Genetic Variation and Genotype by Environment Interaction for Agronomic Traits in Maize (Zea mays L.) Hybrids.

In order to develop high-yielding genotypes of adapted maize, multilocation trials of maize were performed including forty-five maize hybrids exploiting genetic variability, trait associations, and diversity. The experiments were laid out in an RCB design and data were recorded on eight yield and yield-contributing traits, viz., days to anthesis (AD), days to silking (SD), anthesis-silking interval (ASI), plant height (PH), ear height (EH), kernels per ear (KPE), thousand-kernel weight (TKW), and grain yield (GY). An analysis of variance (ANOVA) showed significant variation present among the different traits under study. The phenotypic coefficient of variance (PCV) showed a higher value than the genotypic coefficient of variance (GCV), indicating the environmental influence on the expression of the traits. High heritability coupled with high genetic advance was found for these traits, indicative of additive gene action. The trait associations showed that genotypic correlation was higher than phenotypic correlation. Based on genetic diversity, the total genotypes were divided into four clusters, and the maximum number of 16 genotypes was found in cluster IV. Among the eight yield and yield-contributing traits, PH, ASI, EH, and TKW were the important traits for variability creation and were mostly responsible for yield. Genotypes G5, G8, G27, G29, and G42 were in the top ranks based on grain yield over locations, while a few others showed region-centric performances; all these genotypes can be recommended upon validation for commercial release. The present findings show the existence of proper genetic variability and divergence among traits, and the identified traits can be used in a maize improvement program.

A Systematic Review on the Role of Βeta-Blockers in Reducing Cardiac Arrhythmias in Long QT Syndrome Subtypes 1-3.

Long QT syndrome (LQTS) is one of the most common inherited cardiac channelopathies with a prevalence of 1:2000. The condition can be congenital or acquired with 15 recognized genotypes; the most common subtypes are LQTS 1, 2, and 3 making up to 85%-90% of the cases. LQTS is characterized by delayed ventricular cardiomyocyte repolarization manifesting on the surface electrocardiogram (EKG) by a prolonged corrected QT (QTc) interval. The mainstay of treatment for this condition involves in part or combination medical therapy via ß-blockers as first-line (or other anti-arrhythmic), left cardiac sympathectomy, or implantable cardiac defibrillator placement. Given the high rate of adverse cardiac events (ACE) or sudden cardiac death (SCD) in this population of patients with this disease, this review seeks to highlight the genotype-specific treatment consensus in ß-blocker therapy of the most common subtypes. A database search of PubMed, PMC, and Medline was conducted to ascertain the most recent data in the last five years on the management of LQTS types 1-3 and the role of ß-blockers in reducing ACE in these types. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were adhered to in the study selection, and selected studies focused on humans, written in the English Language, and within the last five years of LQTS subtypes 1, 2, and 3. Eleven relevant studies were selected after considering inclusion criteria, exclusion criteria, and quality appraisal within the last five years, focusing on ß-blocker selection directed based on the subtypes of LQTS. Two meta-analyses, one cohort study, and eight reviews provided significant data that non-selective ß-blockers unequivocally are of benefit in these LQTS types. Summary of findings suggested nadolol followed by propranolol yields the best results in LQTS 1, while nadolol would yield the best effect in LQTS 2 and 3.

Use of Epoprostenol in the Treatment of Pulmonary Arterial Hypertension.

Pulmonary Hypertension (PH) is defined as a disorder in which the mean Pulmonary Arterial Pressure (mPAP) is greater than 20 mmHg at rest. Pulmonary Arterial Hypertension (PAH) is considered when mPAP is > 20 mmHg and pulmonary vascular resistance (PVR) is ⩾ 3 WU. PAH is a chronic progressive disease resulting in right heart failure and premature death. It is postulated to be due to an inactivating mutation of a gene named bone morphogenetic protein receptor type 2 (BMPR2), whose predominant function is halting vascular proliferation. It has a lamentable prognosis if not rapidly diagnosed and adequately treated. Treatment of PAH has evolved in the past few decades since many related pathways and potential therapeutic targets have been explored. Parenteral prostanoids are the most effective therapeutic options for PAH. Epoprostenol is a synthetic analog of prostacyclin and a potent vasodilator that was Food and Drug Administration (FDA)-approved in December 1995 for intravenous use to treat PAH. It has also been used to treat different PAH subtypes, including connective tissue-related PAH like lupus and systemic sclerosis, congenital heart disease, and drug-induced PAH. It is effective in reducing mortality rates and improving survival rates. Although the use of Epoprostenol for PAH is challenging, it has been one of the most successful therapies used. In this manuscript, we review the pathophysiology of PAH and the risk stratification tool. We also discuss the mechanism of action of PAH-targeted therapies while focusing on the role of epoprostenol that has been investigated in many clinical trials. Finally, we discuss two ongoing clinical trials which highlight some potential therapeutic options.

