Resting platelets rely on oxidative phosphorylation (OXPHOS) and aerobic glycolysis (conversion of glucose to lactate in the presence of oxygen) to generate adenosine triphosphate, whereas activated platelets exhibit a high level of aerobic glycolysis, suggesting the existence of metabolic flexibility in platelets. Mitochondrial pyruvate dehydrogenase kinases (PDK 1-4) play a pivotal role in metabolic flexibility by inhibiting pyruvate dehydrogenase complex. We determined whether metabolic reprogramming, diverting metabolism from aerobic glycolysis back to OXPHOS, would inhibit platelet function. PDKs activity in human and mouse platelets was inhibited with dichloroacetic acid (DCA), a potent inhibitor of all 4 forms of PDK. Human and mouse platelets pretreated with DCA exhibited decreased platelet aggregation to suboptimal doses of collagen, convulxin, thrombin, and adenosine diphosphate concomitant with decreased glucose uptake. Bioenergetics profile revealed that platelets pretreated with DCA exhibited decreased aerobic glycolysis in response to convulxin only. Furthermore, DCA inhibited ATP secretion, thromboxane A2 generation, and tyrosine phosphorylation of Syk and PLCγ2 in response to collagen or convulxin in human and mouse platelets ( < .05 vs vehicle treated). In the flow chamber assay, human and mouse blood pretreated with DCA formed smaller thrombi when perfused over collagen for 10 minutes at an arterial shear rate of 1500 s ( < .05 vs control). Wild-type mice pretreated with DCA were less susceptible to thrombosis in the FeCl-induced carotid and laser injury-induced mesenteric artery thrombosis models ( < .05 vs vehicle control), without altering hemostasis. Targeting metabolic plasticity with DCA may be explored as a novel strategy to inhibit platelet function.

BACKGROUND: A set of enduring conditions have been reported in the literature involving persistent sexual dysfunction after discontinuation of serotonin reuptake inhibiting antidepressants, 5 alpha-reductase inhibitors and isotretinoin. OBJECTIVE: To develop diagnostic criteria for post-SSRI sexual dysfunction (PSSD), persistent genital arousal disorder (PGAD) following serotonin reuptake inhibitors, post-finasteride syndrome (PFS) and post-retinoid sexual dysfunction (PRSD). METHODS: The original draft was designed using data from two published case series (Hogan et al., 2014 and Healy et al., 2018), which represent the largest public collections of data on these enduring conditions. It was further developed with the involvement of a multidisciplinary panel of experts. RESULTS: A set of criteria were agreed upon for each of the above conditions. Features of PSSD, PFS and PRSD commonly include decreased genital and orgasmic sensation, decreased sexual desire and erectile dysfunction. Ancillary non-sexual symptoms vary depending on the specific condition but can include emotional blunting and cognitive impairment. PGAD presents with an almost mirror image of unwanted sensations of genital arousal or irritability in the absence of sexual desire. A new term, post-SSRI asexuality, is introduced to describe a dampening of sexual interest and pleasure resulting from a pre-natal or pre-teen exposure to a serotonin reuptake inhibitor. CONCLUSIONS: These criteria will help in both clinical and research settings. As with all criteria, they will likely need modification in the light of developments.

Se realiza un estudio de la flora briofítica del Parque Natural Montes de Málaga y su entorno, mediante la recolección en un total de 34 localidades. La diversidad briofítica se ha estimado en 125 especies, de las cuales 109 son musgos y 16 hepáticas, no se han encontrado antocerotas. Aschisma cuynetii, Bryum gemmiferum, B. radiculosum, Crossidium aberrans, Fissidens bryoides, Geheebia siccula, Gymnostomum lanceolatum, Pottiopsis caespitosa, Riccia bicarinata, R. ciliifera, R. papillosa, Trichostomum meridionale y Weissia levieri se citan por vez primera de la provincia de Málaga. Rhynchostegiella tubulosa se menciona como novedad para la brioflora de España. Through the collection of samples and study of 34 localities, the bryophytic flora of the Montes de Málaga Natural Park and surroundings areas is carried out. Bryophytic diversity has been estimated at 125 species, of which 109 are mosses and 16 liverworts, hornworts have not been found. Aschisma cuynetii, Bryum gemmiferum, B. radiculosum, Crossidium aberrans, Fissidens bryoides,Geheebia siccula, Gymnostomum lanceolatum, Pottiopsis caespitosa, Riccia bicarinata, R. ciliifera, R. papillosa, Trichostomum meridionale and Weissia levieri are reported for the first time in Málaga province. Rhynchostegiella tubulosa is mentioned as new record to the bryophytic flora of Spain.

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