Factors Associated With Healthcare Clinician Stress and Resilience: A Scoping Review.

GOAL: Clinician stress and resilience have been the subjects of significant research and interest in the past several decades. We aimed to understand the factors that contribute to clinician stress and resilience in order to appropriately guide potential interventions. METHODS: We conducted a scoping review (n = 42) of published reviews of research on clinician distress and resilience using the methodology of Peters and colleagues (2020). Our team examined these reviews using the National Academy of Medicine's framework for clinician well-being and resilience. PRINCIPAL FINDINGS: We found that organizational factors, learning/practice environment, and healthcare responsibilities were three of the top four factors identified in the reviews as contributing to clinician distress. Learning/practice environment and organizational factors were two of the top four factors identified in the reviews as contributing to their resilience. PRACTICAL APPLICATIONS: Clinicians continue to face numerous external challenges that complicate their work. Further research, practice, and policy changes are indicated to improve practice environments for healthcare clinicians. Healthcare leaders need to promote resources for organizational and system-level changes to improve clinician well-being.

Xq-Yq interchange resulting in supernormal X-linked gene expression in severely retarded males with 46,XYq- karyotype.

The critical importance of dosage compensation is underscored by a novel human syndrome ("XYXq syndrome") in which we have detected partial X disomy, demonstrated supernormal gene expression resulting from the absence of X inactivation, and correlated this overexpression with its phenotypic consequences. Studies of three unrelated boys with 46,XYq- karyotypes and anomalous phenotypes (severe mental retardation, generalized hypotonia and microcephaly) show the presence of a small portion of distal Xq on the long arm of the Y derivative. Cells from these boys exhibit twice-normal activity of glucose-6-phosphate dehydrogenase, a representative Xq28 gene product. In all three cases, the presence of Xq DNA on a truncated Y chromosome resulted from an aberrant Xq-Yq interchange occurring in the father's germline.

A systematic review and meta-analysis of the effects of community use of oral nutritional supplements on clinical outcomes.

The impact of oral nutritional supplements (ONS) on patients with complications (disease related morbidity) requires further exploration. This systematic review included 44 randomised controlled trials (RCT) (29 RCT surgical, 15 RCT medical patients) examining the effect of ONS in community settings on the incidence of complications (n = 716, mean age 67 years, range 35-87). ONS (mean intake 588 kcal/day, range 125-1750; protein 22 g/day, range 0-54; mean energy from protein 22 %, range 0-54) were prescribed for a mean 74 days, range 5-365. Most RCT (77 %) reported fewer complications in the ONS group versus control. Meta-analysis (39 RCT) showed ONS consumption reduced complications including infections, pressure ulcers, wound and fracture healing (OR 0.68, 95 % CI 0.59,0.79; p<0.001). Results showed reductions when ONS were used in hospital and community settings (OR 0.72, 95 % CI 0.59,0.87; p = 0.001) or just in the community (OR 0.65, 95 % CI 0.52, 0.80; p<0.001). Reductions in complications were only seen with high ONS adherence ≥ 80 % (OR 0.63, 95 % CI 0.48,0.83; p = 0.001) and ready-to-drink ONS (OR 0.69, 95 % CI 0.60,0.81; p<0.001). This systematic review and meta-analysis show community-based use of ONS in addition to the diet substantially reduces the incidence of complications. The diversity of ONS, patient populations and complication outcomes within the trials included in this review mean further research is warranted.

Providing spiritual care to cancer patients in the outpatient context: a pilot study.

The aim of this pilot study was to test an effort to provide spiritual care (SC) to oncology outpatients in the Ascension healthcare system. Medical providers referred patients who would benefit from spiritual and emotional support. Twenty-seven cancer outpatients from 5 states were enrolled in the project. Based on the chaplain assessment, 45% of the patients had moderate or severe spiritual concerns. On average patients had 4 sessions with a chaplain (range 2-9). Of the 136 chaplain sessions, 56% were in-person in the clinic and 35% were by phone. The most common chaplain activities were active listening (87% of the sessions) and demonstrate caring and concern (55%). For the 20 patients who provided follow-up data, there were decreases in all measures of religious/spiritual distress, though statistically insignificant, and a marginally significant increase (p < .054) in well-being. The study adds to the emerging literature that describes the importance of SC in the outpatient context.

