Review on dietary supplements as an effective improvement of Alzheimer's disease:focus on structures and mechanisms

Alzheimer’s disease(AD),the major form of neurodegenerative diseases that can severely impede normal cognitive function,makes it one of the most common fatal diseases.There are currently over 50 million AD patients worldwide.The neuropathology of AD is perplexing and there is a scarcity of disease-modifying treatments.Currently,early diagnosis of AD has been made possible with the discovery of biological markers associated with pathology,providing strong support for the improvement of the disease status.The search for inhibitors of AD markers from dietary supplements(DSs)has become a major hot topic.Especially with the widespread use of DSs,DSs containing polyphenols,alkaloids,terpenes,polysaccharides and other bioactive components can prevent AD by reducing Aβdeposition,inhibiting tau protein hyperphosphorylation,reconstructing synaptic dysfunction,weakening cholinesterase activity,regulating mitochondrial oxidative stress,neuronal inflammation and apoptosis.This review summarizes the anti-AD effects of the main DSs and their bioactive constituents,as well as the potential molecular mechanisms covers from 2017 to 2023.Additionally,we discussed the opportunities and challenges faced by DSs in the process of AD prevention and treatment,aiming to further provide new perspectives for functional food development.

Severe liver injury due to herbal and dietary supplements and the role of liver transplantation

Herbal and dietary supplements(HDS)are increasingly used worldwide for numerous,mainly unproven health benefits.The HDS industry is poorly regulated compared to prescription medicines and most products are easily obtainable.Drug induced liver injury(DILI)is a well-recognized entity associated with prescription and over the counter medications and many reports have emerged of potential HDS-related DILI.There is considerable geographic variability in the risk and severity of DILI associated with HDS but the presentation of severe liver injury is similar with a hepatocellular pattern accompanied by jaundice.This type of injury can lead to acute liver failure and the need for liver transplantation.Patients will often fail to mention their use of HDS,considering it natural and therefore harmless.Hence physicians should understand that these products can be associated with DILI and explicitly ask about HDS use in any patient with otherwise unexplained acute liver injury.

Detection of illegally added drugs in dietary supplements by near-infrared spectral imaging

The application to detect ilally added drugs in dietary supplerments by near-infrared spectral imaging was studied with the focus on nifedipine,diclofenac and metformin.The method is based on near-infrared spectral images correlation cofficient to detect ilally added drugs.The results comply 100%with HPLC methods test results with no false positive results.

Drug and herbal/dietary supplements-induced liver injury:A tertiary care center experience

BACKGROUND Drug-induced liver injury(DILI)and herbal/dietary supplements(HDS)related liver injury present unique diagnostic challenges.Collaboration between the clinician and the pathologist is required for an accurate diagnosis and management.AIM To report our experience on the clinical-pathological findings of hepatic injury caused by drugs/HDS.METHODS A retrospective review of clinically proven cases of DILI/HDS who presented to our institution from January 1,2013 to December 31,2017 was performed.Slides were reviewed for histopathological patterns of injury and correlated with the causative agent.Out of 600 patients presenting with unexplained rise in liver enzymes undergoing biopsy,107 were suspected to have DILI/HDS.Of these,53 had a directly linked exposure to drug/herbal supplements.Fifteen patients were excluded for concurrent known liver disease.Thirty-eight patients with clinically proven DILI/HDS were finally included.RESULTS Thirty-eight cases of DILI/HDS with a male:female of 1:1.5 and mean age of 51±3 years were identified.DILI was identified in 84.2%cases while HDS injury in 15.8%.Acute hepatitis(42.1%)was the most common pattern of injury while granulomatous hepatitis(2.6%)was the least common.We found one case of acute-cholestasis due to rivaroxaban and two cases of cholestatic-hepatitis due to rizatriptan and trimethobenzamide-hydrochloride that,to the best of our knowledge,have not been previously reported.One case of steatohepatitis due to trimethoprim-sulfamethoxazole and three unusual cases of cholestatic-hepatitis with bile duct injury and steatosis due to dronedarone,C4-Extreme and hydroxycut,were also seen.Of our cohort,81.6%of the patients fared well with discontinuation of drug and 18.4%underwent transplant;of which 42.9%were deceased.CONCLUSION We describe the clinical findings,histopathological patterns of injury and clinical outcomes caused by drugs.In particular,we report a few previously unreported/rarely observed clinical and histopathological patterns of hepatic injury.

