Carob seeds as a source of bioactive flavonoid derivatives: isolation, network pharmacology-guided anti-cancer activity, and HPLC standardization.

INTRODUCTION:  Carob, Ceratonia siliqua L. (CS), is a legume well-known for its edible pod pulp. Its seeds are used almost exclusively as a source of the food additive E410. Although a variety of metabolites have been identified by HPLC and LC-MS analysis in CS, reports concerned with their isolation are scarce.   Methodology: In this study, two flavonoid derivatives were isolated from the methanolic extract of CS seeds, namely, quercetin-3-O-rhamnoside and 4'-p-hydroxybenzoylisorhamnetin-3,7-di-O-rhamnoside. Network pharmacology was unusually used as a guide for estimation of the biological potential of the isolated compounds. Finally, the methanolic extract of CS seeds and its ethyl acetate fraction were standardized for their 4'-p-hydroxybenzoylisorhamnetin-3,7-di-O-rhamnoside content by HPLC. RESULTS:  The identified isolates displayed the ability to interfere with the activity of several target proteins associated with renal and colon cancers. Their cytotoxic effect on renal and colorectal cancer cell lines was investigated in comparison to Doxorubicin. The selectivity of the isolated compounds was evaluated on normal human fetal fibroblast cell lines. The isolated 4'-p-hydroxybenzoylisorhamnetin-3,7-di-O-rhamnoside showed very potent cytotoxic activity against the tested cell lines with the highest selectivity. CONCLUSION:  CS seeds can be used as a source of bioactive flavonoid derivatives that can be incorporated in pharmaceutical industries.

Thermal, mechanical, and electrical properties of Si-stacked nanosheet transistors using machine learning interatomic potentials.

Thermal and mechanical properties play a key role in optimizing the performance of nanoelectronic devices. In this study, the lattice thermal conductivity (κL) and elastic constants of Si nanosheets at different sheet thicknesses were determined using recently developed machine learning interatomic potentials (MLIPs). A Si nanosheet with a minimum thickness of 10 atomic layers was used for model training to predict the properties of sheets with greater thicknesses. The training dataset was efficiently constructed using stochastic sampling of the potential energy surface (PES). Density functional theory (DFT) calculations were used to extract the MLIP, which served as the basis for further analysis. The Moment Tensor Potential (MTP) method was used to obtain the MLIP in this study. The results showed that, at sub-6 nm sheet thickness, the thermal conductivity dropped to ∼ 7 % of its bulk value, whereas some stiffness tensor components dropped to ∼ 3 % of the bulk values. These findings contribute to the understanding of heat transport and mechanical behavior of ultrathin Si nanosheets, which is crucial for designing and optimizing nanoelectronic devices. The technological implications of the extracted parameters on nanosheet field-effect transistor (NS-FET) performance at advanced technology nodes were evaluated using TCAD device simulations.

Draft genomes of 10 Vibrio cholerae isolates collected in Sudan in 2019.

This report presents the first genomes from positive cases of cholera in Sudan. Genomic analysis of 10 Vibrio cholerae isolates, profiled as serogroup O1, reveals evidence of antimicrobial resistance genes and a 139-kb IncC plasmid with 99.74% identity to the multidrug-resistant plasmid pCNRVC190243 previously reported in Yemen and Lebanon.

Improving Blood Transfusion Request Form Documentation: A Quality Improvement Project.

BACKGROUND: The transfusion quality improvement project (QIP) serves as a valuable tool for assessing and educating individuals who request blood components. The World Health Organization (WHO) recommends that each institution utilize a blood transfusion request form to ensure the effective conveyance of patient information to the hospital's blood bank. This QIP aimed to implement a transfusion request form and measure compliance with its use. METHODS: A prospective study was conducted at Al Managil Teaching Hospital, Sudan, from May 1 to August 3, 2024, to address the lack of standardized transfusion request forms. The study included three cycles involving pre-intervention analysis, two phases of intervention with training sessions, and post-intervention evaluations. The interventions focused on developing and implementing a new transfusion request form, training clinical physicians, and reinforcing the form's use. Data from 100 randomly selected transfusion request forms were analyzed for completeness and adherence. RESULTS: The study showed significant improvements in the completeness of transfusion request forms across three cycles. In the first cycle, no data were collected, highlighting the absence of standardized forms. During the second cycle, with the introduction of the new form, the completion rates varied: some fields, such as patient information and clinical details, were fully completed in 50 cases (100%), while critical clinical parameters, such as current hemoglobin (Hb) and platelet (PLT) levels, were completed in only four requests (8%). By the third cycle, there was a substantial increase in completion rates across all domains. For example, patient information fields achieved 100% completion in 50 cases, and clinical parameters saw significant improvement, with current Hb and PLT levels documented in 48 cases (96%). The mean percentage completion increased from 68.1% in the second cycle to 97.9% in the third cycle, demonstrating the effectiveness of the interventions and training sessions. Minor decreases were observed in health insurance documentation and certain clinical details, indicating areas for further improvement. CONCLUSION: The systematic implementation and iterative evaluation of transfusion request forms significantly enhanced documentation completeness.

