Real-world pharmacological treatment patterns of patients with young-onset Parkinson’s disease in Japan: a medical claims database analysis

Journal of Neurology - Young-onset Parkinson’s disease is reported to comprise 5–10% of all Parkinson’s disease cases; however, as physicians encounter a limited number of these...     

All-or-none disconnection of pyramidal inputs onto parvalbumin-positive interneurons gates ocular dominance plasticity

Disinhibition is an obligatory initial step in the remodeling of cortical circuits by sensory experience. Our investigation on disinhibitory mechanisms in the classical model of ocular dominance plasticity uncovered an unexpected form of experience-dependent circuit plasticity. In the layer 2/3 of mouse visual cortex, monocular deprivation triggers a complete, “all-or-none,” elimination of connections from pyramidal cells onto nearby parvalbumin-positive interneurons (Pyr→PV). This binary form of circuit plasticity is unique, as it is transient, local, and discrete. It lasts only 1 d, and it does not manifest as widespread changes in synaptic strength; rather, only about half of local connections are lost, and the remaining ones are not affected in strength. Mechanistically, the deprivation-induced loss of Pyr→PV is contingent on a reduction of the protein neuropentraxin2. Functionally, the loss of Pyr→PV is absolutely necessary for ocular dominance plasticity, a canonical model of deprivation-induced model of cortical remodeling. We surmise, therefore, that this all-or-none loss of local Pyr→PV circuitry gates experience-dependent cortical plasticity.

Experience during a postnatal, critical period is essential to properly shape the functional connectivity of cortical circuits. A canonical model of cortical plasticity is the shift in ocular dominance following monocular deprivation (MD), which biases responses toward the nondeprived (ND) eye. Prior research established that MD-induced changes result from the reorganization of excitatory glutamatergic synapses onto excitatory pyramidal neurons (Pyr), which is, in turn, regulated by an inhibitory GABAergic network composed of parvalbumin-positive inhibitory interneurons (PVs). The current consensus is that a reduced, permissive level of inhibition from PV circuits in cortical layer 2/3 is required for plasticity at downstream excitatory synapses and that inhibition above or below the permissive range constrains the response to MD (1–3). Although the notion that rapid cortical disinhibition precedes and initiates the plasticity of glutamatergic connectivity is well established (4, 5), and decades old (6–8), the underlying cellular mechanisms remain unclear.Disinhibition of excitatory cortical neurons could be achieved indirectly, for example by suppressing PV activity via enhancing inhibition from other interneurons through cholinergic neuromodulation (9, 10) but more directly, and likely more effectively, by reducing the excitatory input onto PVs (4, 11–13). Our current investigation uncovered a unique form of experience-dependent plasticity that regulates the connectivity between pyramidal neurons and PVs. We found that the initial response to MD is the functional and structural elimination of ∼50% of these connections. In contrast to the outcome of known mechanisms of synaptic plasticity that manifest in widespread graded changes in synaptic strength, the loss of pyramidal–PV connectivity occurs in a discrete, “all-or-none,” fashion: whereas a subset of connections become completely eliminated, the persistent connections have normal strength. This disconnection is not only rapid but it is transient, affects only very local pyramidal–PV pairs, and, importantly, manipulations that promote/prevent this disconnection also promote/prevent shifts in ocular dominance. We surmise, therefore, that the rapid and transient disconnection of discrete subsets of PV circuits enables the subsequent Hebbian and homeostatic modification of glutamatergic circuitry.     

Exotic myiasis caused by 19 larvae of Cordylobia anthropophaga in Namibia and identified using molecular methods in Japan

A case of exotic myiasis caused by tumbu fly (Cordylobia anthropophaga) parasitism acquired while travelling in the Republic of Namibia is reported. This is the fifth case reported in Japan, and is very unusual in that the patient was infected with 19 larvae. This is also the first case diagnosed using molecular methods in Japan. We cultured the extracted larvae in vitro and successfully obtained pupae.     

Dermatological legal claims in Japan

Health-care safety management has recently been highlighted for patient safety. However, specialist-based risks in clinical settings have hardly been discussed in Japan so far. A review of dermatological legal claims may delineate these risks. This study examined court precedents from the databases "Courts in Japan" and LEX/DB. Thirty-four dermatology-related civil cases were found from 1968-2006. Of the 34 cases, 32 (94%) were judged and two (6%) were retried. Of these 32 cases, 11 (34%) were appealed to higher courts. Among the 34 litigations, the defendants of eight (23%) were dermatology specialists, 20 (59%) were non-dermatologists and six (18%) of unknown specialty. The defendants' negligence was determined at either level in court in 25 of the 34 cases. The negligence in these 25 cases was categorized into five groups: (i) delayed diagnosis (none); (ii) complication during diagnosis procedure (one, 4%); (iii) inappropriate treatment (nine, 36%); (iv) complication during treatment procedure (10, 40%); and (v) insufficient informed consent (five, 20%). The present study may help to improve strategies for health-care safety management in the dermatological field in Japan.     

Fatty acids in component of milk enhance the expression of the cAMP-response-element-binding-protein-binding protein (CBP)/p300 gene in developing rats

Fatty acids in milk are thought to play an important role in intestinal maturation and gene expression in the rat small intestine during the suckling-weaning period. In the present study, we determined the jejunal mRNA level of the cAMP-response-element-binding-protein-binding protein (CBP)/p300, which is one of the chromatin remodelling factors and regulates histone acetylation, during the postnatal period in rats. The mRNA level of CBP/p300 was high during the suckling and middle of the weaning period (day 5 to 20) and then declined sharply to a low level at the end of the weaning period and after weaning. In situ hybridisation also showed that CBP/p300 mRNA levels in the villus as well as the basal membrane clearly decreased after weaning. Rat pups at age 17 d, weaned to a high-fat diet, showed higher levels of CBP/p300 mRNA than those weaned to a low-fat diet. Oral administration of caprylic acid, oleic acid and linoleic acid, which are major fatty acid components in milk, induced jejunal CBP/p300 gene expression. The present results suggest that fatty acids in components of milk enhance expression of the CBP/p300 genes in the small intestine.