Effect of oral nutritional supplements on outcomes in children presenting with, or at risk of, faltering growth in clinical settings: A systematic review and meta-analysis.

This systematic review summarises evidence regarding oral nutritional supplement (ONS) use in children with, or at risk of, faltering growth (FG). Ten randomised controlled trials (RCTs), compared changes in outcomes amongst children receiving ONS versus control were included. Overall, 1116 children (weighted mean (WM) age 5 years; n658 (59%) male) were recruited, of which 585 (52%) received ONS (WM intake contribution 412 kcal, 16.3 g protein, 395 ml) for 116 days (WM). ONS use was associated with significantly greater gains in weight (mean difference (MD) 0.4 kg, 95% CI [0.36, 0.44]) and height (MD 0.3 cm, 95% CI [0.03, 0.57]), likely related to improvements in nutritional intake. Mean compliance to prescribed dose was 98%. Data suggested an association between ONS use and reduced infections. Further research is warranted to establish ONS dosage and effects upon other outcomes. This review provides evidence to support use of ONS in the management of children with, or at risk of, FG.

Economic Impact of Implementing Malnutrition Screening and Nutritional Management in Older Adults in General Practice.

OBJECTIVES: Malnutrition is a common and significant public health problem, especially for older adults, as the consequences are costly. National guidelines (NICE CG32/QS24) highlight the need to identify and manage malnutrition, the implementation of which was deemed "high impact to produce cost savings". The 'Malnutrition Pathway', endorsed by NICE and other professional bodies, is a practical evidence-based guide to help community healthcare professionals (HCP) to implement guidance on malnutrition management. Published evaluations of its use are needed. DESIGN: This service evaluation in older adults assessed the impact of implementing the 'Malnutrition Pathway' on health care use and costs, as well as the acceptability of the management strategies and effect on malnutrition risk. SETTING: 5 GP surgeries in Gloucestershire. PARTICIPANTS: 163 older adults (80±9 years) with a range of primary diagnoses, living in their own home, were screened using the Malnutrition Universal Screening Tool ('MUST') (n50 low risk (LR); n41 medium risk (MR); n72 high risk (HR)). All patients were managed according to risk (LR: no further management; MR: dietary advice (DA); and HR: DA plus two oral nutritional supplements (ONS) (1 serve 300kcal, 18g protein; 125ml). MEASUREMENTS: At each review (6weeks, 3 and 6 months), 'MUST' score, compliance and satisfaction to their management plan were recorded. Healthcare use was collected from GP records 6 months before and after implementation of the pathway. A simple cost analysis was completed. RESULTS: Implementing appropriate management of malnutrition led to significant reductions in hospital admissions (p=0.028), length of hospital stay (p=0.05), GP visits (p=0.007) and antibiotic prescriptions (p=0.05). Over 6 months, the costs to manage malnutrition (HCP time, ONS) were more than offset by the savings associated with these reductions in health care use (per patient savings of -£395.64 MR+HR; -£997.02 HR). The proportion of individuals at risk of malnutrition reduced over time, and patients reported being satisfied with the DA (97%) and ONS (96%), consuming 90% of their ONS prescription. CONCLUSION: Managing malnutrition significantly reduces healthcare use, with a positive budget impact, in older malnourished patients in primary care. This represents an opportunity to improve patient care with benefit on health care spend.

Case of eosinophilic fasciitis during military training in a Nepalese British infantry soldier.

We present the case of a Nepalese British soldier with peripheral oedema and a significantly raised eosinophil count. After extensive investigation looking for a parasitic cause of his illness, he was diagnosed with eosinophilic fasciitis, a connective tissue disorder, often triggered by heavy exertion and responsiveness to immunosuppression. In a military setting, in which clinicians are likely to encounter patients who have spent time in tropical areas, it is important to still consider non-infectious causes of eosinophilia.

Proteomic analysis of scleroderma lesional skin reveals activated wound healing phenotype of epidermal cell layer.