Functional Outcomes of a Dynamic Condylar Screw for Unstable Femoral Intertrochanteric Fractures in Patients Above 50.

BACKGROUND: Hip fractures are among the most common fractures encountered in the emergency departments by orthopedic trauma teams. The optimal treatment method and implant choice for unstable intertrochanteric fractures are subject to debate, with various options available, including intramedullary and extramedullary implants. METHODS: In this descriptive cross-sectional study, the researchers examined patients with unstable intertrochanteric fractures (classified as 31A2 according to the AO Foundation/Orthopaedic Trauma Association (AO/OTA) classification) who had undergone open reduction and internal fixation with a 95° dynamic condylar screw (DCS). The study was conducted at the Gezira Centre for Orthopedic Surgery and Traumatology (GCOST) during the latter half of 2022. Functional outcomes were assessed using the modified Harris Hip Score (mHHS). RESULTS: A total of 30 patients were enrolled in this study, with a mean age of 73 ± 12.27 years. Of these, 11 (36.7%) were male, and 19 (63.3%) were female. The mHHS was 73.6 ± 14.654. Among the surveyed patients, seven (23.3%) reported poor outcomes, 13 (43.3%) reported fair outcomes, six (20%) reported good outcomes, and four (13.3%) reported excellent outcomes. The Kruskal-Wallis test revealed statistically differences in mean mHHS scores between gender groups (p = 0.024) and between age groups (p = 0.04). However, no significant differences were found across different modes of trauma groups (p = 0.73), affected hip groups (p = 0.35), comorbidity groups (p = 0.84), or postoperative complication groups (p = 0.06). CONCLUSION: Our study found that DCS treatment for unstable intertrochanteric fractures yielded acceptable functional outcomes, making it a viable and effective treatment option.

Bat Ear Correction Steps and Outcomes for Better Life Support.

An unusually projecting human ear is known as a prominent ear, otapostasis, or bat ear. It might be both bilateral and unilateral. The scapha and antihelix of the big concha are not well formed. It is the outcome of cartilage deformity that occurred during early ear development in utero. After the child reaches five years old, the abnormality can be corrected at any time. In order to prevent psychological suffering, the procedure should ideally be performed as soon as possible. Otoplasty correction is reshaping the ear cartilage to bring the ear closer to the side of the head. The cartilage is reshaped, but the skin is left in place. Hearing remains unaffected by the operation. It is mainly done for aesthetic reasons. Although they are uncommon, the post-operative consequences from the operation include hematoma development, keloid formation, infection, and asymmetry in the ears. Otoplasty is a cosmetic operation that involves permanent sutures to alter the size, shape, or location of the ear. The main purpose of otoplasty is to treat promin auris, or bulging ears. Promin auris, the principal indication for otoplasty, is the subject of this review. The indications, contraindications, and method utilized in otoplasty are reviewed in this exercise, which also emphasizes the need of pre- and post-operative care for patients having this surgery. Otoplasty results are generally lifelong and will improve the self-confidence. The goals of otoplasties are to make the ears appear more natural in comparison to the head and help with the overall contour of the ears. Final ear surgery results will be visible after a two week recovery period, with small improvements appearing for up to 12 months post-procedure. A proper understanding of the diagnosis, indications, and surgical techniques will lead to positive outcomes in otoplasty.

A Study at Wad Madani, Sudan: Are We Documenting Acute Ankle Fractures Effectively?

