We appreciated to read the article by Cohen et al. about a 45yo male suspected of having developed Parkinson’s disease (PD) due to infection with SARS-CoV-2 [1]. It was concluded that SARS-CoV-2 may trigger the development of PD [1]. We have the following comments and concerns.

Strong arguments against a causal relation between SARS-CoV-2 and PD in the index patient are that the cerebro-spinal fluid (CSF) was negative for virus-RNA and that no antibodies against the virus were detected in the CSF, Thus, it is unlikely that SARS-CoV-2 ever had entered the CSF space. The main pathways considered via which the virus enters the brain include retrograde axonal migration after invagination of SARS-CoV-2 at taste buds or olfactory epithelial cell membranes, hematogenic spread of the virus to the brain, or transmigration via the blood brain barrier (BBB) by using immune cells as transport vehicles [2]. Furthermore, there is little evidence for SARS-CoV-2 in dopaminergic neurons of the substantia nigra. Only in a single study it is mentioned that SARS-CoV-2 may enter dopaminergic neurons [3] and only a single additional case of PD due to SARS-CoV-2 has been reported [4]. Whether PD was triggered by antibodies against virus antigens which cross-reacted with cell membrane components of dopaminergic neurons, remains speculative.

More likely than the infection with SARS-CoV-2 is labetalol having triggered the development of PD. Labetalol is a combined alpha- and beta-blocker and from beta-blockers, particularly propranolol, it is well-known that they increase the risk of developing PD [5]. Also amlodipine has been reported to cause PD [6]. Since various other drugs may trigger the development of PD as well, we should know the entire medication the patient received during hospitalisation. Patients with Sjögren syndrome have an increased risk of developing PD, particularly when treated with chloroquine, a drug frequently given to COVID-19 patients. Thus, we should know if the patient received chloroquine.

Overall, the report by Cohen et al. has some shortcomings and raises doubts about the alleged causal relation between SARS-CoV-2 and PD. As long as there are not more reports suggesting that SARS-CoV-2 triggers the development of PD, as long as there are no indications from prospective studies for a causal relation between SARS-CoV-2 and PD, and as long as there is no increase in the prevalence/incidence of PD since the outbreak of the pandemic despite >30 Mill infected subjects worldwide, a causal relation between SARS-CoV-2 remains speculative.

With interest we read the review article by Margolin et al. about the causes, work-up, and treatment options of diplopia (double vision) [1]. Diplopia may be due to affection of one or both eyes. Diplopia may be permanent or transient. The author concluded that “careful history taking and basic examination skills described in the article should allow a neurologist to make an accurate diagnosis in most cases” [1]. We have the following comments and concerns.

The main shortcoming of the study is that a number of disorders manifesting with diplopia were not included in this review. The most prevalent among these disorders is myopathy of extra-ocular muscle. Myopathy is a major differential diagnosis of diplopia, which may or may not be associated with concomitant ptosis. Diplopia may occur in primary (genetic) and secondary (acquired) myopathies. 

Among the muscular dystrophies, diplopia has been particularly reported in myotonic dystrophy [2] and oculo-pharyngeal muscular dystrophy [3]. Among the congenital myopathies diplopia has been most frequently described in nemaline myopathy [4]. The most prevalent myopathic cause of diplopia is metabolic myopathy. Among the metabolic myopathies, double vision is a hallmark of mitochondrial disorders (MIDs). Diplopia occurs in syndromic and non-syndromic MIDs. Among the syndromic MIDs, diplopia occurs most frequently in patients with progressive external ophthalmoplegia (PEO), which may be due to single or multiple mtDNA deletions, mtDNA depletion, or due to point mutations in nDNA or mtDNA located genes encoding for mitochondrial proteins. Diplopia is also a frequent feature of Kearns-Sayre syndrome or Leigh syndrome. Among the hereditary transmission disorders (congenital myasthenic syndromes) diplopia has been reported in patients carrying rapsyn mutations [5]. Among the channelopathies. paramyotonia congenita may manifest with double vision.

Among the secondary myopathies diplopia may occur in sarcoid orbital myopathy [6]. Double vision may be a dominant manifestation of oculomotor, ocular neuromyotonia [7]. Double vision can be a manifestation of drug-induced myopathy, such as PD-1 myopathy which is due to programmed death inhibitors [8]. Other drugs causing diplopia include tremelimumab, durvalumab [9], or isotrenoin. 