Untreated Depression During Pregnancy and Its Effect on Pregnancy Outcomes: A Systematic Review.

Depression is characterized by sad, irritated, or empty moods, as well as somatic and cognitive changes such as loss of concentration, anhedonia, hopelessness, loss of appetite, sleep disturbances, and suicidal ideation, all of which have a negative impact on an individual's ability to function. Depression that occurs during pregnancy is known as antenatal depression. The occurrence of depression during pregnancy and afterward is quite high. Women having a history of depression before pregnancy have a high probability of getting depression during pregnancy again. The purpose of the study is to review the effect of untreated depression during pregnancy on maternal and neonatal outcomes. The primary outcomes of this review were the identification of studies showing the relationship between untreated depression during the pregnancy indicated by depression measures and any associated adverse birth outcomes; specifically, low birth weight, small for gestational age, preterm birth, postpartum depression, and infant neurodevelopmental outcome. We reviewed 20 population-based contemporary cohort studies with a range of populations from 54 to 194,494, all of them representing the population of gestational age located in multiple jurisdictions. It was found that maternal depression during pregnancy has a positive association with preterm birth, small for gestational age, stillbirth, low birth weight, and maternal morbidity including perinatal complications, increased operative delivery, and postpartum depression. To prevent these adverse outcomes, depression should be screened, monitored, and managed appropriately keeping risk-benefit in consideration.

A Systematic Review of Fibromyalgia and Recent Advancements in Treatment: Is Medicinal Cannabis a New Hope?

Fibromyalgia syndrome (FMS) is a pain disorder characterized by chronic widespread pain, fatigue, and sleep disturbance, in the absence of any well-defined underlying organic disease. The exact pathophysiology and the mechanism which links different factors related to the disease is still unknown. Due to unknown precise pathogenesis, the coexistence of other diseases, and overlapping clinical features, FMS diagnosis may be laborious. Various treatment strategies are used, only a few Food and Drug Administration (FDA) approved, still we are facing challenges regarding effective treatment. Recently, medicinal cannabis has proven to be effective in chronic pain conditions such as osteoarthritis, neuropathic pain, and other non-cancer chronic pain. However, further research is needed about how the cannabinoid system works with the pain pathway. Using the fact that medicinal cannabis is effective in the treatment of chronic pain and certain rheumatic diseases, in this review, we aim to analyze the role of the cannabinoid system in fibromyalgia syndrome. We followed Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines in searching PubMed, MEDLINE (through PubMed), PubMed Central, and Google Scholar using keywords "fibromyalgia, chronic pain, cannabis, cannabinoids, pharmacotherapy, alternative therapy" and Medical Subject Heading (MeSH) words. After applying inclusion/exclusion criteria and checking for the quality assessment, 22 articles were retrieved and used for the analysis of the role of cannabis in the treatment of fibromyalgia. The two main compounds of cannabis with analgesic and anti-inflammatory properties are cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), and their ratio determines the effect on various symptoms of FMS. We included studies regarding the use of cannabinoids in the treatment of fibromyalgia, investigating the use of nabilone, dronabinol (a synthetic analog of THC), Bedrocan (22.4 mg THC, <1 mg CBD), Bediol (13.4 mg THC, 17.8 mg CBD), and Bedrolite (18.4 mg CBD, <1 mg THC). In the era of the coronavirus disease 2019 (COVID-19) pandemic and opioid crisis, many adverse outcomes are observed in the patients suffering from FMS due to lack of any definitive treatment and promising outcomes from the known treatment options, which led to the need for effective and safer treatment alternatives. Although the studies reviewed in this article suggest that medical cannabis is a safe and effective treatment for fibromyalgia pain, several limitations regarding dosage, length of treatment, adverse effects, long-term follow-up, and dependence needs further investigation.

Statins' Effect on Cognitive Outcome After Traumatic Brain Injury: A Systematic Review.

