Critical limb ischaemia in the time of COVID-19: establishing ambulatory service provision.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic enforced changes to healthcare services at a pace and extent not seen previously in the NHS. The Royal Devon and Exeter provides regional vascular surgery services. A consultant-led urgent 'hot clinic' was established, providing patients with ambulatory care. We aim to describe the service for critical limb ischaemia (CLI) before and during the COVID-19 pandemic, and evaluate this against recommended best practice. METHODS: Retrospective review of electronic databases and records of patients with CLI during a non-COVID vs COVID-19 period. Primary outcome measures were those established by guidance from the Vascular Society of Great Britain and Ireland. RESULTS: Non-COVID vs COVID-19: total patients n=97 vs 96, of which CLI patients n=29 vs 21. Median length of stay 15 vs 0 days (p<0.001); median time from referral to specialist review 0 vs 3 days (p<0.001); multidisciplinary team meeting (MDT) recorded 3% vs 29%; median time to intervention 6 vs 8 days; conservative management 52% vs 67%; endovascular 28% vs 10%; open surgery 21% vs 24%; 30-day survival 79% vs 76%. CONCLUSION: COVID-19 imposed a major change to the service for patients with CLI with a focus on ambulatory care pathways for diagnosis and intervention. We observe a significant reduction in overall length of stay with no clinically significant change in time to consultant review, time to imaging, overall management strategy or outcomes. The results of this study show that patients with CLI can be managed safely and effectively on an ambulatory basis in accordance with established best practice.

"I feel as if I'm lying to them": Exploring Lesbian Muslims' Experiences of Rejection, Support, and Depression.

The current exploratory study utilized a mixed-methods design to study 18 lesbian Muslims' mental health in relation to familial and online social support (M Age = 24, Sd = 9). Due to the threat of familial rejection, the majority of participants (n = 11) selectively disclosed their sexual identity and four participants publicly disclosed. Half of participants scored as mildly to severely depressed on the Beck Depression Inventory (M = 15, Sd = 9). Participants reporting changes in their familial relationships due to their sexual orientation scored as the most highly depressed, F (2, 15) = 4.75, p = .025. Participants' depression scores varied significantly between those that belonged to online support groups addressing religion and sexuality (n = 8, M = 8.712, SD = 6.183) and those that did not (n = 10, M = 20.250, SD = 7.772), t(16) = 3.416, p = .004. Future research would benefit from exploring how therapeutic alliances and family of choice networks can help buffer lesbian Muslims' experiences of familial rejection.

Suspected appendicitis and COVID-19, a change in investigation and management-a multicentre cohort study.

PURPOSE: The COVID-19 pandemic has reformed global healthcare delivery. On 25 March 2020, Intercollegiate guidelines were published in the UK to promote safe surgical provision during the COVID-19 outbreak advocating non-operative management or avoidance of laparoscopy when surgery is essential. The effects of this on the investigation and management of appendicitis remain unknown. METHODS: We performed a multicentre, prospective, observational study from the start of the new guidelines to the 6th of May 2020. We included all patients referred to surgical teams with suspected appendicitis. A recent historical cohort was identified for comparison. The primary outcome was the impact of the COVID-19 pandemic on the use of non-operative management in appendicitis. Secondary outcomes included imaging, negative appendicectomy rate (NAR), length of stay (LOS) and 30-day complications. RESULTS: A total of 63/164 (38%) patients compared to 79/191 (41%) were diagnosed with appendicitis before and after the guidelines were introduced (p = 0.589). CT scanning increased (71/164 vs 105/191; p = 0.033) while ultrasound scanning decreased (71/164 vs 62/191; p = 0.037). Appendicitis was more likely to be managed non-operatively (11/63 vs 51/79; p < 0.001) and, of those managed surgically, with an open approach (3/52 vs 26/28 p < 0.001). The NAR also reduced (5/52 vs 0/28; p = 0.157). LOS was shorter in non-operatively managed patients (1 day vs 3 days; p < 0.001) without a difference in complications (10/51 vs 4/28; p = 0.760). CONCLUSION: Introduction of the guidelines was associated with changes in practice. Despite these changes, short-term complications did not increase and LOS decreased. Questions remain on the longer-term complication rates in non-operatively managed patients.

