[Two cases of anti-nuclear matrix protein 2 antibody-positive dermatomyositis sine dermatitis with severe diffuse subcutaneous edema and dysphagia].

Case 1 involved a 68-year-old woman who was admitted to our hospital because of muscle weakness, diffuse subcutaneous edema, dysphagia, and an elevated serum creatine kinase level that had worsened within the previous month. Case 2 involved a 78-year-old woman who was admitted to our hospital because of muscle weakness, bilateral shoulder pain, diffuse subcutaneous edema, and dysphagia that had gradually worsened during the past 5 months. Both patients showed severe diffuse subcutaneous edema and dysphagia and underwent enteral tube feeding. Although they had no skin lesions consistent with dermatomyositis, muscle biopsies showed myxovirus resistance protein A (MxA) expansion, and blood tests showed positivity for anti-nuclear matrix protein 2 (anti-NXP-2) antibody. Therefore, both presents were diagnosed with anti-NXP-2 antibody-positive dermatomyositis sine dermatitis (DMSD). Anti-NXP-2 antibody-positive dermatomyositis has been reported to be closely associated with DMSD, severe edema and dysphagia. Differential diagnosis for patients who develop myositis with severe subcutaneous edema and dysphagia should include anti-NXP-2 antibody-positive dermatomyositis, and it is important to consider measurement of anti-NXP-2 antibody.

Recurrent rhabdomyolysis in a patient with a history of rhabdomyolysis due to severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is a hemorrhagic fever syndrome that is endemic to East Asia. Here, we describe a case of rhabdomyolysis, thought to have been caused by pemafibrate (which was prescribed for hyperlipidemia) or bacterial infection, in a patient who had experienced SFTS-induced rhabdomyolysis 4 years ago. This case suggests that SFTS causes muscle degeneration and can lead to recurrent rhabdomyolysis as a long-term complication.

A Case of Oculopharyngeal Muscular Dystrophy Caused by a Novel PABPN1 c.34G > T (p.Gly12Trp) Point Mutation without Polyalanine Expansion.

Immediately after the initial methionine codon, the PABPN1 gene encodes a stretch of 10 alanines, 1 glycine, and 2 alanines. Oculopharyngeal muscular dystrophy (OPMD) is caused by the expansion of the first 10 alanine stretches. The only exception is the missense mutation of glycine at the 12th residue into alanine, which elongates the stretch to 13 alanines by connecting the first and second stretch with the addition of one alanine in between, indicating that the expansion or elongation of the alanine stretch results in OPMD. We report a 77-year-old man with the novel missense mutation c.34G > T (p.Gly12Trp) in PABPN1 gene whose clinicopathological findings were compatible with OPMD. He presented with slowly progressive bilateral ptosis, dysphagia, and symmetrical proximal dominant muscle weakness. Magnetic resonance imaging revealed selective fat replacement of the tongue, bilateral adductor magnus, and soleus muscles. Immunohistochemistry studies of the muscle biopsy sample revealed PABPN1-posibive aggregates in the myonuclei which have been reported to be specific to OPMD. This is the first OPMD case caused by neither the expansion nor the elongation of alanine stretch. The present case suggests that OPMD may be caused not only by triplet repeats but also by point mutations.

[A case of neurosyphilis presenting as sudden onset of limbic encephalitis].

A 52-year-old male was carried to hospital by ambulance, because of an abrupt abnormal behavior and impaired consciousness. Soon after the arrival, the patient started a generalized seizure. Although the seizure was stopped by Midazolam, amnesia were observed. With meningeal irritation signs, in addition to the clinical course, the patient was thought to develop limbic encephalitis. The cause of the encephalitis was diagnosed as neurosyphilis because of the positive serum and CSF syphilis reactions, and the patient was treated with penicillin G from the first admission day on. Steroid pulse therapy was also conducted, followed by acyclovir since herpes encephalitis could not be ruled out; the brain MRI showed left-side dominant T2/FLAIR high intensity lesions in the bilateral temporal lobes and left hippocampus. With the treatment progression, the amnestic syndrome improved and the patient returned to work. Although neurosyphilis is a rare cause of acute onset limbic encephalitis, it is important to keep the possibility of this disease in mind in making a treatment plan.