Beyond Nutrition Recommendations: What Healthcare Professionals Should Know about Dietary Supplements to Best Serve Their Patients

Although whole food nutrition will likely influence physical health more than any other lifestyle component besides exercise, the use of dietary supplements among men and women continues to be high. Due to this fact, it is imperative that healthcare professionals understand how supplements may impact overall health and wellness of their patients. With the majority of adults taking some form of dietary supplements and many concomitantly taking prescription medications, healthcare providers should be conscientious of adverse effects and interactions that may occur between dietary supplements and prescription drugs. As many consumers are misled by false marketing, healthcare providers should encourage them to be wary of exaggerated claims and direct them to products that are scientifically supported and safe. Continuing education for healthcare providers on dietary supplements is crucial, with new dietary supplement products constantly reaching the markets, in addition to new findings being made through clinical research and case studies. While some dietary supplements provide no meaningful benefit, many dietary supplements have been identified that can be used to ameliorate nutritional deficiencies and reduce the risk of some common health conditions. Others can serve to improve mental and physical performance, while truly enhancing health. This article presents relevant information on dietary supplements that will be useful to the healthcare professional.

Navigating the Nomenclature of a Purported “Dietary Supplement”: A Cautionary Tale for Consumers and Practitioners Regarding Tianeptine or “Gas Station Heroin”

Dietary supplement sales have surpassed $30 billion per year with their use becoming and remaining extremely popular amongst the general public. There are numerous bioactive components, both nutritive and non-nutritive, in dietary supplements with considerable efficacy in promoting health. However, there are many ways disallowed ingredients may enter the supplement pipeline with potentially toxic effects. Dietary supplements can be regulated (either pre- or post-market) as a drug, dietary supplement, a nutraceutical, new dietary ingredient (NDI), generally recognized as safe (GRAS) food ingredient, a food additive, or a food. A pharmaceutical drug (medication) is used to treat, cure, prevent, or diagnose a disease and is regulated by the FDA pre-market only and allowed by medical prescription, whereas the other labeling designations are largely regulated post-market. One such molecule with a labeling problem is tianeptine, which has global use as an efficacious, prescribed drug, while at the same time being considered a non-drug and potentially dangerous adulterant often referred to as gas station heroin. In this paper, we critically evaluate the use and labeling of this compound and attempt to clarify the conundrum surrounding its legal or illegal use. Tianeptine is effective and efficacious as an antidepressant in those responding poorly to selective serotonin reuptake inhibitors (SSRIs) and exhibits many medicinal characteristics of tricyclic antidepressants with fewer opioid-like side effects. As a result, sixty-six countries permit use of tianeptine as a prescription drug. At higher doses, tianeptine has recently been shown to exhibit significant potential for abuse and dependency along with toxicity. As such, the US does not recognize tianeptine as an FDA-approved drug or as a dietary supplement, nutraceutical, new dietary ingredient (NDI), GRAS ingredient, or a food. Instead, tianeptine is a synthetic adulterant of a dietary supplement and considered technically an unapproved food additive. In conclusion, tianeptine, although viewed as a safe dietary supplement by many, is illegal in the US despite benefits to many but toxicity to others that make it vital that consumers and healthcare providers learn to critically evaluate and navigate the often confusing nomenclature of a purported dietary supplement to convey to the public whether it is efficacious, safe, and legal.

Retrospective Assessment of Changes in Perceived Health Status during Continuous Use of a Dietary Supplement

Dietary factors play an important role in human health. Specifically, nutritional interventions may have an impact on the hypothalamic-pituitary axis resulting in positive health outcomes. A retrospective health status survey of 386 respondents was conducted to investigate the potential of a dietary supplement, NutrifiiTM Renew, for improving various health outcomes in comparison to a multivitamin/mineral control group. Among those who ingested Renew, 95% reported experiencing at least some improvement in one or more health categories. Compared to the multivitamin/mineral group, the Renew group reported earlier and/or greater improvements in several health status categories including sleep, reproductive health, memory, energy/stamina, skin and hair quality, flexibility, exercise recovery and feeling rested in the morning. A clear majority (84.9%) of Renew consumers reported experiencing noticeable improvement in some aspect of their health within one month. Among those who felt an improvement in sleep, most reported experiencing a change within one week. These improvements were likely due to the synergistic effects of L-arginine, L-citrulline, L-lysine, and botanical extracts on nitric oxide production, growth hormone (GH) release, and sleep quality. The observed improvements in skin elasticity and hair growth may be related to increased GH levels and IGF-1 production. Overall, these findings suggest that Renew may have potential as a dietary intervention for improving various health outcomes beyond those provided by multivitamin/mineral supplementation alone. Further studies are needed to confirm these findings and elucidate the underlying mechanisms of action.