Lack of correlation between left ventricular outflow tract velocity time integral and stroke volume index in mechanically ventilated patients / Ausencia de correlación entre la integral velocidad tiempo en el tracto de salida del ventrículo izquierdo y el índice volumen sistólico en pacientes en ventilación mecánica

Objective: To assess the correlation between left ventricular outflow tract velocity time integral (LVOT VTI) and stroke volume index (SVI) calculated by thermodilution methods in ventilated critically ill patients. Design: A prospective, descriptive, multicenter study was performed. Setting: Five intensive care units from university hospitals. Patients: Patients older than 17 years needing mechanical ventilation and invasive hemodynamic monitoring were included. Interventions: LVOT VTI was measured by pulsatile Doppler echocardiography. Calculations of SVI were performed through a floating pulmonary artery catheter (PAC) or a Pulse index Contour Cardiac Output (PiCCO(R)) thermodilution methods. Main variables: The relation between LVOT VTI and SVI was tested by linear regression analysis. Results: One hundred and fifty-six paired measurements were compared. Mean LVOT VTI was 20.83±4.86cm and mean SVI was 41.55±9.55mL/m2. Pearson correlation index for these variables was r=0.644, p<0.001; ICC was 0.52 (CI 95% 0.4-0.63). When maximum LVOT VTI was correlated with SVI, Pearson correlation index was r=0.62, p<0.001. Correlation worsened for extreme values, especially for those with higher LVOT VTI. Conclusions: LVOT VTI could be a complementary hemodynamic evaluation in selected patients, but does not eliminate the need for invasive monitoring at the present time. The weak correlation between LVOT VTI and invasive monitoring deserves additional assessment to identify the factors affecting this disagreement

Objetivo: Evaluar la correlación entre la integral velocidad tiempo del tracto de salida del ventrículo izquierdo (IVT TSVI) y el índice volumen sistólico (IVS) calculado por métodos de termodilución en pacientes ventilados críticamente enfermos. Diseño: Se realizó un estudio prospectivo, descriptivo y multicéntrico. Ámbito: Cinco unidades de cuidados intensivos de hospitales universitarios. Pacientes: Se incluyeron pacientes mayores de 17 años que necesitaron ventilación mecánica y monitorización hemodinámica invasiva. Intervenciones: La IVT TSVI se midió mediante Doppler pulsátil. Los cálculos de SVI se realizaron a través de un catéter de arteria pulmonar (CAP) o un método de Pulse index Contour Cardiac Output (PiCCO(R)), con métodos de termodilución. Variables principales: La relación entre IVT TSVI e IVS se evaluó mediante análisis de regresión lineal. Resultados: Se compararon 156 mediciones pareadas. La IVT TSVI media fue de 20,83±4,86cm y la media de IVS fue de 41,55±9,55ml/m2. El índice de correlación de Pearson para estas variables fue r=0,644, p<0,001; ICC fue 0,52 (IC 95%: 0,4-0,63). Cuando la IVT TSVI máxima se correlacionó con el IVS, el índice de correlación de Pearson fue r=0,62, p<0,001. La correlación empeoró para los valores extremos, especialmente para aquellos con mayor IVT TSVI. Conclusiones: La IVT TSVI podría ser una evaluación hemodinámica complementaria en pacientes seleccionados, pero no elimina la necesidad de un control invasivo en la actualidad. La débil correlación entre la IVT TSVI y la monitorización invasiva requiere estudios adicionales para identificar los factores que afectan a este desacuerdo

Lack of correlation between left ventricular outflow tract velocity time integral and stroke volume index in mechanically ventilated patients.

OBJECTIVE: To assess the correlation between left ventricular outflow tract velocity time integral (LVOT VTI) and stroke volume index (SVI) calculated by thermodilution methods in ventilated critically ill patients. DESIGN: A prospective, descriptive, multicenter study was performed. SETTING: Five intensive care units from university hospitals. PATIENTS: Patients older than 17 years needing mechanical ventilation and invasive hemodynamic monitoring were included. INTERVENTIONS: LVOT VTI was measured by pulsatile Doppler echocardiography. Calculations of SVI were performed through a floating pulmonary artery catheter (PAC) or a Pulse index Contour Cardiac Output (PiCCO®) thermodilution methods. MAIN VARIABLES: The relation between LVOT VTI and SVI was tested by linear regression analysis. RESULTS: One hundred and fifty-six paired measurements were compared. Mean LVOT VTI was 20.83±4.86cm and mean SVI was 41.55±9.55mL/m2. Pearson correlation index for these variables was r=0.644, p<0.001; ICC was 0.52 (CI 95% 0.4-0.63). When maximum LVOT VTI was correlated with SVI, Pearson correlation index was r=0.62, p<0.001. Correlation worsened for extreme values, especially for those with higher LVOT VTI. CONCLUSIONS: LVOT VTI could be a complementary hemodynamic evaluation in selected patients, but does not eliminate the need for invasive monitoring at the present time. The weak correlation between LVOT VTI and invasive monitoring deserves additional assessment to identify the factors affecting this disagreement.