OBJECTIVE: To identify using proteomic analysis, proteins of altered abundance in the skin of patients with SSc. METHODS: 4 mm excision biopsies were obtained from the forearm involved skin of 12 diffuse SSc patients and 12 healthy controls. Two-dimensional gel electrophoresis was used to separate and define proteins in normal and SSc skin biopsy material. Proteins of altered abundance in the disease were formally identified by mass spectroscopy. Abnormalities of the epidermis were confirmed by immunohistochemistry. RESULTS: Proteomic analysis revealed altered abundance of proteins involved in extracellular matrix production, myofibroblast contractility, energy metabolism and response to oxidative stress. In addition, proteins specific to the epidermis and involved in epidermal cell differentiation were altered in abundance in the disease. SSc epidermis is thickened, has an expanded nucleated cell layer, and exhibits abnormal persistence of basal marker keratin 14, delayed expression of maturation markers keratin 1/10 and the induction of keratins 6 and 16, normally absent from interfollicular skin and induced following epidermal injury. These changes closely resemble the activated phenotype seen during wound healing. CONCLUSIONS: Consistent with previous models of SSc pathogenesis these data are showing increased contractility, increased extracellular matrix and response to oxidative stress in the involved skin of recent onset SSc patients. In addition, we show that SSc epidermis has an activated, wound healing phenotype. These findings are important because epidermal cells activated by injury induce and regulate local fibroblasts during wound repair.

Community nurses' practices in managing perianal abscesses.

A survey of community nurses identified that a wide range of dressings, and in some cases unethical practices, are being used for this simple postoperative condition. Communication between hospital, community staff and patients was poor.

The influence of deprivation on malnutrition risk in outpatients with chronic obstructive pulmonary disease (COPD).

BACKGROUND & AIMS: The social gradient in chronic obstructive pulmonary disease (COPD) is considerable, but the influence of deprivation on common clinical risk factors such as malnutrition is unclear. This study aimed to explore the relationship between COPD disease-severity, deprivation and malnutrition. METHODS: 424 outpatients with a confirmed diagnosis of COPD were routinely screened for malnutrition risk using the 'Malnutrition Universal Screening Tool' ('MUST') while attending respiratory clinics across two hospitals; a large city hospital (site A) and a smaller community hospital (site B). Deprivation was assessed for each outpatient according to their address (postcode) using the English governments' index of multiple deprivation (IMD) and related to malnutrition risk. Each postcode was attributed to both an IMD score and IMD rank, where a higher IMD score and a lower IMD ranking indicated increased deprivation. RESULTS: Overall prevalence of malnutrition was 22% (95% CI 18-26%; 9% medium risk, 13% high risk). It was significantly higher at site A (28% vs 17%; p = 0.004) where patients were also significantly more likely to reside in areas of more deprivation than those at site B (IMD rank: 15,510 SD 8137 vs 22,877 SD 6827; p < 0.001). COPD disease-severity was positively associated with malnutrition (p < 0.001) whilst a higher rank IMD was negatively associated with malnutrition (p = 0.014). CONCLUSIONS: Deprivation is a significant independent risk factor for malnutrition in outpatients with COPD. Consideration of deprivation is important in the identification of malnutrition and the nutritional management of patients with COPD.

Iloprost suppresses connective tissue growth factor production in fibroblasts and in the skin of scleroderma patients.

Patients with scleroderma receiving Iloprost as a treatment for severe Raynaud's phenomenon report a reduction in skin tightness, suggesting that this drug inhibits skin fibrosis. Connective tissue growth factor (CTGF), a recently described profibrotic cytokine, acts downstream and in concert with TGF-beta to stimulate the fibrotic process and is involved in the fibrosis seen in scleroderma. Here we show that Iloprost, acting by elevation of cAMP, blocks the induction of CTGF and the increase in collagen synthesis in fibroblasts exposed to TGF-beta. The potency of Iloprost with respect to suppression of CTGF far exceeds that of other prostanoid receptor agonists, suggesting that its effect is mediated by the prostacyclin receptor IP. By sampling dermal interstitial fluid using a suction blister device, we show that CTGF levels are greatly elevated in the dermis of scleroderma patients compared with healthy controls and that Iloprost infusion causes a marked decrease in dermal CTGF levels. These studies suggest that Iloprost could be reducing the level of a key profibrotic cytokine in scleroderma patients and that endogenous production of eicosanoids may limit the fibrotic response to TGF-beta.

Scleroderma renal crisis: patient characteristics and long-term outcomes.

