Exploring the fuzzy border between senolytics and senomorphics with chemoinformatics and systems pharmacology

Biogerontology - Senescent cells accumulate within tissues during aging and secrete an array of pro-inflammatory molecules known as senescent-associated secretory phenotype (SASP), which contribute...     

Analysis of nocturnal desaturation waveforms using algorithms in patients with idiopathic pulmonary fibrosis

Purpose

Sleep-disordered breathing is recognized as a comorbidity in patients with idiopathic pulmonary fibrosis (IPF). Among them, nocturnal hypoxemia has been reported to be associated with poor prognosis and disease progression. We developed a diagnostic algorithm to classify nocturnal desaturation from percutaneous oxygen saturation (SpO₂) waveform patterns: sustained pattern, periodic pattern, and intermittent pattern. We then investigated the prevalence of nocturnal desaturation and the association between the waveform patterns of nocturnal desaturation and clinical findings of patients with IPF.

Methods

We prospectively enrolled patients with IPF from seven general hospitals between April 2017 and March 2020 and measured nocturnal SpO₂ and nasal airflow by using a home sleep apnea test. An algorithm was used to classify the types of nocturnal desaturation. We evaluated the association between sleep or clinical parameters and each waveform pattern of nocturnal desaturation.

Results

Among 60 patients (47 men) who met the eligibility criteria, there were 3 cases with the sustained pattern, 49 cases with the periodic pattern, and 41 cases with the intermittent pattern. Lowest SpO₂ during sleep and total sleep time spent with SpO₂?<?90% were associated with the sustained pattern, and apnea–hypopnea index was associated with the intermittent pattern.

Conclusion

We demonstrated the prevalence of each waveform and association between each waveform and sleep parameters in patients with IPF. This classification algorithm may be useful to predict the degree of hypoxemia or the complication of obstructive sleep apnea.

     

Fractal correlation properties of R-R interval dynamics in asymptomatic relatives of patients with dilated cardiomyopathy

BACKGROUND AND AIM: asymptomatic relatives of patients with familial dilated cardiomyopathy who have left ventricular enlargement [LVE] are at risk for progression to dilated cardiomyopathy. A novel index of the fractal correlation properties of heart rate variability (HRV), the short-term scaling component (proportional, variant(1)) in detrended fluctuation analysis, is a promising prognostic tool in left ventricular dysfunction. The aim of this study was to compare values of proportional, variant(1) and conventional HRV indices in LVE relatives with dilated cardiomyopathy patients and normal controls. METHODS: time-domain and spectral HRV measures, and the short-term scaling component ( proportional, variant(1)) were assessed from 24-h Holter recordings from 22 LVE relatives (left ventricular end-diastolic dimension >112% predicted, normal fractional shortening), 24 dilated cardiomyopathy patients and 14 controls. RESULTS: the time domain index SDNN was lower in dilated cardiomyopathy patients [101.8(+/-44.0)] than in LVE relatives [161.7(+/-53.9)] or controls [152.9(+/-51.4)], P=0.01. Similarly, triangular index and spectral measures were reduced in dilated cardiomyopathy patients but not in LVE relatives or controls. In contrast, the short term scaling component ( proportional, variant(1)) in detrended fluctuation analysis was reduced in both dilated cardiomyopathy patients [1.06(+/-0.33)] and in LVE relatives [1.15 (+/-0.20)], compared with controls [1.32(+/-0.16)], P=0.01. Among DCM patients the short-term scaling component ( proportional, variant(1)) was significantly associated with echocardiographic deterioration during follow-up (3.7+/-2.1 year) (P=0.004). CONCLUSION: the short-term scaling component ( proportional, variant(1)) is reduced in asymptomatic relatives of dilated cardiomyopathy patients who have LVE.     

Vitamins, supplements, herbal medicines, and arrhythmias

Nutritional and herbal supplements may have harmful or beneficial effects on arrhythmias. Potential supplements that may have antiarrhythmic activity include omega-3 polyunsaturated fatty acids (N-3 PUFA), coenzyme Q10, and carnitine. Clinical studies show that N-3 PUFA or fish oil supplementation appears to reduce mortality and sudden death. Coenzyme Q10, used in treatment of heart failure, and carnitine and its derivatives may have beneficial effects on arrhythmias, although clinical studies have been limited. Antioxidant supplements may be beneficial, but large studies with vitamin E have been disappointing in that it does not reduce mortality. Correction of electrolyte disturbances has been long advised and magnesium supplementation has been beneficial in the treatment of torsades de pointes and in some studies after cardiac surgery. However, routine electrolyte supplementation with empiric potassium or magnesium in non-deficient patients has not been convincingly beneficial. Several herbal supplements have also been promoted to have antiarrhythmic activity. However, clinical studies are lacking to support routine use of these herbal medications. In addition, some herbal supplements may cause serious proarrhythmia, and many supplements significantly interact with warfarin and digoxin.     

Reversible respiratory failure due to rhabdomyolysis associated with cytomegalovirus infection

A 58-year-old woman presented with muscle weakness, whole body myalgia, and dyspnea. On admission, neurological examination showed proximal muscle weakness in the extremities. The weakness gradually extended to the bulbar and respiratory muscles, necessitating an artificial ventilator. Serum CK level was markedly increased (33,774 IU/L; normal <150 IU/L) and myoglobinuria was noted in urinalysis. There was no sign of renal failure. Nerve conduction study was normal, but needle EMG showed myopathic changes in the weak muscles. Serological studies for virus titers showed more than a four-fold increase of cytomegalovirus (CMV) antibody titer during the disease course. The IgM anti-GM2 antibody was also elevated in the acute phase and decreased in the recovery phase. The muscle weakness and respiratory failure gradually improved after intravenous methylprednisolone administration, and the serum CK level was normalized in several days. CMV infection was thought to have played a central role in the rhabdomyolysis, leading to critical but reversible respiratory muscle paralysis.