Insights into skullcap herb-induced liver injury

This editorial addresses the growing concern of herb-induced liver injury(HILI),focusing on a unique case of Skullcap-induced HILI report.This editorial underscore the significant mortality rate linked to Skullcap-induced HILI,emphasizing the importance of vigilant monitoring and intervention.As herbal supplement usage rises,collaboration among clinicians and researchers is crucial to comprehend and address the complexities of HILI,particularly those involving Skullcap.

Dietary supplementation in patients with alcoholic liver disease: a review on current evidence

BACKGROUND：Alcoholic liver disease（ALD）is one of the main causes of liver disease worldwide.Although the pathogenesis of ALD has not yet been well elucidated,the oxidative metabolites of ethanol such as acetaldehyde and reactive oxygen species play a pivotal role in the clinical and pathological spectrum of the disease.This review summarizes the existing evidences on dietary supplements considered to have antioxidant,and/or anti-inflammatory properties,and their role in the management of ALD and the proposed mechanisms.DATA SOURCES：The present study reviewed all studies published in Pub Med,Science Direct and Scopus,from 1959 to2015,indicating the role of different dietary supplementation in attenuation of many pathophysiological processes involved in development and progression of ALD.Full-texts of citations were used except for those that were published in languages other than English.RESULTS：Significant progress has been made to understand the key events and molecular players for the onset and progression of ALD from both experimental and clinical studies;however,there is no successful treatment currently available.The present review discussed the role of a variety of dietary supplements（e.g.vitamin A,carotenoids,vitamins B3,C and E,in addition to antioxidants and anti-inflammatory agents）in treating ALD.It has been shown that supplementation with some carotenoids,vitamin B3,vitamin C,silymarin,curcumin,probiotics,zinc,S-adenosylmethionine and garlic may havepotential beneficial effects in animal models of ALD;however,the number of clinical studies is very limited.In addition,supplementation should be accompanied with alcohol cessation.CONCLUSIONS：Since oxidative stress and inflammation are involved in the pathogenesis of ALD,dietary supplements that can modulate these pathologies could be useful in the treatment of ALD.In addition to alcohol cessation,these supplements have shown beneficial effects on animal models of ALD.Clinical trials are needed to validate the beneficiary role of these supplements in patients with ALD.

Integrative techniques using acupuncture,Chinese herbal medicine,diet,and supplements for polycystic ovary syndrome:a case report

Patients with a diagnosis of polycystic ovary syndrome （PCOS） are on the rise. About 4%-12% of women are currently estimated to have this condition. It is hypothesized that PCOS appears in women who have long-standing insulin resistance （1R）, which leads to high androgen and testosterone levels; this ultimately disrupts their menstrual cycles. Some researchers attribute IR to genetic factors, although there have been only minute changes in the human genome in the past 20 000 years. However, even with a stable gene pool, genes can be turned on and offby the environment, food and air quality and toxin exposure.

FDA Approves First Dietary Supplement under New Drug Application with the Indication of Serious or Life-Threatening Illnesses