BACKGROUND: Medical records are essential documents that outline a patient's medical history and current health status. It involves maintaining records that include assessments of patient outcomes, care plans, and interventions necessary to meet patient needs. A patient's medical record encompasses details about their condition, as documented by healthcare professionals, including clinical assessments, evaluations, and professional opinions related to the delivery of care. METHODS:  This retrospective study aimed to evaluate the adequacy of our documentation for acute ankle fractures in accordance with the British Orthopaedic Association Standards for Trauma and Orthopaedics (BOAST) guidelines, encompassing a total of 41 cases. The research was conducted at the Gezira Center for Orthopedic Surgery and Traumatology (GCOST) in Wad Madani, Sudan, from May 12 to July 12, 2022. RESULTS: Of the 41 recorded notes for acute ankle fractures, 26 (63.4%) were documented by medical officers and 15 (36.6%) by orthopaedic trainees. Most fractures (25 cases, 61%) occurred in individuals aged 18-40 years, and the gender distribution showed that males accounted for most fractures, with 29 cases (70.7%). Additionally, all patients (100%) had a documented cause of injury. Skin integrity was noted in 38 patients (92.7%). Vascular examination was documented in 18 patients (43.9%), while neurological examination was recorded in 16 patients (39%). CONCLUSION: Although the cause of ankle fractures was reported in all patients, the neurovascular examination was insufficiently documented, compromising patient care and failing to meet national standards, as highlighted in our study. We recommend implementing the BOAST guidelines to ensure proper documentation and essential assessments.

Beyond Conventional Imaging: A Systematic Review and Meta-Analysis Assessing the Impact of Computed Tomography Perfusion on Ischemic Stroke Outcomes in the Late-Window.

BACKGROUND: Non-contrast CT (NCCT) and CT angiogram (CTA) have become essential for endovascular treatment (EVT) in acute stroke. Patient selection may improve when CT perfusion imaging (CTP) is also added for patient selection. We aimed to analyze the effects of implementing CTP in acute ischemic stroke (AIS) patients' treatment to assess whether stroke outcomes differ in the late window. METHODS: We searched the PubMed, Embase, and Web of Sciences databases to obtain articles related to CTA and CTP in EVT. Collected patient data was split into two groups: the CTP and control (NCCT+CTA) cohorts. Primary outcomes evaluated were modified Rankin Scale (mRS) scores, symptomatic intracranial hemorrhages (sICH), mortality, and successful recanalization. RESULTS: There were 14 studies with 5,809 total patients in the final analysis: 2,602 received CTP and 3,202 were in the control group. CTP/CTA patients showed significantly lower rates of 90-day stroke-related mortality (OR: 0.72, 95% CI 0.60-0.87, p<0.01) and significantly higher successful recanalization (OR: 1.42, 95% CI 1.06-1.94, p<0.01) compared to CTA-only patients. Analysis of other outcomes including functional independence (mRS 0-2), critical times, and intracranial hemorrhages were non-significant (p > 0.05). CONCLUSION: The study highlights the usefulness of CTP-guided therapy as a supplementary tool in EVT selection in the late window. Although the addition of CTP resulted in lower mortality, the favorable outcomes did not improve. Further evidence is required to establish a clearer understanding of the potential advantages or limitations of incorporating CTP in stroke imaging.

Assessing the effectiveness of greater occipital nerve block in chronic migraine: a systematic review and meta-analysis.

BACKGROUND & AIMS: Chronic migraine poses a global health burden, particularly affecting young women, and has substantial societal implications. This study aimed to assess the efficacy of Greater Occipital Nerve Block (GONB) in individuals with chronic migraine, focusing on the impact of local anesthetics compared with placebo. METHODS: A meta-analysis and systematic review were conducted following the PRISMA principles and Cochrane Collaboration methods. Eligible studies included case-control, cohort, and randomized control trials in adults with chronic migraine, adhering to the International Classification of Headache Disorders, third edition (ICHD3). Primary efficacy outcomes included headache frequency, duration, and intensity along with safety assessments. RESULTS: Literature searches across multiple databases yielded eight studies for qualitative analysis, with five included in the final quantitative analysis. A remarkable reduction in headache intensity and frequency during the first and second months of treatment with GONB using local anesthetics compared to placebo has been reported. The incidence of adverse events did not differ significantly between the intervention and placebo groups. CONCLUSION: The analysis emphasized the safety and efficacy of GONB, albeit with a cautious interpretation due to the limited number of studies and relatively small sample size. This study advocates for further research exploring various drugs, frequencies, and treatment plans to enhance the robustness and applicability of GONB for chronic migraine management.