Various subtypes of Guillain-Barre syndrome (GBS), particularly Miller- Fisher syndrome (MFS) may manifest with double vision. More rarely, acute, inflammatory, demyelinating polyneuropathy (AIDP), acute, motor, axonal neuropathy (AMAN), or Bickerstaff encephalitis may manifest   with   double   vision.   Diplopia   may   be   a   manifestation   of neuroborreliosis. Not to forget, thiamine deficiency, manifesting as Wernicke encephalopathy or beri beri, may present with double vision among other typical manifestations [10].

The author also did not consider double vision due to orbital compartment syndrome due to carotid cavernous fistula. Primary or secondary orbital tumours should be also considered as rare causes of diplopia. Neurologist and ophthalmologist should also consider benign or malign neoplasms of the cerebrum as causes of diplopia. Diplopia has been particularly reported in association with pituitary adenoma, but also in association with lipoma or lymphoma. 

Overall, work-up for diplopia should include search for primary and secondary myopathy, for immune-mediated neuropathies, for  thiamine   deficiency,  benig and malign neoplasms, traumatic brain injury, and for orbital tumours. Work-up for these neglected causes of diplopia is crucial as some of them respond favourable to treatment. Early treatment may result in a better outcome than delayed application of treatment.

With interest we read the article by Norose et al. about the histological and immune-histological findings of islet cells in two patients with mitochondrial diabetes [1]. One patient was diagnosed with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome due to the variant m.3243A>G (patient-1) and the second patient was diagnosed with myoclonic epilepsy with ragged-red fibers (MERRF) syndrome due to the variant m.8344A>G [1]. Patient-1 required insulin, whereas patient-2 did not require any anti-diabetic treatment [1]. It was concluded that the severity of diabetes correlates with the severity of the histological and immune-histological findings on autopsy [1]. We have the following comments and concerns.

We do not agree with the conclusions that the different histological findings in the two patients correlate with the severity of diabetes. First, MELAS and MERRF are completely different disorders, why simply the genotype can explain the difference between the two patients. Second, phenotypic expression of mtDNA variants strongly depends on heteroplasmy rates, mtDNA copy number, and the haplotype [2]. Thus, it would be interesting to know if heteroplasmy rates and mtDNA copy numbers were different in islet cells or other clinically affected tissues between the two patients. We should also know if the two patients carried the same haplotype or not. Furthermore, we should know if there were alterations in the nuclear background and if the two patients had variable co-morbidities. Third, differences in histology and immune-histology could be also due to previous pancreatitis in either patient. Pancreatitis has been repeatedly reported as a clinical manifestation of mitochondrial disorder (MIDs) [3], why we should know if the previous history was positive for acute or chronic pancreatitis in either patient or if post-mortem histological findings on autopsy were indicative of previous pancreatitis. Fourth, we should know if there were any indications for affection of the cellular immune system in either patient, which has been previously reported [4], and if titers of antibodies against islet cells or mitochondria were different between the two patients.   

Furthermore, we do not agree that atrophy of islet cells necessarily means reduced production of insulin. Morphology not necessarily correlates with function. Thus, we should be informed about serum insulin levels and serum levels of the C-peptide to assess if islet cell function was truly reduced or not.

Since both MELAS and MERRF syndrome are multisystem diseases, potentially affecting liver and frequently the muscle [5], we should know if elevated blood glucose was due at least partially due to increased solution of liver or muscle glycogen or if gluconeogenesis was increased.

Since patient-2 had a HbA1c value of 6.9% (n, 4.6-6.2%) and diabetes was diagnosed, we should know why no anti- diabetic drugs or insulin were given. Was blood glucose well-controlled simply by diet?

Missing are the current blood chemical findings and the medication the two patients were taking at the time of decease. From various drugs it is known that they are potentially pancreato-toxic (e.g. valproic acid). Serum lactate may influence blood glucose levels as well and may   have    been different between the two patients.

Overall, the interesting, valuable study has some shortcomings which should be addressed before drawing final conclusions. Particularly, we need to know more about the genetic background, the current medication, and about the comorbidities of both patients before attributing different severity of diabetes only to different morphology of islet cells.

