Electrophysiological and morphological changes in colonic myenteric neurons from chemotherapy-treated patients: A pilot study

BACKGROUND: Patients receiving anticancer chemotherapy experience a multitude of gastrointestinal side‐effects. However, the causes of these symptoms are uncertain and whether these therapeutics directly affect the enteric nervous system is unknown. Our aim was to determine whether the function and morphology of myenteric neurons are altered in specimens of the colon from chemotherapy‐treated patients. METHODS: Colon specimens were compared from chemotherapy‐treated and non‐treated patients following colorectal resections for removal of carcinoma. Intracellular electrophysiological recordings from myenteric neurons and immunohistochemistry were performed in whole mount preparations. KEY RESULTS: Myenteric S neurons from chemotherapy‐treated patients were hyperexcitable; more action potentials (11.4 ± 9.4, p < 0.05) were fired in response to depolarising current pulses than in non‐treated patients (1.4 ± 0.5). The rheobase and the threshold to evoke action potentials were significantly lower for neurons from chemotherapy‐treated patients compared to neurons from non‐treated patients (p < 0.01). Fast excitatory postsynaptic potential reversal potential was more positive in neurons from chemotherapy‐treated patients (p < 0.05). An increase in the number of neurons with translocation of Hu protein from the cytoplasm to the nucleus was observed in specimens from chemotherapy‐treated patients (103 ± 25 neurons/mm(2), 37.2 ± 7.0%, n = 8) compared to non‐treated (26 ± 5 neurons/mm(2), 11.9 ± 2.7%, n = 12, p < 0.01). An increase in the soma size of neuronal nitric oxide synthase‐immunoreactive neurons was also observed in these specimens. CONCLUSIONS & INFERENCES: This is the first study suggesting functional and structural changes in human myenteric neurons in specimens of colon from patients receiving anticancer chemotherapy. These changes may contribute to the causation of gastrointestinal symptoms experienced by chemotherapy‐treated patients

Mediterranean winter rainfall in phase with African monsoons during the past 1.36 million years

Mediterranean climates are characterized by strong seasonal contrasts between dry summers and wet winters. Changes in winter rainfall are critical for regional socioeconomic development, but are difficult to simulate accurately1 and reconstruct on Quaternary timescales. This is partly because regional hydroclimate records that cover multiple glacial–interglacial cycles2,3 with different orbital geometries, global ice volume and atmospheric greenhouse gas concentrations are scarce. Moreover, the underlying mechanisms of change and their persistence remain unexplored. Here we show that, over the past 1.36 million years, wet winters in the northcentral Mediterranean tend to occur with high contrasts in local, seasonal insolation and a vigorous African summer monsoon. Our proxy time series from Lake Ohrid on the Balkan Peninsula, together with a 784,000-year transient climate model hindcast, suggest that increased sea surface temperatures amplify local cyclone development and refuel North Atlantic low-pressure systems that enter the Mediterranean during phases of low continental ice volume and high concentrations of atmospheric greenhouse gases. A comparison with modern reanalysis data shows that current drivers of the amount of rainfall in the Mediterranean share some similarities to those that drive the reconstructed increases in precipitation. Our data cover multiple insolation maxima and are therefore an important benchmark for testing climate model performance

The process of forest management plans preparation in the Republic of Macedonia: Does it comprise governance principles of participation, transparency and accountability?

Leaving the centralized and trying to embrace the market economy, the forestry sector of the country has been brought to a challenge of moving from government to the new trend of governance. The paper examines whether governance principles of participation, accountability and transparency are comprised in the process of preparation of forest management plans. By scrutinizing the prevailing governance theory through a relevant legislative content analyses and conducted in-depth interviews with relevant stakeholders, the paper provides findings about cooperative forest policy-making in the process of forest management plan preparation through self organizing networks of participants from policy and society. Results obtained from the Law on forests and other related secondary legislation show that only two entities are involved in the preparation process, whereas the Ministry of forestry, agriculture and water economy and the Public enterprise \u201cMacedonian Forest\u201d. On the other hand, results obtained from the conducted in-depth interviews and the legislation content analysis correspond to the situation where the governance principles of participation, transparency and accountability are not respected in the process of creation of forest management plans

A study in university students on the applied methods of transferring information through integrated teaching of anatomy

Ten years ago we introduced an integrated method in the teaching of Anatomy at a university level. It incorporates not only the classical methods of teaching, but also the use of electronic devices. The surveyed students are from five different courses. Despite their various specialization and qualification goals, they all share an insufficient amount of academic lessons on the difficult subject of Anatomy. The aim of this study is to improve the teaching practice, using the method of student feedback. We proposed a short survey to the students, after they completed their Anatomy course. The results were organized into tables and consequently were statistically analyzed. The following report is an analysis of the received data on the importance of the individual teaching methods in the context of integrated teaching. During the study the principle of voluntary participation was explicitly used.

Two Brothers from Macedonia with Gitelman Syndrome

Gitelman syndrome (GS) is a rare renal tubulopathy with an autosomal recessive mode of inheritance, caused by biallelic pathogenic variants in the SLC12A3 gene. The clinical features may overlap with other disorders, such as Bartter syndrome type 3, HNF1B nephropathy or even mitochondrial disease, but can be distinguished by molecular genetic analysis