BACKGROUND: Scleroderma renal crisis (SRC) is an important complication of systemic sclerosis, causing acute renal failure, and usually hypertension. AIMS: To review the clinical and pathological features of SRC, and correlate them with renal outcomes and mortality. DESIGN: Retrospective case series. METHODS: We identified 110 cases of SRC managed at a single centre between 1990 and 2005. RESULTS: SRC occurred in 5% of scleroderma cases under follow-up. Cases were predominantly female (81%), with diffuse cutaneous disease (78%). RNA polymerase antibodies were found in 59% of cases tested. Almost all (108/110) received treatment with ACE inhibitors (ACEIs). Dialysis was not required in 36%, was required temporarily (for up to 3 years) in 23%, was required permanently in 41%. Patients not on dialysis showed improvement in estimated glomerular filtration rate after SRC (mean change +23 ml/min over 3 years). Poor renal outcome was associated with lower blood pressure at presentation, and with higher age in those requiring dialysis. Steroid use, microangiopathic haemolytic anaemia, and antibody profile were not related to renal outcome. In the 58 renal biopsies available for clinical correlation, acute changes of mucoid intimal thickening in arteries and fibrinoid necrosis in arterioles were associated with a poorer renal outcome. Mortality was high (59% survival at 5 years), and was higher in men. DISCUSSION: Despite the efficacy of ACEIs in managing SRC, the poor long-term outcome warrants evaluation for additional treatments for this devastating complication of systemic sclerosis.

Structure and localization of genes encoding aberrant and normal epidermal growth factor receptor RNAs from A431 human carcinoma cells.

A431 cells have an amplification of the epidermal growth factor (EGF) receptor gene, the cellular homolog of the v-erb B oncogene, and overproduce an aberrant 2.9-kilobase RNA that encodes a portion of the EGF receptor. A cDNA (pE15) for the aberrant RNA was cloned, sequenced, and used to analyze genomic DNA blots from A431 and normal cells. These data indicate that the aberrant RNA is created by a gene rearrangement within chromosome 7, resulting in a fusion of the 5' portion of the EGF receptor gene to an unidentified region of genomic DNA. The unidentified sequences are amplified to about the same degree (20- to 30-fold) as the EGF receptor sequences. In situ hybridization to chromosomes from normal cells and A431 cells show that both the EGF receptor gene and the unidentified DNA are localized to the p14-p12 region of chromosome 7. By using cDNA fragments to probe DNA blots from mouse-A431 somatic cell hybrids, the rearranged receptor gene was shown to be associated with translocation chromosome M4.

Enteral (oral or tube administration) nutritional support and eicosapentaenoic acid in patients with cancer: a systematic review.

The aim of this systematic review was to determine the efficacy and potential benefits of enteral nutritional support [oral nutritional supplements (ONS) or enteral tube feeding (ETF)], and eicosapentaenoic acid (EPA, free acid, ethyl esters or fish oil; provided as capsules or enriched ONS or ETF) in patients with cancer. Clinical studies were identified using electronic databases, and studies were selected according to predetermined criteria. For each treatment modality (chemo/radiotherapy, surgery, and palliative care), the comparisons of interest were nutritional support vs. routine care (no nutritional support), EPA supplement (capsule or enriched ONS or ETF) vs. routine care (no supplement or standard supplement), ETF vs. parenteral nutrition (PN). The reviewed outcomes were dietary intake, anthropometry, clinical (mortality, length of hospital stay, complications, and quality of life) and haematological/biochemical (white blood cell count, serum transferrin and albumin, CD3-positive lymphocytes, and inflammatory markers). Meta-analyses were performed where possible. In patients undergoing radiotherapy, meta-analysis showed that ONS significantly increase dietary intake (381 kcal/day, 95% CI 193 to 569 in 3 RCTs) compared to routine care. In patients undergoing surgery, meta-analyses showed that ETF results in a significantly shorter length of hospital stay (1.72 fewer days, 95% CI 0.90 to 2.54 in 8 RCTs), lower incidence of any complications (OR 0.62, 95% CI 0.50 to 0.77 in 4 RCTs) and infectious complications (OR 0.67, 95% CI 0.55 to 0.82 in 11 RCTs) and lower sepsis scores (2.21 points, 95% CI 1.49 to 2.92 in 2 RCTs), but no difference in mortality (OR 0.72, 95% CI 0.40 to 1.29 in 7 RCTs) compared to PN. There was also no difference in mortality between ONS or ETF vs. routine care in patients undergoing chemotherapy/radiotherapy (OR 1.00, 95% CI 0.62-1.61 in 4 RCTs) or surgery (OR 2.44, 95% CI 0.75 to 7.95 in 4 RCTs). Individual studies of EPA supplementation as capsules showed improvements in survival, complications and inflammatory markers in patients undergoing bone marrow transplant (BMT). In palliative care patients receiving EPA-enriched ONS or capsules, there were inconsistent positive effects on survival and quality of life. In those undergoing surgery, EPA-enriched ETF had no effect. Further research is required to elucidate the clinical efficacy of enteral nutrition support, including the potential benefits of EPA supplementation, in patients with cancer.

Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations.

The genetic aetiology of autism remains elusive. Occasionally, individuals with Cowden syndrome (a cancer syndrome) and other related hamartoma disorders such as Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Proteus-like conditions, are characterised by germline PTEN mutations, and may have neurobehavioural features resembling autism as well as overgrowth and macrocephaly. Therefore, we undertook PTEN gene mutation analysis in 18 subjects mainly prospectively ascertained with autism spectrum disorder and macrocephaly. Of these 18 autistic subjects (13 males and five females; ages 3.1-18.4 years) with a head circumference range from 2.5 to 8.0 standard deviations above the mean, three males (17%) carried germline PTEN mutations. These three probands had previously undescribed PTEN mutations: H93R (exon 4), D252G (exon 7), and F241S (exon 7). They had the larger head circumference measurements amongst all our study subjects. The three residues altered in our patients were highly evolutionarily conserved. We suggest that PTEN gene testing be considered for patients with autistic behaviour and extreme macrocephaly. The gene findings may impact on recurrence risks as well as medical management for the patient.

N-terminal connective tissue growth factor is a marker of the fibrotic phenotype in scleroderma.

BACKGROUND: Over-expression of connective tissue growth factor (CTGF) is a hallmark of fibrotic disease, including scleroderma. CTGF acts with the pro-fibrotic cytokine TGFbeta to promote sustained fibrotic responses in vivo. Elevated production of CTGF might be responsible for maintenance of the fibrotic phenotype in scleroderma. Assays of CTGF or of its fragments are potential non-invasive measures of the fibrotic response in scleroderma. AIM: To determine the utility of whole, N-terminal, and C-terminal CTGF as surrogate markers for fibrosis in scleroderma. DESIGN: Cross-sectional controlled study. METHODS: Plasma was collected prospectively from 47 scleroderma patients (26 diffuse scleroderma, 21 limited scleroderma) and 18 healthy controls. At the same time, dermal interstitial fluid was derived by a suction blister technique from the lesional skin of scleroderma patients, and from the forearm skin of healthy controls. Whole, N-terminal, and C-terminal CTGF were assayed by ELISA, using monoclonal antibodies specific for N- and C-terminal epitopes. RESULTS: N-terminal cleavage products of CTGF were present at elevated levels in the plasma and dermal interstitial fluid of scleroderma patients, compared to healthy controls. N-terminal CTGF levels in plasma and dermal interstitial fluid correlated with severity of skin disease and (negatively) with disease duration. Whole and C-terminal CTGF levels were low in blister fluid and plasma levels were not elevated in disease. DISCUSSION: These results support a role for CTGF in scleroderma-associated fibrosis and the utility of N-terminal CTGF as a marker of fibrosis.

To screen or not to screen for adult malnutrition?

BACKGROUND: There is some controversy about whether all adults receiving healthcare should be routinely screened for nutritional problems. METHODS: (i) A systematic review examined the proposition that malnutrition is under-recognised and under-treated, and that nutritional interventions in malnourished patients, identified through a screening procedure produce clinical benefits (assessed using randomised controlled trials, RCTs). (ii) A systematic review of nutritional screening interventions in populations of malnourished and well-nourished subjects (RCTs and non-RCTs). RESULTS: (i) The prevalence of malnutrition varies according to the criteria used, but is estimated to affect 10-60% of patients in hospital and nursing homes, 10% or more of older free-living subjects, and less than 5% of younger adults. In the absence of formal screening procedures, more than half the patients at risk of malnutrition in various settings do not appear to be recognised and/or are not referred for treatment. RCTs show that nutritional interventions in malnourished patients produce various clinical benefits. (ii) Interventions with nutritional screening in different care settings also generally suggest clinical benefits, but some are limited by small sample sizes and inadequate methodology. Factors that influence outcomes include validity, reliability and ease of using the screening procedure, the 'care gap' that exists between routine and desirable care and the need for other resources, which may increase or decrease following screening. CONCLUSIONS: The frequent failure to recognise and treat malnutrition, especially where it is common, is unacceptable. In such circumstances, the routine use of a simple screening procedure is recommended. Each health care setting should have a transparent policy about nutritional screening, which may vary according to the 'care gap', available resources, and specific populations of patients, in which the prevalence of malnutrition may vary widely.