Background: Research began on botanical/herbal organisms to study plant cells. The idea behind this was that plant cells have basic similar actions as do animal cells (i.e., both are Eukaryotic cells). These cells can show what activity is produced from the Technology/Innovation behind ImunStem, without risk to animals or humans, and still retrieve data to verify the theory. By using plants and studying plant cell activity, then later comparing plant cell, animal cells, and human cell responses, it thus shows activity for all cell structures. The activity was also studied from patients taking ImunStem for the indication of Serious or Life-threatening conditions or diseases. Patient medical report results showed an overall improvement in bodily function as blood report results were compared. Patients that were administered ImunStem showed improvement in their overall health and patients with chronic disease had reduced pain as ImunStem was administered over time. The pain was reduced because the body was in the healing process and a reduction in inflammation would occur during healing and the patient’s health would improve. ImunStem was produced based on the theory that the product could rejuvenate the cell and bring the cell back to a homeostasis balance. This balance to the cell (through nutrition) can give the surrounding cells a homeostasis balance that may heal cells and tissues in the body. It is believed that the function of a Quantum Wave effect is explained through the discipline of Quantum Mechanics. The Quantum Wave may disrupt the subatomic particles that provide adhesion to allow the product through the cell wall and move to its target location. In Quantum Mechanics, particles have wavelike properties. The Schrödinger equation, for example, governs how these waves behave. Methods: Administration of ImunStem was given to patients in a life-threatening situation where no standard acceptable treatment was available and in which there was not sufficient time to obtain approval from the Institutional Review Board. Results: ImunStem showed positive medical results for patients with Serious or Life-threatening conditions or diseases, which prompted the US Food and Drug Administration (FDA) to move forward so patients could be provided treatment that was not otherwise available to them from their physicians/doctors. ImunStem was applied for and received its New Drug Application (NDA) No.: 204701 with the indication of Serious or Life-threatening conditions or diseases and National Drug Code (NDC) No.: 70642-001-01 on July 02, 2018. Golden Sunrise submitted an NDA application on January 07, 2013, November 05, 2018, and April 03, 2020 with a request for FDA Fast Track designation, Breakthrough Therapy designation, Accelerated Approval designation, and Priority Review program process are the pathway allowing the ImunStem product to receive acceptance by the FDA.

Spermotrend Improves Semen Quality and Infertility in Men with Varicocele —Spermotrend and Male Infertility

Background: Infertility affects 8% - 12% of couples globally, with approximately half of the cases reported in males. Oxidative stress is a common factor increased in the varicocele condition and particularly affects spermatozoa, due to their sensitivity to oxidative signals and testicular hypotrophy. The objective of this clinical trial is to study the effectiveness of Spermotrend in the improvement of sperm parameters in male infertility. Methods: A total of 170 males aged > 18 years with a diagnosis of infertility and varicocele were consecutively enrolled in a Phase II, open-label clinical trial. Spermotrend was administered 1 capsule (450 mg) orally every 8 hours for 6 months and was evaluated through semen analysis at 4 and 6 months of follow-up. Results: The trial results show a significant improvement following the administration of Spermotrend over 6 months in sperm concentration (44.1% at baseline vs. 64.1% at 6 months), sperm survival (28.2% with sperm survival ≥ 2 hours vs.56.5%), normalization of sperm morphology (31.2% vs. 72.9%). Varicocele condition decreased in all patients and, by the end of the study, 55.3% of patients had normal venous flow and dilation. Only 5.9% of the patients showed grade 2 varicocele at the end of the study, while 38.8% showed grade 1 varicocele, with no patients showing grade 3 varicocele. Regarding testicular hypotrophy, 90.6% of the patients completed the study with normalized testicular volume by recovering normal venous flow. Conclusion: A short-term course of Spermotrend may significantly improve sperm parameters associated with male infertility. Clinical Trial Registration: The clinical trial protocol was registered in the international clinical trial registry, ClinicalTrials.gov, with the code: NCT05222841 on 15/06/2021.

Effect of a novel dietary supplement on pH levels of healthy volunteers:a pilot study

OBJECTIVE： To examine the effects of a greens alkalizing dietary supplement on urinary pH levels in individuals with lower-than-average pH levels. METHODS： The present study investigated the effects of an alkalizing formula （Reserveage Wholeganic GreensTM） on four individuals who had average urinary pH levels below 6.0 for three consecutive days. Following the three-day, baseline period, participants received Reserveage Wholeganic GreensTM for four consecutive days and were instructed to continue to measure their urine pH levels. Paired samples t-tests were used to examine pH levels before and after a four-day treatment period with Reserveage Wholeganic GreensTM. RESULTS： Compared to baseline, mean urine pH levels in all volunteers were significantly higher following the supplementation with Reserveage Wholeganic GreensTM （5.89 ±0.20 vs 5.56 ± 0.23; P〈0.01）. Participants＇ pH levels were also significantly higher than baseline on days 5, 6, and 7 of the treatment period （P 〈 0.05）. Noteworthy, on day 7, participants＇ mean pH levels were significantly higher than at the beginning of the treatment period （6.03 ± 0.15 at day 7 vs 5.65 ± 0.24 at day 4; P 〈 0.01）. CONCLUSION： The findings of this study suggest that supplementation with Reserveage Wholeganic GreensTM has an alkalizing effect on the body and can increase the urine pH levels in individuals with lower-than-average pH levels.