Continuous tissue glucose monitoring correlates with measurement of intermittent capillary glucose in patients with distributive shock / La monitorización continua de la glucosa de tejido se correlaciona con la medición de glucosa capilar intermitente en pacientes con shock distributivo

BACKGROUND: Intermittent glycemic measurements in patients admitted to the intensive care unit (ICU) can result in episodes of severe hypoglycemia or in a poor control of glycemia range. We designed a study to assess accuracy and reliability of continuous monitoring of tissue glucose for patients with distributive shock. METHODS: Consecutive patients admitted to the ICU with a diagnosis of distributive shock and the need of insulin infusion for glycemic control were included in the study. These patients were implanted a Continuous Glucose Control Monitoring System (CGMS) with the sensor inserted subcutaneously into the abdominal wall. CGMS values were recorded every 5min. Capillary glucose (CG) was monitored for adjusting insulin perfusion according to the ICU protocol. Correlation between both methods was assessed. RESULTS: A total of 11,673 CGMS and 348 CG values were recorded. In five patients, CGMS failed to detect tissue glucose. A glucose value < 3.33 mmol/l (< 60 mg/dl) was observed in 3.6% of CGMS and in 0.29% CG values. 295 pairs of measurements were included in the statistical analysis for correlation assessment. The intraclass correlation coefficient was 0.706. The Pearson correlation coefficient was 0.71 (p < 0.0001, 95% CI 0.65-0.76). The mean of differences between both measurement methods was 0.22 mmol/l (3.98 mg/dl) (95% CI 0.66-7.31). CONCLUSIONS: When the Continuous Glucose Control Monitoring System (CGMS) is able to obtain data (75% of the patients), there is correlation between the values obtained by this method and capillary blood glucose in patients with distributive shock. CGMS can detect more episodes of glycemic excursions outside the normal range than intermittent capillary glucose monitoring. Variables that may impair glucose metabolism and peripheral soft tissues perfusion could impair CGMS measurements

ANTECEDENTES: la medición de glucemia intermitente pueden provocar episodios de hipoglucemia severa o un mal control glucémico en los pacientes ingresados en la Unidad de Cuidados Intensivos (UCI). Diseñamos un estudio para evaluar la exactitud y fiabilidad de la monitorización continua de glucosa tisular en pacientes con shock distributivo. MÉTODOS: Se incluyeron en el estudio todos los pacientes ingresados consecutivamente en la UCI con el diagnóstico de shock distributivo y la necesidad de insulina en perfusión para el control glucémico. A estos pacientes se les implantó un Sistema de Monitorización Continua de la Glucosa Tisular (CGMS) con un sensor insertado en tejido subcutáneo de la pared abdominal. CGMS valores se registraron cada cinco minutos. La glucosa capilar (GC) fue monitorizada para ajustar la perfusión de insulina de acuerdo con el protocolo de la UCI. Se evaluó la correlación entre ambos métodos. RESULTADOS: Se registraron un total de 11.673 valores de CGMS y 348 valores de CG. En cinco pacientes, la CGMS no pudo ser detectada. Un valor de glucosa < 3,33 mmol/l (< 60 mg/dl) se observó en 3,6% de los valores de CGMS y en el 0,29% de los valores de CG. 295 pares de mediciones se incluyeron en el análisis estadístico para la evaluación de la correlación. El coeficiente de correlación intraclase fue de 0,706. El coeficiente de correlación de Pearson fue de 0,71 (p < 0,0001; IC 95% 0,65-0,76). La media de las diferencias entre los dos métodos de medición fue de 0,22 mmol/l (3,98 mg/dl) (IC 95% 0,66 a 7,31). CONCLUSIONES: Cuando el sensor de medición de glucosa tisular continua es capaz de obtener datos (75% de los pacientes), existe correlación entre los valores obtenidos mediante este método y la glucemia capilar en los pacientes que presentan shock distributivo. CGMS puede detectar más episodios de excursiones glucémicas fuera del rango de normalidad que la monitorización intermitente de glucosa capilar. Variables que pueden perjudicar el metabolismo de la glucosa y la perfusión periférica de los tejidos blandos podrían afectar las mediciones CGMS

Continuous tissue glucose monitoring correlates with measurement of intermittent capillary glucose in patients with distributive shock.