Cerebral syphilitic gumma mimicking a brain tumor that enlarged temporarily after commencing antibiotic treatment.

In this case report, we describe a 60-year-old man who presented with headaches for 1 year and mild confusion for 3 weeks and was initially diagnosed as having a cerebral tumor on the basis of finding a round lesion in the right lenticular nucleus with ring enhancement on gadolinium-enhanced T1-weighted brain magnetic resonance imaging. However, the discovery of positive serology for Treponema pallidum infection on routine tests on admission prompted analysis of cerebrospinal fluid, which was also positive on Treponema pallidum hemagglutination (TPHA), rapid plasma reagin (RPR), and treponemal antibody absorption (FTA-ABS) tests. Thus, he was diagnosed as having an intracranial syphilitic gumma. After commencing treatment with penicillin G, the lesion temporarily increased in size, but subsequently resolved completely with continuing antibiotic treatment. In the present era of increasing prevalence of syphilitic infection and because they are eminently treatable, syphilitic gummas should be included in the differential diagnosis of apparent brain tumors. Additionally, temporary enlargement of a probable gumma after instituting antibiotic treatment should not prompt cessation or change of the antibiotics.

Bromisoval-induced bromism with status epilepticus mimicking Wernicke's encephalopathy: report of two cases.

BACKGROUND: Bromine compounds are used in several drugs, including over-the-counter drugs. They sometimes cause intoxication known as bromism. Although the acute neurological symptoms and sequelae of bromism vary, few reports have mentioned acute encephalopathy. CASE PRESENTATION: We report two cases of bromisoval-induced bromism with status epilepticus. Presence of pseudohyperchloremia and history of over-the-counter medication use guided the diagnosis. In the acute phase, our patients showed bilateral medial thalamic lesions on magnetic resonance imaging. The imaging findings were similar to those of Wernicke's encephalopathy. Although these findings improved in the chronic phase, neuropsychiatric sequelae, such as confabulation and amnesia, occurred. CONCLUSION: Bromism can cause acute encephalopathy, and it is important to differentiate it from Wernicke-Korsakoff syndrome.

Anion gap-opening metabolic acidosis and urinary findings in the early diagnosis of ethylene glycol poisoning: A case report.

Causative agent identification is important in the treatment of poisoning. We report the case of a patient who presented with an altered level of consciousness after drinking a fluorescent pink liquid. Upon measuring the anion gap and urinary calcium oxalate level, the patient was diagnosed with early ethylene glycol poisoning.

The identified clinical features of Parkinson's disease in homo-, heterozygous and digenic variants of PINK1.

To investigate the prevalence and genotype-phenotype correlations of phosphatase and tensin homolog induced putative kinase 1 (PINK1) variants in Parkinson's disease (PD) patients, we analyzed 1700 patients (842 familial PD and 858 sporadic PD patients from Japanese origin). We screened the entire exon and exon-intron boundaries of PINK1 using Sanger sequencing and target sequencing by Ion torrent system. We identified 30 patients with heterozygous variants, 3 with homozygous variants, and 3 with digenic variants of PINK1-PRKN. Patients with homozygous variants presented a significantly younger age at onset than those with heterozygous variants. The allele frequency of heterozygous variants in patients with age at onset at 50 years and younger with familial PD and sporadic PD showed no differences. [123I]meta-iodobenzylguanidine (MIBG) myocardial scintigraphy indicated that half of patients harboring PINK1 heterozygous variants showed a decreased heart to mediastinum ratio (12/23). Our findings emphasize the importance of PINK1 variants for the onset of PD in patients with age at onset at 50 years and younger and the broad spectrum of clinical symptoms in patients with PINK1 variants.

A case of type 1 facioscapulohumeral muscular dystrophy (FSHD) with restrictive ventilatory defect and congestive heart failure.

