Utilisation of priority traditional medicinal plants and local people's knowledge on their conservation status in arid lands of Kenya (Mwingi District)

Mwingi District lies within the Kenyan Arid and Semiarid lands (ASALs) in Eastern Province. Although some ethnobotanical surveys have been undertaken in some arid and semiarid areas of Kenya, limited studies have documented priority medicinal plants as well as local people's awareness of conservation needs of these plants. This study sought to establish the priority traditional medicinal plants used for human, livestock healthcare, and those used for protecting stored grains against pest infestation in Mwingi district. Further, the status of knowledge among the local people on the threat and conservation status of important medicinal species was documented. This study identified 18 species which were regarded as priority traditional medicinal plants for human health. In terms of priority, 8 were classified as moderate, 6 high, while 4 were ranked highest priority species. These four species are Albizia amara (Roxb.) Boiv. (Mimosacaeae), Aloe secundiflora (Engl. (Aloaceae), Acalypha fruticosa Forssk. (Euphorbiaceae) and Salvadora persica L. (Salvadoraceae)

HIIT produces increases in muscle power and free testosterone in male masters athletes

High intensity interval training (HIIT) improves peak power output (PPO) in sedentary aging men but has not been examined in masters endurance athletes. Therefore, we investigated whether a 6-week programme of low volume HIIT would (i) improve PPO in masters athletes and (ii) whether any change in PPO would be associated with steroid hormone perturbations.Seventeen male masters athletes (60 ± 5 years) completed the intervention which comprised of nine HIIT sessions over six weeks. HIIT sessions involved six 30 s sprints at 40% PPO, interspersed with 3 min active recovery. Absolute PPO (799 ± 205 W and 865 ± 211 W) and relative PPO (10.2 ± 2.0 W·kg-1 and 11.0 ± 2.2 W·kg-1) increased from pre- to post-HIIT respectively (P<0.001, Cohen’s d=0.32-0.38). No significant change was observed for total testosterone (15.2 ± 4.2 nmol·l-1 to 16.4 ± 3.3 nmol·l-1 [P=0.061, Cohen’s d=0.32]), whilst a small increase in free testosterone occurred following HIIT (7.0 ± 1.2 ng·dl-1 to 7.5 ± 1.1 ng·dl-1 pre- to post-HIIT [P=0.050, Cohen’s d=0.40]). Six weeks’ HIIT improves PPO in masters athletes and increases free testosterone. Taken together, these data indicate there is a place for carefully timed HIIT epochs in regimes of masters athletes

High-intensity interval training (HIIT) increases insulin-like growth factor-I (IGF-I) in sedentary aging men but not masters’ athletes: an observational study

Introduction: The aim of this investigation was to examine the impact high-intensity interval training (HIIT) on serum insulin-like growth factor-I (IGF-I) in active compared with sedentary aging men. Methods: 22 lifetime sedentary (SED; 62 ± 2 years) and 17 masters’ athletes (LEX; 60 ± 5 years) were recruited to the study. As HIIT requires preconditioning exercise in sedentary cohorts, the study required three assessment phases; enrollment (phase A), following preconditioning exercise (phase B), and post-HIIT (phase C). Serum IGF-I was determined by electrochemiluminescent immunoassay. Results: IGF-I was higher in LEX compared to SED at baseline (p = 0.007, Cohen’s d = 0.91), and phase B (p = 0.083, Cohen’s d = 0.59), with only a small difference at C (p = 0.291, Cohen’s d = 0.35). SED experienced a small increase in IGF-I following preconditioning from 13.1 ± 4.7 to 14.2 ± 6.0 μg·dl−1 (p = 0.376, Cohen’s d = 0.22), followed by a larger increase post-HIIT (16.9 ± 4.4 μg·dl−1), which was significantly elevated compared with baseline (p = 0.002, Cohen’s d = 0.85), and post-preconditioning (p = 0.005, Cohen’s d = 0.51). LEX experienced a trivial changes in IGF-I from A to B (18.2 ± 6.4 to 17.2 ± 3.7 μg·dl−1 [p = 0.538, Cohen’s d = 0.19]), and a small change post-HIIT (18.4 ± 4.1 μg·dl−1 [p = 0.283, Cohen’s d = 0.31]). Small increases were observed in fat-free mass in both groups following HIIT (p < 0.05, Cohen’s d = 0.32–0.45). Conclusions: In conclusion, HIIT with preconditioning exercise abrogates the age associated difference in IGF-I between SED and LEX, and induces small improvements in fat-free mass in both SED and LEX

Short-term and lifelong exercise training lowers inflammatory mediators in older men