Rare occurrence of sagittal sinus thrombosis and haemorrhagic infarction with dengue fever: jumping from traditional symptoms to lethal neurological consequences.

Introduction and importance: Dengue virus (DENV) is an RNA virus transmitted by Aides mosquito causing dengue fever. There is growing recognition of neurological symptoms associated with DENV infection, some of which might be lethal if left untreated. Case reports describing sagittal sinus thrombosis, as a serious neurologic consequence of dengue infection, are rare. It is still unknown how often sagittal sinus thrombosis occurs and what variables increase the risk in dengue patients. Case presentation: Herein the authors presented an elderly Sudanese patient diagnosed with dengue fever. He was admitted, then 2 days after admission, the condition was complicated by atrial fibrillation, sagittal sinus thrombosis complicated by massive left temporal lobe infarction with haemorrhagic transformation and recurrent episodes of status epilepticus. After receiving the necessary care, his condition remained the same and no progress or deterioration was seen. Clinical discussion: Sagittal sinus thrombosis can happen due to several underlying causes. DENV can very rarely lead to such condition. The authors' patient developed this condition, which was later complicated by ischaemic stroke with haemorrhagic transformation and status epilepticus. In addition to a familial history of DVT and a history of myocardial infarction, our patient also acquired cardiac mural thrombus and DVT throughout his illness, which increased the suspicion of a protein C, protein S, or antithrombin 3 deficiency. Conclusion: Sagittal sinus thrombosis with haemorrhagic infarction associated with thrombocytopenia is a very rare kind of stroke that occurs in dengue. Dengue as a pathogenic mechanism of ischaemic stroke requires validation with further data.

Biallelic TYR and TKFC variants in Egyptian patients with OCA1 and new expanded TKFC features.

BACKGROUND: Oculocutaneous albinism type1 (OCA1) is caused by the TYR gene's homozygous and compound heterozygous variants. TKFC gene variants cause triokinase & FMN cyclase deficiency syndrome with variable multisystemic disorders. OBJECTIVES: To determine the potential disease-causing variants in two deceased patients presenting atypical OCA1 features by demonstrating three generations for a single family. The two deceased neonates had severe skeletal abnormalities and fatal hypertrophic cardiomyopathy. We also explored the potential mechanisms for the causative relationship between TKFC and multisystem disorders. PATIENTS AND METHODS: Due to the new emerging symptoms that weren't reported before with the TYR gene, the following methods were performed: Sanger sequencing for the TYR gene, followed by whole exome sequencing, co-segregation, and computational analyses. RESULTS: Extensive parental consanguinity was found, and consequently an autosomal recessive mode of inheritance was prioritized. Upon performing sequencing and segregation data, the following has been confirmed: positive co-segregation of nonsense homozygous NM_000372.5:c.346C > T p.(Arg116*) variant in TYR gene and multisystem disease-missense homozygous NM_015533.4:c.598G > A p.(Val200Ile) variant in TKFC gene in the two affected index patients who deceased due to hypertrophic cardiomyopathy. Using computational analysis, we found that c.598G > A p.(Val200Ile) pathogenicity has led to the failure of L2-K1 active site closure due to the potential differential fluctuation between valine and isoleucine residues. Subsequently, disruption of endogenous DHA phosphorylation was found. Two potential mechanisms exploring the causative relationship between TKFC gene and multisystem disorders have been suggested. CONCLUSIONS: This study presented a first family with the co-existence of biallelic variants in TYR and TKFC genes associating severe skeletal abnormalities and lethal hypertrophic cardiomyopathy. Neither of these genes would have been pursued in the standard genetic counseling. Such discovery is paving the way for more efficient genetic counseling. Comparing TKFC results with literature data showed that our relevant expanded TKFC variant is the 3rd worldwide.

Cost-effectiveness of ace inhibitors versus ARBs in heart failure management.

