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Plantain (Plantago lanceolata L.) has been identified by the New Zealand dairy sector as an option for reducing nitrogen losses from grazed pastures. However, there is growing concern over its poor persistence. Reports have suggested that plantain does not tolerate waterlogged soils; however, there is little scientific evidence to support those claims. Thus, the present study aimed to investigate the impact of waterlogging on plantain growth and survival. In a glasshouse, three water treatments were applied to plantain plants in pots: control (soil water below field capacity but not limited), wet (soil water marginally above field capacity), and waterlogged (water table 5 cm below the surface) for 39 days, followed by 27 days under the control watering treatment. Leaf elongation and photosynthesis were measured during the experiment. The mean leaf elongation rate of waterlogged plants was 37% lower than control plants during the stress period, but not significantly different than control plants during the recovery period. Waterlogging reduced the rate of photosynthesis in plantain leaves by 15% on average in comparison with control watering during the stress period; however, waterlogged and control plants had a similar mean photosynthesis rate during the recovery period. The results show that plantain growth and photosynthesis were significantly limited under waterlogging; however, the rapid recovery of both processes following the removal of stress suggests that important physiological functions remained intact under waterlogging, possibly due to tolerance mechanisms. These findings suggest that while waterlogging may cause limitations for plantain growth, there is no evidence to suggest that it alone could cause irreversible damage to plants and thus prevent their recovery. Rather, waterlogging stress could undermine the ability of plantain to compete with species that are tolerant of waterlogging within mixed pastures.

The objective of this study was to determine the effect of grazing plantain-based pastures on urine volume, urination frequency, and urinary nitrogen (UN) concentration of dairy cows under a typical pastoral dairy practice offering approximately 25% supplemented feeds. The experiment was a completely randomised design with three pasture treatments (perennial ryegrass–white clover (RGWC); RGWC + low plantain rate (PLL); and RGWC + high plantain rate (PLH)), five replicate plots, and repeated in two sequential grazing periods. Forty-five lactating Friesian × Jersey cows were randomly assigned into three groups of 15 animals each to graze over six days in adaptation paddocks and three days in experimental plots. Urine flow sensors were used to measure urine volume and urinary frequency, while spot urine sampling was conducted to determine nitrogen (N) concentration in cow urine. The results showed that including 25% plantain in the diet (PLH) increased daily urine volume by 44% and the daily number of urinations by 28%, compared to grazing the RGWC pasture. In addition, N concentration in cow urine was decreased by 18 and 29% when the diet contained 18% and 25% plantain, respectively. In conclusion, under a typical dairy farm practice, incorporating plantain into the RGWC pasture with the proportion of 25% plantain in the diet can increase the number of urine patches and reduce the concentration of N in the urine, thereby providing the opportunity to decrease N leaching from pastoral systems.

The use of plantain pasture in dairy systems can potentially reduce nitrogen (N) leaching losses via the lower N concentration in the urine (UNc) of cows. Reducing the urinary N load while cows graze pastures can reduce the risk of N leaching losses from urine patches. Research needs to demonstrate that these environmental benefits are not at the expense of milk production and farm profit. Three groups of 20 cows grazed in the following three pasture treatments: (i) plantain, (ii) plantain–clover mix (plantain, red [Trifolium pratense] and white clover), or (iii) ryegrass-white clover (wc) pastures, from spring to autumn for two years. Each year, pasture intake, diet quality, milk production and animal N (milk and urine) excretion were evaluated in spring, summer, and autumn. The cows grazing the plantain and plantain–clover mix pastures produced similar milk solids as cows grazing ryegrass–wc pasture but reduced their UNc during summer and autumn, when compared to those grazing the plantain–clover mix and ryegrass–wc pastures. Plantain reduced urinary N loads onto pastures by a greater number of urine patches with lower urinary N loading rates. The results demonstrate that plantain pastures do not diminish milk solids production from cows, and the lower UNc from summer to autumn could reduce N being lost to the environment.

In this study, we modelled and compared lactation curves of efficiency of crude protein utilisation (ECPU) and the nitrogen (N) excreta partitioning of milking cows of two contrasting spring-calving pasture-based herds to test some aspects of farming intensification practices on cow performance and N partition. In the low-intensity production system (LIPS), 257 cows were milked once-daily and fed diets comprised of pasture with low supplementary feed inclusion during lactation (304 kg pasture silage/cow). In the high-intensity production system (HIPS), 207 cows were milked twice-daily and fed pasture with higher supplementary feed inclusion (429 kg pasture silage and 1695 kg concentrate/cow). The dietary crude protein (CP) utilisation was calculated for each cow at every herd test date as the ECPU as a proportion of protein yield (PY) from the CP intake (CPI) derived from intake assessments based on metabolisable energy requirements, and the CP balance (CPB) calculated as the difference between CPI and PY. Total N excreta partitioned to faeces (FN) and urine (UN) was estimated by back-calculating UN from FN, considering dietary N, and from N retained in body tissues, taking into account live weight change during the lactation. The higher CPI (2.7 vs. 2.5 kg CP/day), along with the reduced milk yield (1100 kg milk/cow less), of the LIPS cows led to a lower ECPU (23% vs. 31%) and to a higher CPB (2.1 vs. 1.8 kg CP/day) when compared to the HIPS cows. Mean N excreta, and particularly UN, was significantly higher in LIPS cows, and this was explained by higher dietary CP and by the reduced PY when compared to the HIPS cows. Reducing the low-CP supplementation in the “de-intensified” herd lessened the ECPU, resulting in higher UN, which is sensitive in terms of body water eutrophication.

