The impact of 2 years of high‐intensity exercise training on a model of integrated cardiovascular regulation

Key points Heart rate variability, a common and easily measured index of cardiovascular dynamics, is the output variable of complicated cardiovascular and respiratory control systems. Both neural and non‐neural control mechanisms may contribute to changes in heart rate variability. We previously developed an innovative method using transfer function analysis to assess the effect of prolonged exercise training on integrated cardiovascular regulation. In the present study, we modified and applied this to investigate the effect of 2 years of high‐intensity training on circulatory components to tease out the primary effects of training. Our method incorporated the dynamic Starling mechanism, dynamic arterial elastance and arterial–cardiac baroreflex function. The dynamic Starling mechanism gain and arterial–cardiac baroreflex gain were significantly increased in the exercise group. These parameters remained unchanged in the controls. Conversely, neither group experienced a change in dynamic arterial elastance. The integrated cardiovascular regulation gain in the exercise group was 1.34‐fold larger than that in the control group after the intervention. In these previously sedentary, otherwise healthy, middle‐aged adults, 2 years of high‐intensity exercise training improved integrated cardiovascular regulation by enhancing the dynamic Starling mechanism and arterial–cardiac baroreflex sensitivity.Abstract Assessing the effects of exercise training on cardiovascular variability is challenging because of the complexity of multiple mechanisms. In a prospective, parallel‐group, randomized controlled study, we examined the effect of 2 years of high‐intensity exercise training on integrated cardiovascular function, which incorporates the dynamic Starling mechanism, dynamic arterial elastance and arterial–cardiac baroreflex function. Sixty‐one healthy participants (48% male, aged 53 years, range 52–54 years) were randomized to either 2 years of exercise training (exercise group: n  = 34) or control/yoga group (controls: n  = 27). Before and after 2 years, subjects underwent a 6 min recording of beat‐by‐beat pulmonary artery diastolic pressure (PAD), stroke volume index (SV index), systolic blood pressure (sBP) and RR interval measurements with controlled respiration at 0.2 Hz. The dynamic Starling mechanism, dynamic arterial elastance and arterial–cardiac baroreflex function were calculated by transfer function gain between PAD and SV index; SV index and sBP; and sBP and RR interval, respectively. Fifty‐three participants (controls: n  = 25; exercise group: n  = 28) completed the intervention. After 2 years, the dynamic Starling mechanism gain (Group × Time interaction: P  = 0.008) and the arterial–cardiac baroreflex gain ( P  = 0.005) were significantly increased in the exercise group but remained unchanged in the controls. There was no change in dynamic arterial elastance in either of the two groups. The integrated cardiovascular function gain in the exercise group increased 1.34‐fold, whereas there was no change in the controls ( P  = 0.02). In these previously sedentary, otherwise healthy middle‐aged adults, a 2 year programme of high‐intensity exercise training improved integrated cardiovascular regulation by enhancing the dynamic Starling mechanism and arterial–cardiac baroreflex sensitivity, without changing dynamic arterial elastance.

APOBEC mutation drives early-onset squamous cell carcinomas in recessive dystrophic epidermolysis bullosa

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin and mucous membrane fragility disorder complicated by early-onset, highly malignant cutaneous squamous cell carcinomas (SCCs). The molecular etiology of RDEB SCC, which arises at sites of sustained tissue damage, is unknown. We performed detailed molecular analysis using whole-exome, whole-genome, and RNA sequencing of 27 RDEB SCC tumors, including multiple tumors from the same patient and multiple regions from five individual tumors. We report that driver mutations were shared with spontaneous, ultraviolet (UV) light-induced cutaneous SCC (UV SCC) and head and neck SCC (HNSCC) and did not explain the early presentation or aggressive nature of RDEB SCC. Instead, endogenous mutation processes associated with apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) deaminases dominated RDEB SCC. APOBEC mutation signatures were enhanced throughout RDEB SCC tumor evolution, relative to spontaneous UV SCC and HNSCC mutation profiles. Sixty-seven percent of RDEB SCC driver mutations was found to emerge as a result of APOBEC and other endogenous mutational processes previously associated with age, potentially explaining a >1000-fold increased incidence and the early onset of these SCCs. Human papillomavirus-negative basal and mesenchymal subtypes of HNSCC harbored enhanced APOBEC mutational signatures and transcriptomes similar to those of RDEB SCC, suggesting that APOBEC deaminases drive other subtypes of SCC. Collectively, these data establish specific mutagenic mechanisms associated with chronic tissue damage. Our findings reveal a cause for cancers arising at sites of persistent inflammation and identify potential therapeutic avenues to treat RDEB SCC.