With interest we read the article by Piotrowska-Nowak et al. [1] about the influence of haplotypes and single nucleotide polymorphisms (SNPs) of the mitochondrial DNA (mtDNA) on the penetrance of the primary Leber’s hereditary optic neuropathy (LHON) mutation m.11778G>A in MT-ND4 in 47 unrelated Polish male patients. The authors concluded that haplogroup K and several mtDNA SNPs could determine the penetrance of this variant in the investigated cohort [1]. We have the following comments and concerns.

The authors are obviously not convinced about the significance of their results since the conclusions are speculative. The sample size is definitively too small to draw conclusions about the influence of the haplotype or SNPs on the penetrance of the primary LHON mutation m.11778G>A. From 5 patients carrying the haplotype K (11%) it cannot be calculated that haplotype K is responsible for the penetrance of the primary LHON mutation m.11778G>A. Furthermore, the distribution of SNPs in LHON patients and controls is not convincing as a factor determining the m.11778G> penetrance. There was no difference in the number of transitions and transversions between the two groups. The increased number of SNPs in the complex-IV regions in controls argues against causality. One would expect and increased number of SNPs in the patient group. Additionally, one would rather expect and increased number of SNPs in complex-1 regions but not complex-IV regions. 

We do not agree with the statement that “symptoms in LHON are limited to a single organ” [1]. LHON, like all other mitochondrial disorders (MIDs), is a multisystem disease, either already at onset of the disease or becomes a multisystem condition during the disease course. Though being a mono-organ condition in the vast majority of the cases at onset, several other organs or tissues become affected in LHON with progression of the disease (LHON plus) [2,3]. Only rarely, is spontaneous recovery of the abnormalities observed [4].

We do not agree with the notion that LHON is the most common MID [1]. The most common of the MIDs are the non-syndromic MIDs. Among the syndromic MIDs the most common is mitochondrial encephalopathy, lactic acidosis and stroke-like episode (MELAS) syndrome. Prevalence figures of syndromic MIDs vary largely between countries and regions.

We also do not agree with the statement that “the optic nerve is the tissue affected in LHON” [1]. The primary site of affection is the retina [5] where the primary pathophysiologic processes occur in the retinal ganglion cells (RGCs). Their neurites are secondarily affected leading degeneration and thus   secondary optic atrophy [5].

Unclear remains if all 47 included patients also manifested clinically or were asymptomatic carriers of the m.11778G>A variant. It is also unclear how many of the included patients received idebenone or not.            

Overall, the study has a number of shortcomings which need to be addressed before drawing final conclusions. The authors could not unequivocally demonstrate that haplotypes or mtDNA SNPs significantly influence the penetrance of the m.11778G>A variant. Since the vast majority of the respiratory chain complex-1 (RCC-1) subunits are nuclearly encoded, it is more likely that SNPs in nDNA genes encoding RCC-1 subunits than mtDNA SNPs influence the penetrance of the m.11778G>A variant. Warranted are more in-depth studies on the function of RCC-1 subunits and how the nuclear background influences the penetrance of mtDNA variants.

With interest we read the article by Heskamp et al. [1] about a prospective muscle MRI-study of 27 patients with myotonic dystrophy type-1 (MD1) who underwent either cognitive behavioural therapy (n = 18) or graded exercise plus behavioural therapy (n = 9). It was concluded that behavioural intervention targeting physical activity increases lower extremity muscle cross-sectional area [1]. We have the following comments and concerns.

A shortcoming of the study is that it is unclear which patients described previously [2,3] were included in the present study. In the article to which the authors refer, 33 MD1 patients were investigated [2] but the present study included only 27 patients since only these 27 underwent follow-up MRIs. Which were the 6 patients that were excluded and why? 

A further shortcoming is the application of the DM1-Activ scale to document graded exercise. Since the scale consists of 25 items describing activities of daily living, which can be assessed at three grades by the patient, the total “exercise” carried out was different in each patient, thus not standardised. We should know if a “graded exercise module” means that the patient filled in the DM1-Activ scale repeatedly. Ii is unclear which cut-offs were applied to define “exercise”. Furthermore, we should know how often during the 10 months observational period the form was filled out and how it was controlled that patients filled out the form honestly. 