BACKGROUND: Heart failure is a chronic condition that imposes a significant burden on healthcare systems worldwide. Effective management is crucial for improving patient outcomes and reducing costs. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are widely used to manage heart failure by reducing cardiac strain and preventing disease progression. Despite their common use, ACE inhibitors and ARBs differ in mechanisms, cost, and potential side effects. ACE inhibitors have long been the standard treatment, while ARBs are often prescribed to patients intolerant to ACE inhibitors, particularly due to side effects like cough. Given these differences, evaluating the cost-effectiveness of these treatments is essential. This study compares the cost-effectiveness of ACE inhibitors and ARBs from a healthcare system perspective, considering both direct medical costs and health outcomes. METHODS: A cost-effectiveness analysis was conducted using a decision-analytic Markov model to simulate heart failure progression in a hypothetical cohort. Data inputs included clinical trial outcomes, real-world effectiveness data, direct medical costs (medications, hospitalizations, monitoring), and utility values for quality of life. The primary outcome measures were the cost per quality-adjusted life year gained and the incremental cost-effectiveness ratio. Sensitivity analyses tested the robustness of results, and subgroup analyses were conducted based on age and disease severity. RESULTS: The base-case analysis showed that ACE inhibitors were associated with lower overall costs and slightly higher quality-adjusted life years than ARBs. Sensitivity analyses revealed that variations in key parameters, such as transition probabilities, mortality rates, and healthcare expenses, had limited impact on the overall cost-effectiveness conclusions. Subgroup analyses indicated that ACE inhibitors and ARBs exhibited similar cost-effectiveness profiles for patients aged <65 and ≥65 years. However, among patients with severe heart failure, ARBs demonstrated a higher incremental cost-effectiveness ratio compared with ACE inhibitors, suggesting reduced cost-effectiveness in this subgroup. CONCLUSION: ACE inhibitors are likely a more cost-effective option for managing heart failure than ARBs, particularly from a healthcare system perspective. The findings underscore the importance of tailoring treatment decisions to individual patient factors, preferences, and clinical conditions, providing valuable insights for healthcare policy and practice, particularly regarding cost-effectiveness across patient subgroups.

A Study in Wad Madani, Sudan: Are We Documenting Operation Notes Effectively?

BACKGROUND: Operative notes represent the critical record of a surgical procedure, encompassing comprehensive details encountered throughout the operation. Recognizing the importance of comprehensive documentation, the Royal College of Surgeons (RCS) developed the Good Surgical Practice guidelines, which emphasize accurately recording every procedure and specifying the necessary parameters for each operative note. These guidelines help maintain high standards of surgical care and patient safety. METHODS: A retrospective review of 88 orthopaedic surgery operative notes for fracture neck of femurs was conducted at Gezira Centre for Orthopedic Surgery and Traumatology (GCOST) from March 12 to May 28, 2022. The review assessed 18 parameters against RCS guidelines. Statistical analysis was performed using Statistical Product and Service Solutions (SPSS, version 25.0; IBM SPSS Statistics for Windows, Armonk, NY), which facilitated comprehensive data examination. RESULTS: In 37 cases (42.05%), the operation notes were written by a medical officer. In 29 cases (32.95%), an orthopaedic resident authored the notes. A specialist documented the notes in 21 cases (23.86%), and a consultant wrote the notes in one case (1.14%). Over 90% of the notes included surgeon and assistant names, procedure names, operative diagnoses, operative procedures, prosthesis details, deep vein thrombosis (DVT) and antibiotic prophylaxis, and signatures. The name of the theatre anaesthetist, elective/emergency details, and additional procedures with reasons were absent in all notes. Less than 50% of the notes documented the time of the procedure, type of incision, operative findings, anticipated blood loss, closure technique specifics, and complications. CONCLUSION: The study emphasizes the shortcomings in the operating notes, underscoring the necessity for training initiatives to enhance the recording by medical officers and orthopaedic trainees. Implementing structured templates that adhere to RCS standards can improve the comprehensiveness and consistency of operating notes, effectively resolving existing discrepancies. Regular audits and feedback sessions are essential for identifying and rectifying persistent issues. It is recommended to arrange workshops and seminars to educate medical officials and trainees on the skills of efficient note-taking and thorough documentation procedures.