BACKGROUND: Intermittent glycemic measurements in patients admitted to the intensive care unit (ICU) can result in episodes of severe hypoglycemia or in a poor control of glycemia range. We designed a study to assess accuracy and reliability of continuous monitoring of tissue glucose for patients with distributive shock. METHODS: Consecutive patients admitted to the ICU with a diagnosis of distributive shock and the need of insulin infusion for glycemic control were included in the study. These patients were implanted a Continuous Glucose Control Monitoring System (CGMS) with the sensor inserted subcutaneously into the abdominal wall. CGMS values were recorded every 5min. Capillary glucose (CG) was monitored for adjusting insulin perfusion according to the ICU protocol. Correlation between both methods was assessed. RESULTS: A total of 11,673 CGMS and 348 CG values were recorded. In five patients, CGMS failed to detect tissue glucose. A glucose value <3.33mmol/l (<60mg/dl) was observed in 3.6% of CGMS and in 0.29% CG values. 295 pairs of measurements were included in the statistical analysis for correlation assessment. The intraclass correlation coefficient was 0.706. The Pearson correlation coefficient was 0.71 (p<0.0001, 95% CI 0.65-0.76). The mean of differences between both measurement methods was 0.22mmol/l (3.98mg/dl) (95% CI 0.66-7.31). CONCLUSIONS: When the Continuous Glucose Control Monitoring System (CGMS) is able to obtain data (75% of the patients), there is correlation between the values obtained by this method and capillary blood glucose in patients with distributive shock. CGMS can detect more episodes of glycemic excursions outside the normal range than intermittent capillary glucose monitoring. Variables that may impair glucose metabolism and peripheral soft tissues perfusion could impair CGMS measurements.

[Characteristics of deep sedation in gastrointestinal endoscopic procedures performed by intensivists]. / Características de la sedación profunda en procesos endoscópicos gastrointestinales, realizada por médicos intensivistas.

OBJECTIVE: To determine tolerance, pain intensity, percentage of tests completed successfully and complications of deep sedation controlled by intensivists during gastrointestinal endoscopic procedures. DESIGN: A one-year, prospective observational study was carried out. SETTING: Department of Intensive Care intervention in the Endoscopy Unit of Hospital Universitario del Tajo (Spain). PATIENTS: Subjects over 15 years of age subjected to endoscopic procedures under deep sedation. RESULTS: A total of 868 patients were sedated during the study period, with the conduction of 1010 endoscopic procedures. The degree of tolerance was considered adequate («Very good¼/«Good¼) in 96.9% of the patients (95%CI: 95.7-98.1%), with a median score of 0 on the pain visual analog scale. A total of 988 endoscopic procedures were successfully completed (97.8%; 95%CI: 96.9-98.8%): 675 colonoscopies (97.1%) and 305 endoscopies (99.7%). Complications were recorded in 106 patients (12.2%; 95%CI: 10.0-14.5%). The most frequent being desaturation (6.1%), rhythm disturbances (5.1%) and hypotension (2.4%). CONCLUSION: Gastrointestinal endoscopic procedures under sedation controlled by intensivists are well tolerated and satisfactory for the patient, and are successfully completed in a very large percentage of cases. The procedures are associated with frequent minor complications that are resolved successfully.

Características de la sedación profunda en procesos endoscópicos gastrointestinales, realizada por médicos intensivistas / Characteristics of deep sedation in gastrointestinal endoscopic procedures performed by intensivists