[Background] Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscle disease characterized by asymmetric involvement of muscles in the face, upper extremity, trunk, and lower extremity regions, with variable severity. It was recently reported that restrictive respiratory involvement is more frequent and severe than previously recognized, while cardiac dysfunction other than arrhythmia is still considered extremely rare in FSHD. [Case report] A 59-year-old man presenting with marked muscle atrophy in the trunk and asymmetrical muscle atrophy in the legs was hospitalized because of dyspnea and edema in the face and limbs. Shortness of breath with body movement started from approximately 40 years of age. Muscle biopsy revealed myopathic change with mild to moderate variation in fiber size. The diagnosis of FSHD was made by D4Z4 contraction to three repeats on genetic testing. A pulmonary function test revealed a decline of forced vital capacity (FVC) and a preserved FEV1/FVC indicating restrictive ventilatory defect (RVD). Ultrasonic echocardiogram (UCG) showed diffuse left ventricular hypokinesis, ventricular septum thickening, pericardial effusion, and decreased ejection fraction (LVEF 30%). [Conclusion] Although restrictive ventilatory defect and congestive heart failure are uncommon in FSHD, respiratory and cardiac evaluation may be necessary in patients with FSHD.

Successful treatment with corticosteroids for refractory deterioration of cryptococcal meningitis with an increasing cryptococcal antigen titer.

We report a 55-year-old man with Cryptococcus neoformans meningitis who showed refractory deterioration twice with an increased cerebrospinal fluid cryptococcal antigen titer during the course of treatment. Although the initial deterioration was temporarily improved by placement of a ventriculoperitoneal shunt, he experienced deterioration again. However, he improved after administration of systemic corticosteroids. The present case suggests that systemic corticosteroid can be a choice of treatment to rescue immunocompetent patients with Cryptococcus neoformans meningitis and severe deterioration, even if cerebrospinal fluid analysis shows an increased cryptococcal antigen titer.

Unique HLA haplotype associations in IgG4 anti-neurofascin 155 antibody-positive chronic inflammatory demyelinating polyneuropathy.

To clarify the immunogenetic background of patients with immunoglobulin G (IgG)4 anti-neurofascin 155 (NF155) antibody-positive chronic inflammatory demyelinating polyneuropathy (CIDP), we genotyped the extended human leukocyte antigen (HLA) haplotypes in 22 Japanese patients with this disorder and compared them with those of healthy Japanese controls. All IgG4 anti-NF155 antibody-positive CIDP patients exclusively carried either HLA-DRB1*15:01-DRB5*01:01-DQA1*01:02-DQB1*06:02 or -(A*24:02)-B*52:01-C*12:02-DRB1*15:02-DRB5*01:02-DQA1*01:03-DQB1*06:01, resulting in significantly increased HLA-DRB1*15, -DRB1*15:01, -DQB1*06:01/06:02, -DQB1*06:02, and -DRB1*15:01-DQB1*06:02 frequencies compared with healthy Japanese controls. These findings indicate the involvement of specific HLA class II molecules in the pathomechanisms of IgG4 anti-NF155 antibody-positive CIDP.

Intrathecal cytokine profile in neuropathy with anti-neurofascin 155 antibody.

OBJECTIVE: To characterize the CSF cytokine profile in chronic inflammatory demyelinating polyneuropathy (CIDP) patients with IgG4 anti-neurofascin 155 (NF155) antibodies (NF155+ CIDP) or those lacking anti-NF155 antibodies (NF155- CIDP). METHODS: Twenty-eight CSF cytokines/chemokines/growth factors were measured by multiplexed fluorescent immunoassay in 35 patients with NF155+ CIDP, 36 with NF155- CIDP, and 28 with non-inflammatory neurological disease (NIND). RESULTS: CSF CXCL8/IL-8, IL-13, TNF-α, CCL11/eotaxin, CCL2/MCP-1, and IFN-γ were significantly higher, while IL-1ß, IL-1ra, and G-CSF were lower, in NF155+ CIDP than in NIND. Compared with NF155- CIDP, CXCL8/IL-8 and IL-13 were significantly higher, and IL-1ß, IL-1ra, and IL-6 were lower, in NF155+ CIDP. CXCL8/IL-8, IL-13, CCL11/eotaxin, CXCL10/IP-10, CCL3/MIP-1α, CCL4/MIP-1ß, and TNF-α levels were positively correlated with markedly elevated CSF protein, while IL-13, CCL11/eotaxin, and IL-17 levels were positively correlated with increased CSF cell counts. IL-13, CXCL8/IL-8, CCL4/MIP-1ß, CCL3/MIP-1α, and CCL5/RANTES were decreased by combined immunotherapies in nine NF155+ CIDP patients examined longitudinally. By contrast, NF155- CIDP had significantly increased IFN-γ compared with NIND, and exhibited positive correlations of IFN-γ, CXCL10/IP-10, and CXCL8/IL-8 with CSF protein. Canonical discriminant analysis of cytokines/chemokines revealed that NF155+ and NF155- CIDP were separable, and that IL-4, IL-10, and IL-13 were the three most significant discriminators. INTERPRETATION: Intrathecal upregulation of type 2 helper T (Th2) cell cytokines is characteristic of IgG4 NF155+ CIDP, while type 1 helper T cell cytokines are increased in CIDP regardless of the presence or absence of anti-NF155 antibodies, suggesting that overproduction of Th2 cell cytokines is unique to NF155+ CIDP.