Another shortcoming is that comparisons were carried out only between the standard care and the intervention group but not between the graded exercise and behavioural therapy group. This comparison is crucial to see if exercise truly had a better effect than behavioural therapy alone. 

Lastly, MD1 is a multisystem disease, affecting additionally the endocrine organs. Since muscle performance, composition, and morphology may strongly depend on endocrinologic parameters, [4] we should know if hormone levels differed between patients or groups and between inclusion and follow-up. Of particular interest are FGF-21 levels, which are increased in MD1 [5]. 

Overall, it cannot be excluded that the MRI changes reported reflect the effect of behavioural therapy alone or variable affection of endocrine organs but do not reflect graded exercise at all.

With interest we read the article by Kerr et al. about the diagnostic work-up of 36 patients with confirmed mitochondrial disorder(MID) (MID-group) and 80 patients with suspected MID but yet unconfirmed diagnosis (NO-group) by means of next generation sequencing(NGS).[1] In the MID-group MID was diagnosed upon a traditional approach.[1] The authors found that bigenomic sequencing(BGS) confirmed the diagnosis in 13/36 MID-patients and detected new pathogenic variants in 3 other MID-patients. In the NO-group one new MID-patient was identified by NGS.[1] We have the following concerns.

We do not agree with the conclusions that bigenomic sequencing(BGS), consisting of nWES and optimised mtDNA analysis, should be the first step in investigating suspected MIDs.[1] BGS confirmed an already known diagnosis in only 13/36 patients, and provided a new diagnosis in only 1/80 patients with suspected MID. How do the authors explain that 20 patients with a definite MID had a negative genetic test. This is unusual particularly as the diagnosis MID was supported by different methods. 

Furthermore, we should know why only 36 of the 115 patients with confirmed MID underwent NGS. Was this due to pecuniary reasons, due to absent consent, or unavailability of invited patients? 

Of the 390 patients referred for suspected MID according to figure 1, 69 had another diagnosis according to table 1. However, “unclassified neurodegenerative disease” is no “other” diagnosis. Furthermore, it is surprising that sepsis, juvenile osteoporosis, and bronchogenic lung carcinoma, as listed in table 2, initially suggested MID. 

In table 2 the authors use the term “bilateral bulbar neurosis” [1]. We assume that this in an error and actually should be “bilateral retrobulbar optic neuritis”.

Overall, diagnosing MIDs should be based not only on NGS but also on traditional procedures. NGS not only provides false positive and false negative results but still has a low sensitivity.

With interest we read the article by Forcelledo et al. about a 50 years-old female with MELAS due to the variant m.3243A>G who predominantly manifested with intestinal pseudo-obstruction (IPO), requiring cecostomy, and lastly colectomy [1]. The further course was rapidly progressive and the patient deceased from multiorgan failure [1]. We have the following comments and concerns.

MELAS is usually a multisystem disorder affecting not only the brain, nerves, and muscles but also the ears, eyes, endocrine organs, heart, gastro-intestinal tract, kidneys, bone marrow, and the skin [2]. We should be told in which organs the reported patient manifested clinically in addition to the gastro-intestinal tract, the brain and the kidneys. Knowing the number of organs/tissues affected at onset or becoming affected during the progression is crucial for assessing the speed of progression and the outcome.

Gastro-intestinal manifestations of MELAS are well appreciated [3] and may not only include IPO, bloating, vomiting, diarrhoea, constipation, gastro-intestinal reflux, distension, but also poor appetite, sicca syndrome, gastro-intestinal sphincter dysfunction, postprandial abdominal pain, pancreatitis, hepatopathy, pancreatic cysts, diverticulosis, recurrent bowel perforations with intra-abdominal abscesses, and pneumatosis coli [3].

Interestingly, the second episode of IPO was associated with a stroke-like episode (SLE) [4]. We should be told about the clinical manifestations of this SLE and if also other episodes of IPO were associated with SLEs. Recently, it has been suspected that episodes of IPO may trigger the occurrence of SLEs [5]. Thus, we should know if other IPO episodes were also associated with SLE and if cerebral MRI showed the typical features of a stroke-like lesion (SLL) [6]. Given the fact that IPO is associated with massive stress, it is conceivable that IPO indeed triggers a SLE. 

