ADHD - What Is the Meaning of Sex-dependent Incidence Differences?

There is a clear experience in clinical practice: boys with a diagnosis of ADHD are clearly in greater numbers than girls. It is noteworthy that even in the "older" review articles, the cause of sex-dependent incidence is not mentioned. If we accept the neurodevelopmental hypothesis of such disorder, then the possible genetic predisposition breaks down into two separate groups. On the genome of an individual with ADHD and on the genome of the parents. However, it cannot be overlooked that the incidence of ADHD (3-7%) corresponds to the incidence and sex differences of the number of newborns born at a certain risk (premature birth, immaturity, hypotrophy, hypoxic-ischemic syndrome, low birth weight, etc.). This association of possible genetic predisposition with "external" risks in the genesis of ADHD raises the question of whether a higher incidence of ADHD, as well as higher morbidity and mortality in males, are a) the norm and the female is privileged, or b) the female is the norm and the male is handicapped. The picture of ADHD includes various cognitive dysfunctions with one possible cause in norepinephrine and dopamine insufficiency. Experimental work shows that in response to stress females release more catecholamines in the CNS than males. Since catecholamines stimulate membrane Na+ K+ ATPase activity, this means both the value of the membrane potential and the threshold for activation is increased. Females are more successful in responding to and adapting to a stressful situation due to their higher production of noradrenaline in the CNS.

It is feasible and safe to stop specialized follow-up of asymptomatic lower risk chronic lymphocytic leukemia.

Approximately half of patients with chronic lymphocytic leukemia (CLL) will never require treatment, still they are recommended life-long specialized follow-up (sFU). To prioritize health care resources, local hospital management implemented ending sFU in asymptomatic patients with CLL international prognostic index (CLL-IPI) and CLL without need of treatment (CLL-WONT) low to intermediate risk, who were covered by universal health care. To evaluate the feasibility and safety of ending sFU, we investigated 3-year clinical outcomes among 112 patients selected by clinical assessment to end sFU as compared with 88 patients continuing sFU. Patients who ended sFU were older but otherwise lower risk compared with patients continuing sFU. Overall survival (OS) was similar in patients ending and continuing sFU (3-year OS 87% and 80%, respectively; P=0.16). Hospital visits per patient-year were lower (median 0.7 vs 4.3, P<0.0001) and time to first infection was longer (P=0.035) in patients ending sFU as compared with those who continued sFU: this included fewer COVID infections (8 [7%] vs 17 [18%]; P=0.029) and shorter in-hospital antimicrobial treatment (median 4 vs 12 days, respectively; P=0.026). Finally, one in six patients got re-referred including 4 patients meeting iwCLL criteria for need of treatment. This also resulted in a lower 3-year first treatment rate for patients ending sFU compared with patients continuing sFU (4% vs 23%, respectively; P<0.0001). In conclusion, it is feasible and safe to end sFU for patients with CLL who have low to intermediate risk CLL-IPI and CLL-WONT scores upon thorough clinical evaluation prior to ending specialized follow-up.

Significance of the plasma membrane for the nerve cell function, development and plasticity.

Lipoid character of plasma membrane namely the presence of polyenic fatty acids enables to interact with membrane proteins and in certain extent also to modulate their function. During the development, molecules of membrane fatty acids become more and more complex, and the ratio of polyenic fatty acids/saturated fatty acids in the brain rises, while the concentration of monoenic fatty acids remained relatively stable. This phenomenon is apparent also in the ratio of unsaturated fatty acids OMEGA-3 in plasma of newborns which correlates with the birth weight. Plasma membrane reflects local specializations of nerve cells. Its composition varies in functionally specialized regions called domains. Specialized domains of nerve cells determine the function of dendrites, soma, axon, axon hillock ect. Premature weaning of laboratory rats results in structural changes and in the increase of excitability of neuronal circuits in hypothalamus, septum and hippocampus which indicate the possibility of membrane composition changes. In synapses, transport proteins of synaptic vesicles, act together with the specific proteins of the presynaptic membrane. Membrane proteins determine the release of neurotransmitter at different conditions of synaptic activity, and they can contribute to the recovery of neurotransmitter content after the repeated hyperactivity. In the model of experimental kindling, repeated seizures bring about decreases and distribution changes of synaptic vesicles.

Hypoxia-induced lipid peroxidation in rat brain and protective effect of carnitine and phosphocreatine.

The exposure to hypobaric hypoxia increased lipid peroxidation as indicated by thiobarbituric acid-reactive substances [TBARS] in rat brain. Plasma lactate/pyruvate ratio was used as a marker of hypoxia. We compared the protective effect of alpha-tocopherol with the effect of L-carnitine or phosphocreatine. Rats pretreated with alpha-tocopherol, L-carnitine, or phosphocreatine had lower TBARS levels after the exposure to hypobaric hypoxia. However, lactate/ pyruvate ratio was improved only in rats pretreated with L-carnitine or phosphocreatine. We conclude from our data that, contrary to alpha-tocopherol, protective effects of L-carnitine and phosphocreatine administrations are due to their regulation of metabolic reactions during hypobaric hypoxia rather than to their scavenger activity.