Effect of intravenous immunoglobulin therapy on anti-NT5C1A antibody-positive inclusion body myositis after successful treatment of hepatitis C: A case report.

Inclusion body myositis (IBM) is the commonest idiopathic inflammatory myopathy of older persons. Pathophysiological mechanism of IBM remains unknown; however, an association of IBM with chronic hepatitis C virus (HCV) infection and serum autoantibodies against skeletal muscle protein 5'-nucleotidase 1A (NT5C1A) has recently been reported. No effective treatment for IBM has yet been developed. We here present a 70-year-old man who was anti-NT5C1A antibody-positive in association with IBM and chronic hepatitis C. The initial treatment of ombitasvir/paritaprevir/ritonavir for his chronic hepatitis C was successful; however, his symptoms of IBM did not improve. On the contrary, his quadriplegic paralysis became more severe and he developed dysphagia. Next, steroid pulse therapy was initiated for IBM and, although his hyper-creatine phosphokinase-emia improved, his symptoms did not; indeed, they worsened. Subsequent intravenous immunoglobulin therapy (IVIg) resulted in obvious improvement in his dysphagia. Thereafter IVIg therapy was repeated at approximately 2-monthly intervals. His dysphagia remained improved for more than 1 year; however, his quadriplegia continued to progress slowly. Although IBM can reportedly be associated with hepatitis C, we inferred that there was no direct relationship between these conditions in our patient because his IBM did not improve after treatment of his hepatitis C. Although his IBM-associated quadriplegia did not improve, IVIg therapy did result in improvement in his dysphagia.

Clinical Benefits of Antioxidative Supplement Twendee X for Mild Cognitive Impairment: A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Prospective Interventional Study.

Oxidative stress is part of the entire pathological process that underlies the development of Alzheimer's disease (AD), including the mild cognitive impairment (MCI) stage. Twendee X (TwX) is a supplement containing a strong antioxidative mix of eight antioxidants, which has been shown to have a clinical and therapeutic benefit in AD model mice. Here, we conducted a multicenter, randomized, double-blind, and placebo-controlled prospective interventional study to evaluate the efficacy of TwX in mitigating MCI. The primary outcomes were differences in Mini-Mental State Examination (MMSE) and Hasegawa Dementia Scale-revised (HDS-R) scores between baseline and six months for placebo and TwX groups. Seventy-eight subjects with MCI were randomized into placebo (n = 37) and TwX (n = 41) groups. MMSE scores at six months differed significantly between the TwX and placebo groups (p = 0.018), and HDS-R scores for the TwX group exhibited a significant improvement at six months relative to baseline (p = 0.025). The TwX group did not show any change in affective or activities of daily living scores at six months. The present study indicates that strong antioxidative supplement TwX is clinical beneficial for cognitive function in subjects with MCI.

A case of seropositive autoimmune autonomic ganglionopathy with diffuse esophageal spasm.

Autoimmune autonomic ganglionopathy (AAG) is an immune-mediated disorder that leads to various autonomic failures associated with anti-ganglionic acetylcholine receptor antibodies (anti-gAChR-Abs). Diffuse esophageal spasm (DES) is an uncommon esophageal motility disorder. We herein report the case of a 68-year-old woman with DES as a partial symptom of AAG. She presented with chronic esophageal transit failure, constipation, and numbness of the hands and feet, Adie's pupil, thermal hypoalgesia, and decreased deep tendon reflexes. Right sural nerve biopsy showed significantly decreased numbers of small myelinated fibers. Barium swallowing X-ray showed repetitive simultaneous contractions indicating DES in the esophagus. Gastrointestinal endoscopy and CT image showed a dilated esophageal lumen and liquid effusion. Simultaneously, serum anti-gAChR-α3-Ab indicating AAG was detected. After pulse intravenous methylprednisolone (IVMP) and intravenous immunoglobulin therapy (IVIg), the bolus progression and liquid effusion improved, suggesting that DES is an important gastrointestinal symptom of AAG.