OBJETIVO: Conocer la tolerancia, la intensidad del dolor, el porcentaje de pruebas completadas con éxito y las complicaciones de la sedación profunda, controlada por médicos intensivistas, para realizar procedimientos endoscópicos gastrointestinales. DISEÑO: Estudio observacional prospectivo durante un periodo de un año. Ámbito: Realizado por el Servicio de Medicina Intensiva en la Unidad de Endoscopias del Hospital Universitario del Tajo. PACIENTES: Mayores de 15 años a los que se realizó algún procedimiento endoscópico bajo sedación profunda. RESULTADOS: Durante el periodo de estudio fueron sedados 868 pacientes. Se les realizaron 1.010 procedimientos endoscópicos. El grado de tolerancia se consideró adecuado («Muy Bueno»/«Bueno») en el 96,9% (IC 95%: 95,7-98,1%) de los pacientes, con una mediana de dolor de 0 en la escala visual analógica. Un total de 988 procedimientos endoscópicos (97,8%; IC 95%: 96,9-98,8%) fueron completados con éxito, 675 colonoscopias (97,1%) y 305 gastroscopias (99,7%). Presentaron complicaciones 106 pacientes (12,2%; IC 95%: 10,0-14,5%). Las más frecuentes fueron la desaturación (6,1%), las alteraciones del ritmo (5,1%) y la hipotensión (2,4%). CONCLUSIÓN: La realización de procesos endoscópicos gastrointestinales bajo sedación profunda controlada por médicos intensivistas es bien tolerada, satisfactoria para el paciente y con un excelente porcentaje de pruebas completadas. Esta intervención se acompaña de frecuentes complicaciones, siendo todas de orden menor y resueltas con éxito

OBJECTIVE: To determine tolerance, pain intensity, percentage of tests completed successfully and complications of deep sedation controlled by intensivists during gastrointestinal endoscopic procedures. DESIGN: A one-year, prospective observational study was carried out. SETTING: Department of Intensive Care intervention in the Endoscopy Unit of Hospital Universitario del Tajo (Spain). PATIENTS: Subjects over 15 years of age subjected to endoscopic procedures under deep sedation. RESULTS: A total of 868 patients were sedated during the study period, with the conduction of 1010 endoscopic procedures. The degree of tolerance was considered adequate («Very good»/«Good») in 96.9% of the patients (95% CI: 95.7-98.1%), with a median score of 0 on the pain visual analog scale. A total of 988 endoscopic procedures were successfully completed (97.8%; 95% CI: 96.9-98.8%): 675 colonoscopies (97.1%) and 305 endoscopies (99.7%). Complications were recorded in 106 patients (12.2%; 95% CI: 10.0-14.5%). The most frequent being desaturation (6.1%), rhythm disturbances (5.1%) and hypotension (2.4%). CONCLUSION: Gastrointestinal endoscopic procedures under sedation controlled by intensivists are well tolerated and satisfactory for the patient, and are successfully completed in a very large percentage of cases. The procedures are associated with frequent minor complications that are resolved successfully

A new thoracic interfascial plane block as anesthesia for difficult weaning due to ribcage pain in critically ill patients / Nuevo bloqueo del plano interfascial torácico como anestesia para retiradas dificultosas de ventilación mecánica a causa de dolor torácico, en pacientes críticos

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Stability and specificity of heterodimer formation for the coiled-coil neck regions of the motor proteins Kif3A and Kif3B: the role of unstructured oppositely charged regions.

We investigated the folding, stability, and specificity of dimerization of the neck regions of the kinesin-like proteins Kif3A (residues 356-416) and Kif3B (residues 351-411). We showed that the complementary charged regions found in the hinge regions (which directly follow the neck regions) of these proteins do not adopt any secondary structure in solution. We then explored the ability of the complementary charged regions to specify heterodimer formation for the neck region coiled-coils found in Kif3A and Kif3B. Redox experiments demonstrated that oppositely charged regions specified the formation of a heterodimeric coiled-coil. Denaturation studies with urea demonstrated that the negatively charged region of Kif3A dramatically destabilized its neck coiled-coil (urea1/2 value of 3.9 m compared with 6.7 m for the coiled-coil alone). By comparison, the placement of a positively charged region C-terminal to the neck coiled-coil of Kif3B had little effect on stability (urea1/2 value of 8.2 m compared with 8.8 m for the coiled-coil alone). The pairing of complementary charged regions leads to specific heterodimer formation where the stability of the heterodimeric neck coiled-coil with charged regions had similar stability (urea1/2 value of 7.8 m) to the most stable homodimer (Kif3B) with charged regions (urea1/2 value of 8.0 m) and dramatically more stable than the Kif3A homodimer with charged regions (urea1/2, value of 3.9 m). The heterodimeric coiled-coil with charged extensions has essentially the same stability as the heterodimeric coiled-coil on its own (urea1/2 values of 7.8 and 8.1 m, respectively) suggesting that specificity of heterodimerization is driven by non-specific attraction of the oppositely unstructured charged regions without affecting stability of the heterodimeric coiled-coil.