Is Titration as Accurate as HPLC for Determination of Vitamin C in Supplements? <br/>—Titration versus HPLC for Vitamin C Analysis

Herein, the iodometric titration and HPLC-RP methods were compared for the determination of vitamin C in vitamin and mineral supplements. The methods were validated in terms of linearity, limits of detection (LOD), limits of quantification (LOQ), precision, and recovery by using vitamin standards and a reference material SRM 3280 (multivitamin/multimineral tablets) obtained from the National Institute of Standards and Technology (NIST). A total of 22 samples of vitamin supplements, randomly acquired in local markets of Sao Paulo (Brazil) were evaluated for content of vitamin C by these two methodologies. The precision expressed as RSD was lower than 5% for both methods. LOD was 3.6 μg/mL for HPLC and 1.0 mg for titration, while LOQ were 12.0 μg/mL and 3.0 mg for HPLC and titration, respectively. Percent recoveries (%) of spiked samples ranged from 98.7 to 100.5 for HPLC and from 98 to 104 for titration. The contents of vitamin C in SRM 3280 (Certified value = 42.2 ± 3.7 mg/g) were 40.2 and 42.1 mg/g when determined by HPLC and titration respectively. Statistically, there was no difference in the analysed vitamin C content for half of the samples, irrespective of the method applied. HPLC was more sensitive, but the titrimetric method was faster and consumed less reagent. Although both methods were accurate in determining the vitamin C content in SRM 3280, the matrix constituents of some vitamin supplements may have interfered with the analysis.

Effects of dietary high dose DHA omega-3 supplement in dry eye with meibomian gland dysfunction

AIM:To evaluate the clinical efficacy of dietary supplement of high dose DHA omega-3 in dry eye with meibomian gland dysfunction(MGD).METHODS:Prospective randomized double-masked,placebo-controlled clinical trial was conducted in mild to moderate dry eye patients with MGD.Patients have no history of taking any dietary omega-3 supplements before 3 mo.Patients were divided into two groups:24 patients in the omega-3 group and 26 patients in the placebo group.The omega-3 group received two capsules of Easyeye Dry?,total containing 600 mg of EPA and 1640 mg of DHA,while the placebo group received two capsules containing 3000 mg of olive oil.All patients take two pills once a day.The examination of MGD scores,tear break-up time(TBUT),corneal staining test(NEI),strip meniscometry(SM tube),and ocular surface disease index(OSDI)scores were performed at baseline,after 4 and 8 wk.RESULTS:A total of 50 patients were included.There were no differences in baseline characteristics between the two groups,such as age,sex,and other ocular examination findings.The TBUT,NEI,and OSDI scores significantly improved after 4 and 8 wk in both groups.While after 8 wk TBUT(6.00±1.62 s vs 5.08±1.28 s,P=0.034)and MGD score(7.2±1.8 vs 8.1±2.6,P=0.033)in the omega-3 group was more significantly improved than that of the placebo group.CONCLUSION:Dry eye with the MGD patient,a high dose of DHA omega-3 dietary supplement can improve TBUT and MGD score after 8 wk,effective in stabilizing the tear film.

Antioxidant Property of a Dietary Supplement of Moringa oleifera Leaves and Pleurotus ostreatus in Wistar Rats Subjected to Forced Swimming Endurance Test