Effect of the "aSSKINg" Model in Reducing Pressure Ulcer Risk: A Comparative Study Using the Braden Risk Assessment Score.

Pressure ulcer is considered a common and costly problem in the care of patients. Prevention and management of pressure ulcer are very important due to the high cost of treatment and the adverse consequences of pressure ulcer. This study aimed to evaluate the effect of implementing "aSSKINg" model in reducing pressure ulcer risk. This study used a before- and after-intervention quasi-experimental design. This study was performed on 60 patients who were not randomly selected and assigned in to control and study group. The data collection tool was a 3-part sheet (Braden scale, skin health assessment, and Pressure ulcer assessment). The incidence of pressure ulcer was 19 (60.0%) in the control group versus 9 (30.0%) in the study group with statistical significant differences. The most common site of pressure ulcer was coccyx (6 [31.6%]) in the control group and Heel (3 [33.3%]) in the study group. The application of "aSSKINg" model in the patients with pressure ulcers is effective in reducing the incidence and severity of pressure ulcers.

Incidence and prevalence of autoimmune diseases in China: A systematic review and meta-analysis of epidemiological studies.

Background: Autoimmune diseases account for a substantial burden of disease in high-income countries, including Europe and North America. However, their epidemiology remains under-researched in other regions. We examined the incidence and prevalence of eight autoimmune diseases in the adult Chinese population through a systematic review of epidemiological studies. Methods: We searched OvidSP MEDLINE and Google Scholar from 1995 to 2023 (inclusive) for articles on the incidence or prevalence of autoimmune thyroiditis (AT), Graves' disease (GD), type 1 diabetes mellitus (T1D), multiple sclerosis (MS), Crohn's disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We included studies from mainland China, Taiwan, Hong Kong or Macau. The study is registered with PROSPERO (CRD42021225842). Findings: We retrieved 2278 records, of which 62 studies (161 estimates) were included in the systematic review, and 42 studies (101 estimates) were included in the meta-analysis. Pooled fixed-effects estimates for incidence of CD, UC, MS, T1D and SLE were 0.22 (95% CI 0.21-0.23), 1.13 (1.10-1.17), 0.28 (0.26-0.30), 2.20 (1.70-2.84) and 4.87 (4.21-5.64) per 100,000 persons, respectively. For RA, one study estimate was included, with an incidence of 15.8 per 100,000 persons. Fixed-effects estimates for the prevalence of CD, UC, MS, SLE, RA, GD and AT were 3.73 (95% CI 3.68-3.78), 16.11 (15.93-16.29), 4.08 (3.95-4.21), 93.44 (92.27-94.63), 104 (103-106), 450 (422-481) and 2322 (2057-2620), respectively, per 100,000 persons. Across all conditions, women were almost twice as likely as men to be diagnosed with an autoimmune disease. Interpretation: There is marked variation in the frequency of autoimmune diseases among Chinese adults. We estimate that 2.7-3.0% (>31 million people) of the adult Chinese population have one or more autoimmune diseases, comparable to Western populations, with the majority of the burden from autoimmune thyroid diseases and rheumatoid arthritis.

Acyl Hydrazides as Insecticides: Synthesis, Biochemical, Structure-Activity Relationship Studies and Insecticidal Activity of some IGRs Analogues Against Spodoptera littorallis (Boisd.).

The exponential rise in pesticide resistance to conventional chemical pesticides is another major factor driving the development of novel insecticidal active agents. One approach to solving this problem is to investigate novel classes and environmentally safe insecticidal chemicals with a variety of modes of action. Among these techniques is the creation of novel tebufenozide derivatives. Tebufenozide belongs to the insect growth regulator class of insecticides and is regarded as one of the safest chemical insecticides ever. The toxicological and biochemical efficiency of each analog was assessed against the Spodoptera littoralis pest in both its second and fourth instar larvae. The bioassay results show that compound 7 was the most effective insecticidal agent, with LC50 values of 10.6.5 and 18.7 mg/L against S. littoralis larvae in their second and fourth instar larvae, respectively. Finally, it was shown how treatment with the LC50 of the examined substances affected the activity of many enzymes involved in the cuticle production of S. littoralis larvae in their fourth instar. From this study, it was concluded that Acyl hydrazide are helpful for the management of S. littoralis and will be an effective replacement for other synthetic insecticides.