The exact mechanism by which diabetic neuropathy develops is still not fully known, despite our advances in medical knowledge. Progressing neuropathy may occur with a persistently favorable metabolic status in some patients with diabetes mellitus, while, in others, though seldom, a persistently unfavorable metabolic status is not associated with significant neuropathy. This might be significantly due to genetic differences. While recent years have brought compelling progress in the understanding of the pathogenetic background—in particular, accelerated progress is being made in understanding molecular biological mechanisms—some aspects are still not fully understood. A comparatively small amount of information is accessible on this matter; therefore, by summarizing the available data, in this review, we aim to provide a clearer picture of the current state of knowledge, identify gaps in the previous studies, and possibly suggest directions for future studies. This could help in developing more personalized approaches to the prevention and treatment of diabetic neuropathy, while also taking into account individual genetic profiles.

Neuropathy is a serious and frequent complication of type 2 diabetes (T2DM). This study was carried out to search for genetic factors associated with the development of diabetic neuropathy by whole exome sequencing. For this study, 24 patients with long-term type 2 diabetes with neuropathy and 24 without underwent detailed neurological assessment and whole exome sequencing. Cardiovascular autonomic function was evaluated by cardiovascular reflex tests. Heart rate variability was measured by the triangle index. Sensory nerve function was estimated by Neurometer and Medoc devices. Neuropathic symptoms were characterized by the neuropathy total symptom score (NTSS). Whole exome sequencing (WES) was performed on a Thermo Ion GeneStudio S5 system determining the coding sequences of approximately 32,000 genes comprising 50 million base pairs. Variants were detected by Ion Reporter software and annotated using ANNOVAR, integrating database information from dbSNP, ClinVar, gnomAD, and OMIM. Integrative genomics viewer (IGV) was used for visualization of the mapped reads. We have identified genetic variants that were significantly associated with increased (22–49-fold) risk of neuropathy (rs2032930 and rs2032931 of recQ-mediated genome instability protein 2 (RMI2) gene), rs604349 of myosin binding protein H like (MYBPHL) gene and with reduced (0.07–0.08-fold) risk (rs917778 of multivesicular body subunit 12B (MVB12B) and rs2234753 of retinoic acid X receptor alpha (RXRA) genes). The rs2032930 showed a significant correlation with current perception thresholds measured at 5 Hz and 250 Hz for n. medianus (p = 0.042 and p = 0.003, respectively) and at 5 Hz for n. peroneus (p = 0.037), as well as the deep breath test (p = 0.022) and the NTSS (p = 0.023). The rs2032931 was associated with current perception thresholds (p = 0.003 and p = 0.037, respectively), deep breath test (p = 0.022), and NTSS (p = 0.023). The rs604349 correlated with values measured at 2000 (p = 0.049), 250 (p = 0.018), and 5 Hz (p = 0.005) for n. medianus, as well as warm perception threshold measured by Medoc device (p = 0.042). The rs2234753 showed correlations with a current perception threshold measured at 2000 Hz for n. medianus (p = 0.020), deep breath test (p = 0.040), and NTSS (p = 0.003). There was a significant relationship between rs91778 and cold perception threshold (p = 0.013). In our study, genetic variants have been identified that may have an impact on the risk of neuropathy developing in type 2 diabetic patients. These results could open up new opportunities for early preventive measures and might provide targets for new drug developments in the future.

Periodontitis is a microbially driven, host-mediated disease that leads to loss of periodontal attachment and resorption of bone. It is associated with the elevation of systemic inflammatory markers and with the presence of systemic comorbidities. Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the majority of patients have mild symptoms, others experience important complications that can lead to death. After the spread of the COVID-19 pandemic, several investigations demonstrating the possible relationship between periodontitis and COVID-19 have been reported. In addition, both periodontal disease and COVID-19 seem to provoke and/or impair several cardiometabolic complications such as cardiovascular disease, type 2 diabetes, metabolic syndrome, dyslipidemia, insulin resistance, obesity, non-alcoholic fatty liver disease, and neurological and neuropsychiatric complications. Therefore, due to the increasing number of investigations focusing on the periodontitis-COVID-19 relationship and considering the severe complications that such an association might cause, this review aims to summarize all existing emerging evidence regarding the link between the periodontitis-COVID-19 axis and consequent cardiometabolic impairments.