A patient develops transient unique cerebral and cerebellar lesions after unruptured aneurysm coiling.

BACKGROUND: We describe a case of a very unusual complication following a coiling procedure in which the patient developed transient unique cerebral and cerebellar lesions. Lesions were examined not only by magnetic resonance imaging (MRI) but also by positron emission tomography-computed tomography (PET-CT) and proton magnetic resonance spectroscopy ((1)H-MRS). CASE PRESENTATION: A 33-year-old woman presented an incidental 3.7 × 3.3-mm unruptured cerebral aneurysm (CAn) in her basilar artery, which was successfully coiled with balloon assistance. A follow-up brain MRI at 1 and 2 months showed a gradual increase in several white matter hyperintense lesions in the left cerebellar, bilateral occipitotemporal and left parietoccipital lobe during fluid-attenuated inversion recovery (FLAIR). These were the only lesions associated with perfused CAn. However, the patient did not show any additional symptoms such as visual disturbance throughout the entire course. (11)C-methionine-PET (MET-PET) showed an obvious increase in methionine uptake in the lesion corresponding to enhanced areas with gadolinium-enhanced MRI. MRS showed a decrease in the N-acetylaspartate/creatine (NAA/cr) ratio and a slight elevation of the choline/creatine (cho/cr) ratio and a lactate peak in the lesion. A follow-up MRI at 6 and 12 months showed a gradual decrease in the initial hyperintense lesions in FLAIR without any treatment. CONCLUSION: We present a case of an unusual complication after a coiling procedure. Although it is difficult to identify this etiology without a pathological examination, it is importance to increase awareness of such a potential complication arising from coiling procedures, because interventional procedures have become the first choice of treatment for cerebrovascular diseases in many countries.

Long-term effect of telmisartan on Alzheimer's amyloid genesis in SHR-SR after tMCAO.

Telmisartan is expected to reduce not only the level of blood pressure but also neuroinflammation and neurotoxicity via pleiotrophic effects as a metabo-sartan. We examined the effects of telmisartan on Alzheimer's disease (AD) pathology in spontaneously hypertensive rat stroke resistant (SHR-SR) after transient middle cerebral artery occlusion (tMCAO) by giving either telmisartan at 0 (vehicle), 0.3 mg/kg/day (low dose, with no reduction of blood pressure), or 3 mg/kg/day (high dose, with a significant reduction of blood pressure) p.o. from 3 months (M) of age, and performed immunohistological analysis at 6, 12, and 18 M of age. The numbers of amyloid ß (Aß)-positive neurons in the cerebral cortex and hippocampus and senile plaque (SP) in the ipsilateral cerebral cortex progressively increased with age until 18 M in the SHR-SR after tMCAO. On the other hand, low-dose telmisartan significantly reduced the number of Aß-positive neuron as well as SP at 6, 12, and 18 M. High-dose telmisartan showed further reductions of the above AD pathology. The present study suggests that telmisartan reduced both intracellular Aß and extracellular SP accumulations after tMCAO in SHR-SR, with a further improvement by combined BP lowering. Such a strong effect of telmisartan could provide a preventative approach for AD in post-stroke patients with hypertension.

Telmisartan reduces progressive accumulation of cellular amyloid beta and phosphorylated tau with inflammatory responses in aged spontaneously hypertensive stroke resistant rat.