Improved glycemic control after supervised 8-wk exercise program in insulin-dependent diabetic adolescents.

Eight insulin-dependent adolescents (4 boys, 4 girls) participated in an 8-wk program of supervised exercise, and 8 matched controls were encouraged to exercise on their own without supervision. All 16 subjects were asked to follow a standard ADA diet plan, kept a self-reported log of caloric intake, and met with a dietitian weekly to review their diets. Exercise for the supervised subjects was scheduled between the routine afternoon snack and the evening meal, and subjects were asked not to consume additional food on exercise days. After the 8-wk program, glycemic control, as measured by glycosylated serum albumin and blood glucose values (but not by glycosylated hemoglobin), improved in the supervised-exercise group despite reduced daily insulin dosage. Cardiorespiratory fitness, as measured by voluntary maximum treadmill time (Bruce protocol) and submaximal exercise heart rates, also improved. No changes were observed in the unsupervised control group.

Serum markers of oxidative stress and severity of diabetic retinopathy.

OBJECTIVE: To compare serum markers of oxidative stress with diabetic retinopathy severity RESEARCH DESIGN AND METHODS: This cross-sectional study compared patients with types 1 and 2 diabetes with control subjects in western New York and Pennsylvania. Retinopathy severity was graded from funduscopic fields based on the Early Treatment of Diabetic Retinopathy Study. Serum samples were analyzed for thiobarbituric acid-reacting substances (TBARS), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, creatinine, HbA1, and triglycerides. Appropriate analysis of covariance models were performed. RESULTS: TBARS (P = 0.019), triglyceride (P = 0.004), and glucose and HbA1 (both P<0.001) levels were elevated in diabetic patients compared with those in control subjects. SOD (P = 0.003) and GSH-Px (P = 0.046) levels were lower in diabetic patients than in control subjects. No correlation existed between SOD levels and either glucose or HbA1 levels. No significant associations existed between levels of TBARS, SOD, or GSH-Px and severity of diabetic retinopathy There was a significant association between poorer visual acuity and worse retinopathy (P = 0.009), which was only partly explained by macular edema. CONCLUSIONS: Increased levels of TBARS and decreased levels of SOD and GSH-Px were found in diabetic patients compared with those in control subjects, but no significant associations were found between the levels of these substances and severity of retinopathy When duration and type of diabetes and serum HbA1 levels were taken into account, only visual acuity remained associated with more severe retinopathy.

Nucleotide sequence of the gene coding for a 130-kDa mosquitocidal protein of Bacillus thuringiensis israelensis.

The nucleotide sequence of pVB131 containing the gene coding for a 130-kDa Bacillus thuringiensis israelensis (B.t.isr) mosquitocidal protein was determined. The pVB131 plasmid was constructed by Sekar and Carlton [Gene 33 (1985) 151-158]. Our sequencing revealed only one open reading frame large enough to code for a protein of 130 kDa. The translation start site was determined by sequencing the protein isolated from B.t.isr. The amino acid sequence of the protein was deduced from the nucleotide sequence, and its Mr was determined as 128,505. Immunological and biochemical analyses of B.t.isr mosquitocidal proteins indicated that the 130-kDa protein coded by pVB131 was indeed expressed in B.t.isr. Comparing the peptide sequence of the 130-kDa B.t.isr toxin with the sequences of other B.t. toxins having activities specific to lepidopteran species showed that several domains were highly homologous. This suggests that they are evolutionarily related to each other, and in the evolutionary process the sequences in the homologous domains that are important to the insecticidal activity have been conserved.