Epidemiology of classic Kaposi's sarcoma in the Israeli Jewish population between 1960 and 1998.

Trends in the incidence of classic Kaposi's sarcoma in the Jewish population in Israel for the period between 1960 and 1998 were analysed. World standardised incidence rates of 20.7 and 7.5 per million among men and women, respectively, were calculated. The highest incidence rates were displayed by men originated from Africa and by Asian-born women.

Ki67 antigen and PCNA proliferation markers predict survival in anorectal malignant melanoma.

AIMS: To find a possible correlation of Ki67 antigen and proliferating cell nuclear antigen (PCNA) with prognosis in anorectal malignant melanoma. METHODS AND RESULTS: Thirty patients with anorectal malignant melanoma were studied. The percentage of tumour cells stained for Ki67 and PCNA in paraffin sections was assessed. Mode of treatment (local excision or abdominoperineal resection), depth of tumour invasion, attempt at cure as defined by complete tumour excision and absence of distant metastases at presentation, tumour blood vessel invasion, and tumour necrosis, as well as Ki67 and PCNA, were all correlated with survival. By univariate analysis, PCNA, Ki67, attempt at cure, local excision (and not abdominoperineal resection), and depth of invasion were all significantly associated with longer survival. By multivariate analysis, only PCNA was significantly associated with survival, while Ki67 showed a significant positive correlation with PCNA. With a cut-off point of 40%, patients with lower Ki67 scores showed survival advantage over those with higher Ki67 scores (P=0.0004). With a cut-off point of 80%, patients with lower PCNA scores showed survival advantage over those with higher PCNA scores (P=0.0001). The staining for proliferation markers was also associated with depth of tumour invasion. CONCLUSIONS: Ki67 and PCNA immunostaining in paraffin sections may be useful for the prediction of survival in patients with anorectal malignant melanoma. Larger studies are needed to confirm our results.

Structural cassette mutagenesis in a de novo designed protein: proof of a novel concept for examining protein folding and stability.

The solution to the protein folding problem lies in defining the relative energetic contributions of short-range and long-range interactions. In other words, the tendency of a stretch of amino acids to adopt a final secondary structural fold is context dependent. Our approach to this problem is to address whether an amino acid sequence, a "cassette," with a defined secondary structure in the three-dimensional structure of a native protein, can adopt a different conformation when placed into a different protein environment. Thus, we designed de novo a disulfide-bridged two-stranded alpha-helical parallel coiled coil, where each polypeptide chain consisted of 39 residues, as a "cassette holder." The 11-residue cassette would be inserted into the center of each polypeptide chain between the two nucleating alpha-helices to replace the control sequence. This Structural Cassette Mutagenesis model permits the analysis of short-range interactions within the inserted cassette as well as long-range interactions between the nucleating helices and the cassette region. The cassette holder, with a control sequence as the cassette, had a GdnHCl transition midpoint during denaturation of 5.6M. To demonstrate the feasibility of our model, an 11-residue beta-strand cassette from an immunoglobulin fold was inserted. The cassette was fully induced into the alpha-helical conformation with a [GdnHCl]1/2 value of 3.2M. To demonstrate the importance of short-range interactions (beta-sheet/alpha-helical propensities of amino acid side chains) in modulating structure and stability, a series of 1-5 threonine residues (highest beta-sheet propensity) were substituted into the solvent-exposed portions of the cassette in the alpha-helical conformation. Each successive substitution systematically decreased the stability of the coiled coil with peptide T4b (4 Thr residues) having a [GdnHCl]1/2 value of 2.2M. The single substitution of Ile in the hydrophobic core of the cassette with Ala or Thr had the most dramatic effect on protein stability (peptide 120T, [GdnHCl]1/2 value of 1.4M). Though these substitutions were able to modulate stability, they were not able to disrupt the alpha-helical conformation of the cassette, showing the importance of the nucleating alpha-helices on either side of the cassette in controlling conformation of the cassette. We have demonstrated the feasibility of our model protein to accept a beta-strand cassette. The effect of cassettes containing other beta-strands, beta-turns, loops, regions of undefined structure, and helical segments on conformation and stability of our model protein will also be determined.