Increased basal low-grade inflammation is observed with advancing age, which is augmented by physical inactivity. However, data regarding the influence of lifelong exercise training and particularly high-intensity interval training (HIIT) on inflammatory mediators in older men are scarce. Therefore, we examined effects of 6weeks of aerobic preconditioning followed by 6weeks of HIIT on inflammatory mediators [interleukin (IL)-6, homocysteine, and high-sensitivity C-reactive protein (hsCRP)] in previously sedentary older men (SED) and masters athletes (LEX). Further, we investigated whether SED exhibited greater basal inflammatory biomarkers compared to LEX. Twenty-two men (aged 62±2years) participated in the SED group, while 17 age-matched LEX men (aged 60±5years) also participated as a positive comparison group. In SED, preconditioning (P=0.030, d=0.34) and HIIT (P=0.030, d=0.48) caused a reduction in IL-6 compared to enrollment. SED homocysteine did not change throughout (P>0.57; d0.42; d0.72), but homocysteine was not different (all P >0.131; d<0.41). Results of this study suggest moderate-intensity aerobic exercise and HIIT lowers IL-6 (and possible hsCRP) in previously sedentary older men. Moreover, lifelong exercise is associated with reduced concentrations of some inflammatory biomarkers in older males, and therefore, physical activity, rather than age per se, is implicated in chronic low-grade inflammation. Moreover, physical inactivity-induced inflammation may be partly salvaged by short-term exercise training

Deregulation of HDAC5 by Viral Interferon Regulatory Factor 3 Plays an Essential Role in Kaposi's Sarcoma-Associated Herpesvirus-Induced Lymphangiogenesis.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent for Kaposi's sarcoma (KS), which is one of the most common HIV-associated neoplasms. The endothelium is the thin layer of squamous cells where vascular blood endothelial cells (BECs) line the interior surface of blood vessels and lymphatic endothelial cells (LECs) are in direct contact with lymphatic vessels. The KS lesions contain a prominent compartment of neoplastic spindle morphology cells that are closely related to LECs. Furthermore, while KSHV can infect both LECs and BECs in vitro, its infection activates genetic programming related to lymphatic endothelial cell fate, suggesting that lymphangiogenic pathways are involved in KSHV infection and malignancy. Here, we report for the first time that viral interferon regulatory factor 3 (vIRF3) is readily detected in over 40% of KS lesions and that vIRF3 functions as a proangiogenic factor, inducing hypersprouting formation and abnormal growth in a LEC-specific manner. Mass spectrometry analysis revealed that vIRF3 interacted with histone deacetylase 5 (HDAC5), which is a signal-responsive regulator for vascular homeostasis. This interaction blocked the phosphorylation-dependent cytosolic translocation of HDAC5 and ultimately altered global gene expression in LECs but not in BECs. Consequently, vIRF3 robustly induced spindle morphology and hypersprouting formation of LECs but not BECs. Finally, KSHV infection led to the hypersprouting formation of LECs, whereas infection with a ΔvIRF3 mutant did not do so. Collectively, our data indicate that vIRF3 alters global gene expression and induces a hypersprouting formation in an HDAC5-binding-dependent and LEC-specific manner, ultimately contributing to KSHV-associated pathogenesis.IMPORTANCE Several lines of evidences indicate that KSHV infection of LECs induces pathological lymphangiogenesis and that the results resemble KS-like spindle morphology. However, the underlying molecular mechanism remains unclear. Here, we demonstrated that KSHV vIRF3 is readily detected in over 40% of various KS lesions and functions as a potent prolymphangiogenic factor by blocking the phosphorylation-dependent cytosolic translocation of HDAC5, which in turn modulates global gene expression in LECs. Consequently, vIRF3-HDAC5 interaction contributes to virus-induced lymphangiogenesis. The results of this study suggest that KSHV vIRF3 plays a crucial role in KSHV-induced malignancy

HDAC6 Inhibition Reverses Cisplatin-Induced Mechanical Hypersensitivity via Tonic Delta Opioid Receptor Signaling

Peripheral neuropathic pain induced by the chemotherapeutic cisplatin can persist for months to years after treatment. Histone deacetylase 6 (HDAC6) inhibitors have therapeutic potential for cisplatin-induced neuropathic pain since they persistently reverse mechanical hypersensitivity and spontaneous pain in rodent models. Here, we investigated the mechanisms underlying reversal of mechanical hypersensitivity in male and female mice by a 2 week treatment with an HDAC6 inhibitor, administered 3 d after the last dose of cisplatin. Mechanical hypersensitivity in animals of both sexes treated with the HDAC6 inhibitor was temporarily reinstated by a single injection of the neutral opioid receptor antagonist 6β-naltrexol or the peripherally restricted opioid receptor antagonist naloxone methiodide. These results suggest that tonic peripheral opioid ligand-receptor signaling mediates reversal of cisplatin-induced mechanical hypersensitivity after treatment with an HDAC6 inhibitor. Pointing to a specific role for δ opioid receptors (DORs), Oprd1 expression was decreased in DRG neurons following cisplatin administration, but normalized after treatment with an HDAC6 inhibitor. Mechanical hypersensitivity was temporarily reinstated in both sexes by a single injection of the DOR antagonist naltrindole. Consistently, HDAC6 inhibition failed to reverse cisplatin-induced hypersensitivity when DORs were genetically deleted from advillin+ neurons. Mechanical hypersensitivity was also temporarily reinstated in both sexes by a single injection of a neutralizing antibody against the DOR ligand met-enkephalin. In conclusion, we reveal that treatment with an HDAC6 inhibitor induces tonic enkephalin-DOR signaling in peripheral sensory neurons to suppress mechanical hypersensitivity