A shortcoming of the study is that the heteroplasmy rate of the m.3243A>G variant has not been provided. Knowing heteroplasmy rates in various tissues is crucial to assess the clinical course and outcome of a patient. We should also be informed if the mtDNA copy number was reduced or normal.

Since the m.3243A>G variant is transmitted via the maternal line in 75% of the patients, we should know if the family history was positive for mitochondrial disorder (MID), in particular MELAS. Of particular interest is the mother and other first-degree relatives. We should be told if any of the first-degree relatives carried the m.3243A>G variant or manifested with a similar or variant phenotype or if the variant had occurred spontaneously in the index patient.

Overall, this interesting case has a number of shortcomings, which should be met before drawing conclusions as those provided. There is a need to report heteroplasmy rates, degree of multiorgan involvement, clinical and genetic status of first-degree relatives, and clinical manifestations of the SLE. MELAS with rare phenotypes should be thoroughly investigated and extensively described to capture the entire phenotypic spectrum of this fascinating disease. It is conceivable that IPO triggers SLEs.

The main limitation of the study by Kanberg et al. [1] is that neurological symptoms were assessed without confirmation that neurons/glial cells were affected. No cerebral imaging studies, CSF studies, nerve conduction studies, cerebral angiographies, EEGs, or electro-myographies were provided. Missing is also a clinical neurological investigations to objectify the reported symptoms.

Fatigue may not only be a neurological symptom but may also originate from pulmonary, cardiac, psychiatric, endocrine, or renal involvement in COVID-19.[2] Thus, it is crucial to assess in how many of the included patients fatigue was non-neurological. “Changes in cognition” may not only be neurological but may occur together with fever, 

A further limitation is that the current medication and the anti-COVID-19 treatment were not included in the evaluation. From a number of drugs given for COVID-19 it is known that they can be neurotoxic or glial-toxic [3,4] why it is essential to know the treatment for COVID-19. In this respect we also need to know how many of the 100 patients required mechanical ventilation as it is usually associated with the requirement for sedation, muscle relaxation, analgesia, or anaesthesia. 

Missing is the differentiation between primary and secondary neurological impairment in COVID-19. Not only the virus and the immunological reaction against it may lead to CNS/PNS damage but also involvement of organs other than the CNS/PNS in COVID-19. Cardiac involvement may lead to cardio-embolism or arterial hypertension, which may cause PRES, vasoconstriction syndrome, or ICB. 

Overall, the interesting study has several limitations which challenge the results and their interpretation.

With interest we read the article by Baskaran et al. about a 22 months-old female with Leigh-syndrome (LS) due to a variant in SURF1, phenotypically manifesting with classical features of the syndrome [1]. We have the following comments and concerns.

A shortcoming of the study is that the causative SURF1 variant was not specified. Additionally, information if the variant occurred in the homo- or heterozygous form is missing.

Furthermore, we do not agree that LS is only caused by variants in genes encoding proteins responsible for the pyruvate-dehydrogenase complex, cytochrome-c oxidase, adenosine-triphosphate synthase subunit-6, or subunits of mitochondrial comples [1]. The spectrum of mutated genes causing LS is broader than mentioned in the introduction. Currently, mutations in about 75 different genes have been linked to LS [2]. 

Missing in the report is the family history. Since LS due to SURF1 mutations is usually transmitted via an autosomal recessive or dominant trait [3], we should know if other first-degree relatives were clinically affected or carried the variant. Of particular interest is the clinical presentation and genetic status of the mother and father of the index patient. 

Unfortunately, no details about seizure type, seizure frequency, type of anti-seizure drug (ASD) treatment, compliance, and effect or side effects of the AED treatment have been provided. Knowing the exact AED treatment is crucial as it may determine the outcome of these patients.

LS is usually a multisystem disease, in which not only the brain but also the eyes, ears, endocrine organs, heart, the gastro-intestinal tract, the kidney, the bones, or the skin can be affected. The index patient obviously manifested in the brain (epilepsy, hypotonia, ataxia, failure-to-thrive), the endocrine system (hirsutismus), gastro-intestinal tract (vomiting, diarrhoea, poor weight gain), the muscle (myopathy of limb and extra-ocular muscles), and other systems (dysmorphism, developmental delay). We should know if the patient was prospectively investigated for subclinical or mild involvement of other organs, such as the heart or the kidneys. Of particular interest is cardiac involvement since it may strongly co-determine the outcome of these patients [4].

