Bioactivities and mechanisms of natural medicines in the management of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a progressive and rare disease without obvious clinical symptoms that shares characteristics with pulmonary vascular remodeling. Right heart failure in the terminal phase of PAH seriously threatens the lives of patients. This review attempts to comprehensively outline the current state of knowledge on PAH its pathology, pathogenesis, natural medicines therapy, mechanisms and clinical studies to provide potential treatment strategies. Although PAH and pulmonary hypertension have similar pathological features, PAH exhibits significantly elevated pulmonary vascular resistance caused by vascular stenosis and occlusion. Currently, the pathogenesis of PAH is thought to involve multiple factors, primarily including genetic/epigenetic factors, vascular cellular dysregulation, metabolic dysfunction, even inflammation and immunization. Yet many issues regarding PAH need to be clarified, such as the “oestrogen paradox”. About 25 kinds monomers derived from natural medicine have been verified to protect against to PAH via modulating BMPR2/Smad, HIF-1α, PI3K/Akt/mTOR and eNOS/NO/cGMP signalling pathways. Yet limited and single PAH animal models may not corroborate the efficacy of natural medicines, and those natural compounds how to regulate crucial genes, proteins and even microRNA and lncRNA still need to put great attention. Additionally, pharmacokinetic studies and safety evaluation of natural medicines for the treatment of PAH should be undertaken in future studies. Meanwhile, methods for validating the efficacy of natural drugs in multiple PAH animal models and precise clinical design are also urgently needed to promote advances in PAH. Graphical Abstract

Caregivers’ View of Socio-Medical Care in the Terminal Phase of Amyotrophic Lateral Sclerosis—How Can We Improve Holistic Care in ALS?

Multidimensional socio-medical care with an early integration of palliative principles is strongly recommended in amyotrophic lateral sclerosis (ALS), but provided inconsistently. We conducted telephone interviews with 49 former caregivers of deceased ALS patients to examine their experience of care in the terminal phase including caregiver burden. Patients who received specialized palliative care (45% of patients) were more likely to die at home (p = 0.004) and without burdening symptoms (p = 0.021). The majority of caregivers (86%) reported deficits in socio-medical care. Most frequently mentioned were problems receiving medical aids (45%) and a lack of caregiver support (35%). A higher level of deficits experienced by caregivers was associated with negative health outcomes on the side of the caregivers (reported by 57% of them; p = 0.002) and stronger caregiver burden (p = 0.004). To provide good quality of dying to patients and reduce the burden on caregivers, multidimensional—including palliative—care in ALS urgently needs to be strengthened in the healthcare structures.

Maintainability of electronic instruments for meteorological applications

The concept of Maintainability (M) of electronic instruments. though of recent origin, has Important application for meteorological equipments, which have special requirements. M is defined quantitatively in terms of mean time to repair and is Influenced by the failure behaviour of an equipment. An equipment goes through teething trouble, useful and terminal phase. Much of maintainability can be incorporated during design and production phase. This reduces the effective overall cost of the equipment during its life time. Special maintenance support system is necessary for meteorological Instruments. Some recent tools for trouble shooting in digital systems have been discussed.

Degenerative disc disease in young adults: cytokine profile and angiogenic factors

Back pain (BP), associated with the degenerative disc disease (DDD), poses a heavy social and economic burden due to early disability and indications to surgery, emerging in young adults. Pathophysiological basis of premature intervertebral disc (IVD) degeneration is being actively studied. The study was aimed to define the profiles of inflammatory cytokines in DDD, as well as their relationship to the structural spine diseases. The molecular genetic analysis of the mRNA gene abundance in patients with BP and herniated IVD after discectomy and healthy individuals was performed by the quantitative polymerase chain reaction method. High expression of TNFα, IL17 was revealed in the IVD tissues of the affected patients (p < 0.01); the levels of TNFα and IL1β correlated with the DDD severity (r = 0.301 and 0.37; p < 0.05). Elevated expression of IL1β, IL6 was found in peripheral white blood cells (p < 0.01); the levels of IL6 negatively correlated with Modic type 1 and 2 changes (r = –0.31; p < 0.05), and the levels of IL17 positively correlated with the IVD herniation in combination with erosions of the adjacent vertebral body endplates and Modic changes (r = 0.401; p < 0.05). The expression of VEGF-А in the IVD tissues and white blood cells negatively correlated with the DDD grades (r = –0.85; p < 0.001), indicating reduced vascularization in the terminal phase of the disease. The findings on DDD demonstrate the contribution of the local low-immune inflammation, coupled with the intense disc vascularization at the earlier stages, and associated with the reactive inflammation in vertebral bodies. The results are prerequisites for developing the anti-inflammatory and reparative therapy based on the DDD grade and the presence of Modic changes in young adults with BP.