The antioxidant property of Moringa oleifera leaves and Pleurotus ostreatus on swimming performance and related biochemical parameters were investigated in thirty adult male and female wistar rats. Purpose: The aim of the present study was to evaluate the antioxidant property of M. oleifera and P. ostreatus mixture in specific proportions in wistar rats. Material and Methods: The mushroom species and M. oleifera leaves were cultivated at the biotechnology laboratory of the University Cheikh Anta Diop de Dakar, Senegal. Oxidative stress in rats was induced by swimming. The dietary supplement was composed of a mixture of powders of Moringa oleifera and Pleurotus ostreatus in 2:1 ratio. Three groups received different doses of dietary supplements 500 mg/kg, 1000 mg/kg, and 1500 mg/kg, with one group being the stressed and the other the control group. Parameters in serum such as serum glutamyl oxaloacetate transaminase, serum glutamyl pyruvate transaminase, albumin, Testosterone, creatinine, and, oxidative stress parameters (catalase, reduced glutathione, and malondialdehyde) were measured. Results: Results showed that the dietary supplement has an effect on oxidative stress because it increases the activity of catalase and the level of cellular glutathione in rats. The 500 mg/kg dose would be the most appropriate dose for stressful conditions. The 1000 mg/kg dose would be the most appropriate dose for liver damage. Conclusion: This study shows that the antioxidant properties of M. oleifera leaves and Pleurotus ostreatus are demonstrated by their ability to improve body energy stores and tissue antioxidant capacity. The dietary supplement of M. oleifera leaves and P. ostreatus powders mixture could be good in stressful conditions.

Pigmentation Restored in Mutant Laboratory Strain of the Lady Beetle Coleomegilla maculata through Dietary Supplementation

A laboratory colony of Coleomegilla maculata (DeGeer), ye, selected for a pigmentation deficiency, was restored to near wild type cuticle coloration by adding crushed heads and wings of the red colored parental strain to the diet. While the wings and other colored portions of the cuticle re-gained the red color, the eyes of the pigmentation deficient insects were not changed from the pale mutant form. Plant derived carotenes lycopene and beta-carotene did not restore the mutant beetles to a visibly distinguishable red color. An additional pigmentation deficient mutant strain, gold, partially recovered red cuticle color when provided with diet containing pigmented insect particles. This work represents the first rescue of a color phenotype in a lady beetle.

Impact of dietary supplementation of one-carbon metabolism on neural recovery

In the cell,one-carbon metabolism modulates nucleotide synthesis,DNA repair,as well as methylation through the reduction of homocysteine（Figure 1）.High levels of plasma homocysteine have been associated with negative health outcomes in humans（Murray et al.,2017）.Folates,B-vitamins,are a major component of one-carbon metabolism and play an important role in brain function.Specifically,they are involved in nucleotide synthesis,DNA repair,methylation,second messenger systems,ion channels,protein,

Mixed vitamin C and zinc diet supplements co-administered with artemether drug improved haematological profile and survival of mice infected with Plasmodium berghei

Iron and zinc deficiencies is common in malaria endemic areas and contributes to morbidity.Vitamin C and zinc combined supplements have been hypothesized as a remedy.This study evaluated the effect of different combinations of vitamin C and zinc on haematological parameters and mortality of Plasmodium berghei-infected mice(Mus musculus).A three-week trial was carried out to assess haematological changes and mortality of mice after 3-day artemether treatment co-administered with vitamin C-zinc supplements.Grouping was based on combinations of vitamin C and zinc.Weight,packed cell volume(PCV),white blood cell count(WBC),red blood cell count(RBC),haemoglobin concentration(HB),and mortality were assayed weekly.The supplement improved PCV,HB,mean cell volume(MCV)and mean cell haemoglobin(MCH).Mice mortality was higher in the absence of the supplement,though the difference was not significant(x^2=5.214,P=0.5167).Parasitaemia was not reduced by the supplement.A 30:70 vitamin C-zinc supplement performed better than other combinations used.Therefore,vitamin C-zinc supplement play roles in the management of malaria,since they improved PCV and HB,and lowered mortality rate,complementing the therapeutic effect of artemether.

Pigmentation Restored in Mutant Laboratory Strain of the Lady Beetle <i>Coleomegilla maculata</i>through Dietary Supplementation

A laboratory colony of Coleomegilla maculata (DeGeer), ye, selected for a pigmentation deficiency, was restored to near wild type cuticle coloration by adding crushed heads and wings of the red colored parental strain to the diet. While the wings and other colored portions of the cuticle re-gained the red color, the eyes of the pigmentation deficient insects were not changed from the pale mutant form. Plant derived carotenes lycopene and beta-carotene did not restore the mutant beetles to a visibly distinguishable red color. An additional pigmentation deficient mutant strain, gold, partially recovered red cuticle color when provided with diet containing pigmented insect particles. This work represents the first rescue of a color phenotype in a lady beetle.