Overall, the case report presented by Baskaran et al. has a number of shortcomings, which should be met before drawing final conclusions. We should know the mutation load in the index patient, the genetic status of the parents or other first-degree relatives, and the results of prospective investigations of the heart. More information about epilepsy in the index patient is warranted.

With interest we read the article by Aksoy et al. about a 46 years old female with myasthenia gravis (MG) due to antibodies against the acetyl-choline receptor (AchR) being treated with 120mg pyridostigmine per day in whom MG exacerbated in the course of an infection with SARS-CoV-2 (COVID-19) [1]. It was concluded that early immune-modulatory therapy may be more effective in terms of preventing permanent lung damage than standard first-line treatments in patients with MG [1]. We have the following comments and concerns.

A shortcoming of the study is that AchR antibody titers were not determined during hospitalisation and were not compared with pre-hospitalisation titers. Knowing AchR antibody titers during hospitalisation would allow assessing if MG truly exacerbated. Missing in this respect are results of nerve conduction studies (NCSs), such as repetitive nerve stimulation or single-fiber EMG to document exacerbation of MG during the viral infection. Since clinical manifestations of COVID-19 may mimic clinical manifestations of MG, differentiation between deterioration due to the viral infection or due to MG is often not possible upon clinical investigations alone. The presented data are not convincing with regard to exacerbation of MG. Symptoms and signs could be simply explained by the severe SARS-CoV-2 infection. 

A dosage of 120mg/d pyridostigmine is very low according to the recommendations of international neurological societies for treating MG [2]. We should know the reason why the patient was treated with such a low dosage. Was this due to the low body weight of the patient or due to only mild symptoms during the last 4y since onset of MG?

Certain drugs may exacerbate MG, such as chloroquine [3] or azithromycin [4]. We should know why the patient nonetheless received these drugs on admission. Missing is the complete list of drugs the patient was regularly taking prior to admission.

We do not agree with the statement that corticosteroids should be used with caution in MG patients. Steroids are the mainstay of generalised MG treatment particularly before immune-suppressive treatment becomes effective or during exacerbations. Steroids may not only improve clinical manifestations of MG but may also lower AchR antibody titers [5]. 

According to a recent review of SARS-CoV-2 infected patients with MG [6], there is no increase in the prevalence of MG since the outbreak of the COVID-19 pandemic, MG not necessarily deteriorates in SARS-CoV-2-infected patients, there is no increase in the frequency of complications, and there is no general need to modify the anti-myasthenic treatment in asymptomatic SARS-CoV-2-positive MG patients [6]. In symptomatic SARS-CoV-2 infected MG patients, however, there may be a need to modify and adapt immune-modulating treatment depending on the clinical presentaiton and disease course.

Overall, this interesting study has a number of shortcomings which should be addressed before drawing final conclusions. There is a need for confirmation of MG exacerbation by non-clinical investigations, to differentiate between manifestations of MG and COVID-19. Immuno-suppression should be considered in all COVID-19 patients given the often severe immune-response with lymphocyte depletion and chemokine and cytokine elevation in these patients.

Though severe side effects were not found in Ali’s investigation [1] and were not reported previously in adolescents following vaccinations with the mRNA-1273 SARS-CoV-2 vaccine(Moderna), there are several reports of severe adverse reactions to this vaccine in adults. 

 In a 22yo male with a history of mild COVID-19 6m prior, peri-myocarditis developed 3d after the first dose of the Moderna vaccine [2]. The patient markedly benefited from aspirin and colchicine [2].

A 77yo male developed immune encephalitis, myoclonus, and Sweet-syndrome 1d after the first Moderna dose [3]. He profited significantly from methyl-prednisolone.[3]

A 60yo male with a history of hepatitis-C, renal insufficiency, hypertension, and heart failure, presented with purpuric rash and thrombocytopenia (84000/µL) without major bleeding 2d after the first Moderna dose [4]. 

A 66yo male developed a large-area, painful blistering rash 1d after the second Moderna dose [5]. He benefited from mupirocin and prednisone.

One day after the second Moderna dose, a 34yo male developed myocarditis. Aspirin, colchicine, bisoprolol and rampiril were beneficial.

Though severe adverse reactions to Moderna are rarely reported, they might be harmful to those experiencing them.