those instruments widely adopted in the clinical nursing practice is recommended

Clinical assessment instruments validated for nursing practice in the Italian context: a systematic review of the literature

AIMS: With the aim to identify the instruments validated for Italian nursing practice, a systematic review of the literature was undertaken.RESULTS: A total of 101 instruments emerged. The majority (89; 88.1%) were developed in other countries; the remaining (14; 13.9%) were developed and validated in the Italian context. The instruments were developed to measure patient's problems (63/101; 62.4%), outcomes (27/101; 26.7%), risks (4/101; 4%) and others issues (7/101; 6.9%). The majority of participants involved in the validation processes were younger adults (49; 48.5%), older adults (40; 39.5%), children (4; 4%), adolescents (3; 3%), and children/adolescents (1; 1%). The instruments were structured primarily in the form of questionnaires (61; 60.4%), as a grid for direct observation (27; 26.7%) or in other forms (12; 11.9%). Among the 101 instruments emerged, there were 1 to 7 validation measures documented with on average 3.2 (95% CI 2.86-3.54) for each instrument.CONCLUSIONS: Developing validation studies giving priority to those instruments widely adopted in the clinical nursing practice is recommended

Clinical assessment instruments validated for nursing practice in the Italian context: a systematic review of the literature

Aims. With the aim to identify the instruments validated for Italian nursing practice, a systematic review of the literature was undertaken. Results. A total of 101 instruments emerged. The majority (89; 88.1%) were developed in other countries; the remaining (14; 13.9%) were developed and validated in the Italian context. The instruments were developed to measure patient\u2019s problems (63/101; 62.4%), outcomes (27/101; 26.7%), risks (4/101; 4%) and others issues (7/101; 6.9%). The majority of participants involved in the validation processes were younger adults (49; 48.5%), older adults (40; 39.5%), children (4; 4%), adolescents (3; 3%), and children/adolescents (1; 1%). The instruments were structured primarily in the form of questionnaires (61; 60.4%), as a grid for direct observation (27; 26.7%) or in other forms (12; 11.9%). Among the 101 instruments emerged, there were 1 to 7 validation measures documented with on average 3.2 (95% CI 2.86-3.54) for each instrument. Conclusions. Developing validation studies giving priority to those instruments widely adopted in the clinical nursing practice is recommended

Clinical assessment instruments validated for nursing practice in the Italian context: a systematic review of the literature

Aims. With the aim to identify the instruments validated for Italian nursing practice, a systematic review of the literature was undertaken. Results. A total of 101 instruments emerged. The majority (89; 88.1%) were developed in other countries; the remaining (14; 13.9%) were developed and validated in the Italian context. The instruments were developed to measure patient’s problems (63/101; 62.4%), outcomes (27/101; 26.7%), risks (4/101; 4%) and others issues (7/101; 6.9%). The majority of participants involved in the validation processes were younger adults (49; 48.5%), older adults (40; 39.5%), children (4; 4%), adolescents (3; 3%), and children/adolescents (1; 1%). The instruments were structured primarily in the form of questionnaires (61; 60.4%), as a grid for direct observation (27; 26.7%) or in other forms (12; 11.9%). Among the 101 instruments emerged, there were 1 to 7 validation measures documented with on average 3.2 (95% CI 2.86-3.54) for each instrument. Conclusions. Developing validation studies giving priority to those instruments widely adopted in the clinical nursing practice is recommended