CMAC Trained Optimum Mid course Guidance for Tactical Flight Vehicle

This paper discusses design and validation of neural network based mid-course guidance law of a surface to air flight vehicle. In present study, initially different optimal trajectories have been generated off-line of different pursuer-evader engagements by ensuring minimum flight time, maximum terminal velocity and favorable handing over conditions for seeker based terminal guidance. These optimal trajectories have been evolved by nonlinear programming based direct method of optimisation. The kinematic information of both pursuer and evader, generated based on these trajectories have been used to train cerebellar model articulate controller (CMAC) neural network. Later for a given engagement scenario an on-line near optimal mid-course guidance law has been evolved based on output of trained network. Training has been carried out by CMAC type supervisory neural network. The tested engagement condition is within input/output training space of neural network. Seeker based homing guidance has been used for terminal phase. Complete methodology has been validated along pitch plane of pursuer-evader engagement. During mid-course phase, the guidance demand has been tracked by attitude hold autopilot and during terminal phase, the guidance demanded lateral acceleration has been tracked by acceleration autopilot. System robustness has been studied in presence of plant parameter variations and sensor noise under Monte Carlo Platform.

Factors Influencing Decision-Making of Terminally Ill Cancer Patients and Their Families Regarding Where to Stay and Receive Final-Month Care: A Preliminary Study

Background:Advance care planning is essential for a better terminal phase, although many patients do not make a choice regarding the place of receiving terminal care even one month before the expected end of life. This study explores the factors that influence patients with a life-expectancy of less than one month when they are admitted to the palliative care ward or other terminal care institutions.Methods: Self-administered questionnaire surveys were completed by patients and caregiver questionnaire surveys were completed by patients and caregivers. We assessed patient symptoms using Support Team Assessment Schedule-Japan (STAS-J), and all patients’ families answered the self-reported questionnaire, Caregiver Reaction Assessment-Japan (CRA-J).Results: The family care burden score for “Impact on schedule” was significantly higher for the palliative care ward inpatient group than for the non-inpatient group (21.0±1.5 vs. 17.6±1.8; ρ <0.01).Conclusions: Family burden might influence the choice of facility when patients with a survival prognosis of less than one month are admitted to the palliative care ward for reducing the burden of long-term care. Nurses should take care of family caregiver’s physical and psychosocial health, especially before the patient’s admission to the palliative care ward. The results of this study show that caregiver support is needed to reduce the feeling of family burden related to impact on schedule, enabling them to choose the best place for terminal care.

Management of the actively dying patient

Few issues so encapsulate the palliative care as the skilled care of the dying patient and their family members. How patients die is a matter of supreme consequence in the human life cycle and for the surviving family. This chapter presents a multidisciplinary approach to highlighting challenges in identifying the terminal phase, approaches to help the clinician address the needs of patients and their family members, the management of common symptoms at the end of life including the management of refectory symptoms at the end of life. Tabulated information highlights some of the special issues including practical ways family members can participle in the care of their loved ones. The chapter concludes with some of the challenging issues related to hydration and nutrition, difficult deaths and staff coping and support.

Non-contact heart rate variability monitoring using Doppler radars located beneath bed mattress: a case report

Background Heart rate variability (HRV) has been investigated previously in autonomic nervous system-related clinical settings. In these settings, HRV is determined by the time-series heartbeat peak-to-peak intervals using electrocardiography (ECG). To reduce patient discomfort, we designed a Doppler radar-based autonomic nervous activity monitoring system (ANMS) that allows cardiopulmonary monitoring without using ECG electrodes or spirometry monitoring. Case summary Using our non-contact ANMS, we observed a bedridden 80-year-old female patient with terminal phase sepsis developed the daytime Cheyne-Stokes respiration (CSR) associated with the attenuation of the low frequency (LF) and high frequency (HF) of HRV components 20 days prior to her death. The patient developed a marked linear decrease in the LF and the HF of HRV components for over 3 days in a row. Furthermore, after the decrease both the LF and the HF showed low and linear values. Around the intersection of the two lines, the decreasing LF and HF lines and the constant LF and HF lines, the ANMS automatically detected the daytime CSR pathogenesis. The attenuation rate of HF (1340 ms2/day) was higher than that of LF (956 ms2/day). Heart rate increased by ∼10 b.p.m. during these 3 days. Discussion We detected CSR-associated LF and HF attenuation in a patient with terminal phase sepsis using our ANMS. The proposed system without lead appears promising for future applications in clinical settings, such as remote cardiac monitoring of patients with heart failure at home or in long-term acute care facilities.