The F Plasmid Conjutome: The Repertoire of E coli Proteins Translocated Through an F-Encoded Type IV Secretion System

Bacterial conjugation systems pose a major threat to human health through their widespread dissemination of mobile genetic elements (MGEs) carrying cargoes of antibiotic resistance genes. Using the Cre Recombinase Assay for Translocation (CRAfT), we recently reported that the IncFV pED208 conjugation system also translocates at least 16 plasmid-encoded proteins to recipient bacteria. Here, we deployed a high-throughput CRAfT screen to identify the repertoire of chromosomally encoded protein substrates of the pED208 system. We identified 32 substrates encoded by the Escherichia coli W3110 genome with functions associated with (i) DNA/nucleotide metabolism, (ii) stress tolerance/physiology, (iii) transcriptional regulation, or (iv) toxin inhibition. The respective gene deletions did not impact pED208 transfer proficiencies, nor did Group 1 (DNA/nucleotide metabolism) mutations detectably alter the SOS response elicited in new transconjugants upon acquisition of pED208. However, MC4100(pED208) donor cells intrinsically exhibit significantly higher SOS activation than plasmid-free MC4100 cells, and this plasmid carriage-induced stress response is further elevated in donor cells deleted of several Group 1 genes. Among 10 characterized substrates, we gained evidence of C-terminal or internal translocation signals that could function independently or synergistically for optimal protein transfer. Remarkably, nearly all tested proteins were also translocated through the IncN pKM101 and IncP RP4 conjugation systems. This repertoire of E. coli protein substrates, here termed the F plasmid conjutome, is thus characterized by functions of potential benefit to new transconjugants, diverse TSs, and the capacity for promiscuous transfer through heterologous conjugation systems. Importance: Conjugation systems comprise a major subfamily of the type IV secretion systems (T4SSs) and are the progenitors of a second large T4SS subfamily dedicated to translocation of protein effectors. This study examined the capacity of conjugation machines to function as protein translocators. Using a high-throughput reporter screen, we determined that 32 chromosomally encoded proteins are delivered through an F plasmid conjugation system. The translocated proteins potentially enhance the establishment of the co-transferred F plasmid or mitigate mating-induced stresses. Translocation signals located C-terminally or internally conferred substrate recognition by the F system and, remarkably, many substrates also were translocated through heterologous conjugation systems. Our findings highlight the plasticity of conjugation systems in their capacities to co-translocate DNA and many protein substrates

Qualitative assessment of attitudes and knowledge on preterm birth in Malawi and within country framework of care

BACKGROUND: The overarching goal of this study was to qualitatively assess baseline knowledge and perceptions regarding preterm birth (PTB) and oral health in an at-risk, low resource setting surrounding Lilongwe, Malawi. The aims were to determine what is understood regarding normal length of gestation and how gestational age is estimated, to identify common language for preterm birth, and to assess what is understood as options for PTB management. As prior qualitative research had largely focused on patient or client-based focused groups, we primarily focused on groups comprised of community health workers (CHWs) and providers. METHODS: A qualitative study using focus-group discussions, incidence narrative, and informant interviews amongst voluntary participants. Six focus groups were comprised of CHWs, patient couples, midwives, and clinical officers (n = 33) at two rural health centers referring to Kamuzu Central Hospital. Semi-structured questions facilitated discussion of PTB and oral health (inclusive of periodontal disease), including definitions, perception, causation, management, and accepted interventions. RESULTS: Every participant knew of women who had experienced “a baby born too soon”, or preterm birth. All participants recognized both an etiology conceptualization and disease framework for preterm birth, distinguished PTB from miscarriage and macerated stillbirth, and articulated a willingness to engage in studies aimed at prevention or management. Identified gaps included: (1) discordance in the definition of PTB (i.e., 28–34 weeks or less than the 8(th) month, but with a corresponding fetal weight ranging 500 to 2300 grams); (2) utility and regional availability of antenatal steroids for prevention of preterm infant morbidity and mortality; (3) need for antenatal referral for at-risk women, or with symptoms of preterm birth. There was no evident preference for route of progesterone for the prevention of recurrent PTB. CONCLUSIONS: Qualitative research was useful in (1) identifying gaps in knowledge in urban and rural Malawi, and (2) informing the development of educational materials and implementation of programs or trials ultimately aimed at reducing PTB. As a result of this qualitative work, implementation planning was focused on the gaps in knowledge, dissemination of knowledge (to both patients and providers), and practical solutions to barriers in known efficacious therapies