Background and objectives: In the last couple of years, pharmacological management of patients with type 2 diabetes mellitus (T2DM) have been markedly renewed. The aim of this study was to analyse the changes in prescribing patterns of antidiabetic drugs for treating patients with T2DM in Hungary between 2015 and 2020. Material and Methods: In this retrospective, nationwide analysis, we used the central database of the National Health Insurance Fund. We present annual numbers and their proportion of T2DM patients with different treatment regimens. Results: In the period of 2015–2020, the number of incident cases decreased from 60,049 to 29,865, while prevalent cases increased from 682,274 to 752,367. Patients with metformin (MET) monotherapy had the highest prevalence (31% in 2020). Prevalence of insulin (INS) monotherapy continuously but slightly decreased from 29% to 27% while that of sulfonylurea (SU) monotherapy markedly decreased from 37% to 20%. Dipeptidyl peptidase (DPP-4) inhibitors remained popular in 2020 as monotherapy (5%), in dual combination with MET (12%) and in triple combination with MET and SU (5%). The prevalence of patients with sodium-glucose co-transporter-2 (SGLT-2) inhibitors increased from 1% to 4% in monotherapy, from Conclusions: In the period of 2015–2020, we documented important changes in trends of antihyperglycaemic therapeutic patterns in patients with T2DM which followed the new scientific recommendations but remained below our expectations regarding timing and magnitude. More efforts are warranted to implement new agents with cardiovascular/renal benefits into therapeutic management in time, in a much larger proportion of T2DM population, and without delay.

Coronavirus disease 2019 (COVID-19) is a highly heterogeneous disease regarding severity, vulnerability to infection due to comorbidities, and treatment approaches. The hypothalamic–pituitary–adrenal (HPA) axis has been identified as one of the most critical endocrine targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that might significantly impact outcomes after infection. Herein we review the rationale for glucocorticoid use in the setting of COVID-19 and emphasize the need to have a low index of suspicion for glucocorticoid-induced adrenal insufficiency, adjusting for the glucocorticoid formulation used, dose, treatment duration, and underlying health problems. We also address several additional mechanisms that may cause HPA axis dysfunction, including critical illness-related corticosteroid insufficiency, the direct cytopathic impacts of SARS-CoV-2 infection on the adrenals, pituitary, and hypothalamus, immune-mediated inflammations, small vessel vasculitis, microthrombotic events, the resistance of cortisol receptors, and impaired post-receptor signaling, as well as the dissociation of ACTH and cortisol regulation. We also discuss the increased risk of infection and more severe illness in COVID-19 patients with pre-existing disorders of the HPA axis, from insufficiency to excess. These insights into the complex regulation of the HPA axis reveal how well the body performs in its adaptive survival mechanism during a severe infection, such as SARS-CoV-2, and how many parameters might disbalance the outcomes of this adaptation.

Calcium is a ubiquitous signaling molecule that plays a vital role in many physiological processes. Recent work has shown that calcium activity is especially critical in vertebrate neural development. Here, we investigated if calcium activity and neuronal phenotype are correlated only on a population level or on the level of single cells. Using Xenopus primary cell culture in which individual cells can be unambiguously identified and associated with a molecular phenotype, we correlated calcium activity with neuronal phenotype on the single-cell level. This analysis revealed that, at the neural plate stage, a high frequency of low-amplitude spiking activity correlates with an excitatory, glutamatergic phenotype, while high-amplitude spiking activity correlates with an inhibitory, GABAergic phenotype. Surprisingly, we also found that high-frequency, low-amplitude spiking activity correlates with neural progenitor cells and that differentiating cells exhibit higher spike amplitude. Additional methods of analysis suggested that differentiating marker tubb2b-expressing cells exhibit relatively persistent and predictable calcium activity compared to the irregular activity of neural progenitor cells. Our study highlights the value of using a range of thresholds for analyzing calcium activity data and underscores the importance of employing multiple methods to characterize the often irregular, complex patterns of calcium activity during early neural development.

Patients with suspected hip fractures who require further imaging to confirm or disprove the diagnosis may be admitted to orthopaedic or medical departments. We aim to provide evidence regarding the appropriate admission pathway for such patients. This is a retrospective study of all suspected hip fracture patients receiving second-line imaging between 1 January 2015 to 30 June 2016 in one hospital trust. Information was gained from hospital records to determine indication and result of imaging, eventual diagnoses, length of stay, and inpatient mortality. During the study period, 126 patients underwent cross-sectional imaging for clinically suspected but unproven hip fractures. Of these, 27% were positive for hip fractures (n = 34, 3.2% of hip fracture admissions) whilst the remainder were negative. Of the patients without hip fractures, 50 (54%) had a concomitant medical discharge diagnosis. Thirty-one different diagnoses were found in this cohort. This research provides evidence for geriatrician-led admission of patients with suspected but unproven hip fracture, due to the frailty and medical requirements of this patient group.