BACKGROUND: In addition to reducing the level of blood pressure (BP), telmisartan was expected to show the long-term neuroprotective effects preventing accumulation of cellular amyloid beta peptide (Aß) and phosphorylated tau (pτ) by ameliorating neuroinflammation. METHODS: We examined effects of telmisartan on cellular Aß and pτ with inflammatory responses in the brain of a spontaneously hypertensive stroke resistant (SHR-SR) rat by giving either telmisartan at 0 (vehicle), .3 mg/kg/day or 3 mg/kg/day, orally, from 3 months of age and performed immunohistologic analysis at 6, 12, and 18 months. Compared with normotensive Wistar rats, numbers of Aß- and pτ-positive neurons in the cerebral cortex progressively increased with age until 18 months in the SHR-SR rats, as did the numbers of ionized calcium-binding adapter molecule 1 (Iba-1)-positive microglia, tumor necrosis factor alpha (TNF-α)-positive neurons, and monocyte chemotactic protein 1 (MCP-1)-positive neurons. RESULTS: Low-dose telmisartan significantly decreased the numbers of Aß- and pτ-positive neuron as well as the numbers of TNF-α-positive neurons, Iba-1-positive microglia, and MCP-1-positive neurons at 6, 12, and 18 months. High-dose telmisartan reduced BP and showed a further reduction of cellular Aß and pτ. CONCLUSIONS: The present study suggests that accumulation of cellular Aß and pτ and the inflammatory responses were decreased via improving metabolic syndrome with low-dose telmisartan and improving both metabolic syndrome and hypertension with high-dose telmisartan.

Strong improvement of apolipoprotein E/low-density lipoprotein receptor signals by telmisartan in poststroke spontaneously hypertensive stroke resistant.

BACKGROUND: Telmisartan, an angiotensin receptor blocker also called metabosartan, is a promising solution for preventing cognitive decline or the incidence of dementia. METHODS: We examined the effects of telmisartan on cholesterol transport-related proteins (apolipoprotein E [ApoE]/low-density lipoprotein receptor [LDL-R]) and microtubule-associated protein 2 (MAP2) in the brain of spontaneously hypertensive stroke resistant (SHR-SR). SHR-SR received transient middle cerebral artery occlusion (tMCAO) for 90 minutes at 12 weeks of age and then was divided into 3 experiment groups including a vehicle, low-dose telmisartan (.3 mg/kg/day), and high-dose telmisartan (3 mg/kg/day). RESULTS: The low dose served to improve the metabolic syndrome of SHR-SR without lowering the blood pressure (BP) whereas the high dose was used to improve metabolic syndrome while lowering BP. Immunohistologic analysis showed that ApoE expression of cortical neurons was strong in the vehicle group at 6, 12, and 18 months of age, and that this ApoE expression pattern was very similar between the ipsilateral and contralateral sides of cerebral ischemia. On the other hand, LDL-R expression of cortical neurons was transiently increased at 6 months of age only on the ipsilateral side. Telmisartan dramatically suppressed the expression of ApoE/LDL-R at both doses. There was no remarkable difference in neuronal MAP2 staining between the 3 groups. CONCLUSIONS: These findings suggest that both low and high doses of telmisartan prevented the activation of ApoE/LDL-R in SHR-SR after tMCAO, and that the antimetabolic effect was regarded as the most important mechanism with few additional benefits by lowering BP in this transient stroke model.

Pulsion severity showed a good correlation with cognitive function in Parkinson's disease.

OBJECTIVES: To examine the correlation between cognitive impairment and postural instability in Parkinson's disease (PD) patients by using posturography. METHODS: We investigated 88 PD patients comparing clinical scorings of cognitive functions and pulsion severity, and quantitative measurement of postural instability by posturography with the length of the center of gravity (LNG) and envelope area (ENV). RESULTS: The number of patients with severe pulsion increased in PD with disease progression assessed by Hoehn and Yahr (H & Y) scale regardless of age, and a significant correlation was observed between the pulsion severity and both LNG (R  =  0.4242) and ENV (R  =  0.4335). Both LNG and ENV showed a good correlation with all cognitive assessments such as mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA), and frontal assessment battery (FAB), suggesting that cognitive impairment became worse with the longer LNG and the larger ENV. Among the cognitive assessments, MoCA showed the highest correlation (R  =  0.56-0.62) with both LNG and ENV, reflecting that MoCA is the most sensitive and reliable screening for dementia in PD. DISCUSSION: The present study showed that posturography is useful to quantify the pulsion severity in PD patients, that pulsion severity and cognitive function showed a good correlation especially assessed by MoCA, and that posturography thus provides a more detailed quantitative correlation of postural instability to cognitive impairment.