Draft Genome Sequences of Escherichia coli Isolates from India

Escherichia coli causes diarrhea and extraintestinal infections in humans and animals. Here, we report the draft genome sequences of Escherichia coli strains 360/16 and 646, isolated from neonatal calves.

Metagenomic Exploration of Microbial Signatures on Periyar River Sediments from the Periyar Tiger Reserve in the Western Ghats

We report here targeted deep-sequencing metagenomic data that reveal a high level of diversity in the microbiota residing in the sediment of the Periyar River in a reserve forest of the Western Ghats. Of the 4,674 operational taxonomic units discovered, the dominant phyla represented were Proteobacteria (33.12%), Actinobacteria (14.58%), Acidobacteria (12.81%), and Bacteroidetes (9.89%).

Metagenomics Study of Contaminated Sediments from the Yamuna River at Kalindi Kunj, Delhi, India

The Yamuna River is the backbone of domestic, irrigation, and industrial activities in Delhi, India, yet the complex dynamics of its microbes and their contribution to biogeochemical cycles in a polluted environment remain elusive. This is an introductory report describing the microbial community in the Yamuna River, using high-throughput metagenomics.

G301 Cerebral venous thrombosis in childhood tuberculous meningitis

G302 Comparison of 4-weeks versus 12-weeks anti-convulsant therapy for acute symptomatic seizures in children with acute encephalitis syndrome- an open-label, randomised controlled trial

Cardiac tamponade causing severe reversible hyponatraemia

Severe hyponatraemia in setting of cardiac tamponade is very rare and only few case reports have been reported so far. This case report highlights pericardial tamponade as a rare but easily treatable cause of severe hyponatraemia. Pertinent literature is also reviewed. A 70-year-old woman presented to the emergency department with altered mental status. She was tachycardic and hypotensive with cardiomegaly on a chest X-ray. Serum sodium was severely low at 109 mmol/L and was identified as the likely cause for her abnormal mentation. She was also in acute renal failure with serum creatinine of 4.1 mg/dL. A transthoracic echocardiogram was done that showed a large pericardial effusion with evidence of tamponade physiology. She underwent emergent pericardiocentesis with rapid improvement in clinical picture and blood pressure. Her serum sodium level rapidly improved and was normal in 48 hours.

Association of giant retinal tear with iridofundal coloboma in a case of paediatric retinal detachment

Neuroleptic malignant-like syndrome causing thrombocytopaenia: a rare association

Neuroleptic malignant-like syndrome is a rare but potentially fatal complication of sudden withdrawal of dopaminergic drugs. Clinical features are similar to that of neuroleptic malignant syndrome (NMS) like hyperthermia, autonomic dysfunction, altered sensorium, muscle rigidity; but instead of history of neuroleptic use, there is history of withdrawal of dopaminergic drugs. Laboratory examination generally show elevated creatine phosphokinase levels and may show elevated total leucocyte count. Thrombocytopaenia has been very rarely reported with NMS but it has not been reported with NM-like syndrome. Here, we discuss a case of Parkinson’s disease which presented with typical clinical features and risk factors of NM-like syndrome associated with thrombocytopaenia and type 1 respiratory failure. He was treated with bromocriptine and supportive care. Thrombocytopaenia and respiratory failure resolved with above treatment. The patient improved clinically and was successfully discharged on day 12 of admission.