Traumatic brain injury (TBI), also known as the "Silent Epidemic," is a growing devastating global health problem estimated to affect millions of individuals yearly worldwide with little public recognition, leading to many individuals living with a TBI-related disability. TBI has been associated with up to five times increase in the risk of dementia among multiple neurologic complications compared with the general population. Several therapies, including statins, have been tried and showed promising benefits for TBI patients. In this systematic review, we evaluated the recent literature that tested the role of statins on neurological and cognitive outcomes such as Alzheimer's Disease and non-Alzheimer's dementia in survivors of TBI with various severities. We conducted a systematic search on PubMed, PubMed Central, MEDLINE, and Google Scholar. MeSH terms and keywords were used to search for full-text randomized clinical trials (RCTs), cross-sectional, case-control, cohort studies, systematic reviews, and animal studies published in English. Inclusion and exclusion criteria were applied, and the articles were subjected to quality appraisal by two reviewers. Our data search retrieved 4948 nonduplicate records. A total of 18 studies were included - nine human studies, and nine animal laboratory trials - after meeting inclusion, eligibility, and quality assessment criteria. Simvastatin was the most tested statin, and the oral route of administration was the most used. Eight human studies showed a significant neuroprotective effect and improvement in the cognitive outcomes, including dementia. Four randomized clinical trials with 296 patients showed that statins play a neuroprotective role and improve cognitive outcomes through different mechanisms, especially their anti-inflammatory effect; they were shown to lower tumor necrosis factor (TNF)-α and C-reactive protein (CRP) levels. Also, they decreased axonal injury and cortical thickness changes. In addition, four cohort studies compared a total of 867.953 patients. One study showed a decrease in mortality in statin-treated patients (p=0.05). Another study showed a reduction in the incidence of Alzheimer's disease and related dementias (RR, 0.77; 95% CI, 0.73-0.81), while one study showed a decreased risk of dementia after concussions by 6.13% (p=0.001). On the other hand, one cohort study showed no significant difference with the use of statins. In eight animal trials, statins showed a significant neuroprotective effect, improved cognitive outcomes, and neurological functions. Different molecular and cellular mechanisms were suggested, including anti-inflammatory effects, promoting angiogenesis, neurogenesis, increasing cerebral blood flow, neurite outgrowth, promoting the proliferation and differentiation of neural stem cells, and reducing axonal injury. On the contrary, one study showed no benefit and actual adverse effect on the cognitive outcome. Most of the studies showed promising neuroprotective effects of statins in TBI patients. Cognitive outcomes, especially dementia, were improved. However, the optimal therapeutic protocol is still unknown. Thus, statins are candidates for more advanced studies to test their efficacy in preventing cognitive decline in patients with TBI.

Efficacy and Safety of Intranasal Esketamine in Treatment-Resistant Depression in Adults: A Systematic Review.

Intranasal form of esketamine, the S-enantiomer of racemic ketamine, was approved by the US FDA in 2019 for treatment-resistant depression (TRD) in adults. Since intranasal esketamine is a newly approved drug with a novel mechanism of action, much still remains unknown in regard to its use in TRD. The objective of this study is to systematically review the latest existing evidence on intranasal esketamine, and provide a better insight into its safety and efficacy in TRD in adults. PubMed, MEDLINE (through PubMed), and Google Scholar were systematically searched from 2016 to 2021, using automation tools. After removal of duplicates and screening on the basis of title/abstract, eligibility criteria were applied and quality appraisal was done independently by two reviewers. A total of 10 studies were selected for the final review which included five clinical trials (three short-term trials, one withdrawal design relapse prevention study, and one long-term study), three post hoc studies, one case/non-case study, and one review article. Out of three short-term clinical trials, only one demonstrated a statistically significant difference between treatment with esketamine plus oral antidepressant (OAD) vs placebo plus OAD. The result of the relapse prevention study showed significantly delayed relapse of depressive symptoms in esketamine plus OAD arm when compared to placebo plus OAD arm. Similarly, the result of the long-term clinical trial showed that the improvement in depressive symptoms was found to be sustained in those using esketamine. The most common adverse effects of esketamine included nausea, dizziness, dissociation, headache, vertigo, somnolence, and dysgeusia (altered sense of taste); most were mild-moderate in severity. One case/non-case study reported rare adverse effects including panic attacks, mania, ataxia, akathisia, self-harm ideation, increased loquacity (talkativeness), and autoscopy. Intranasal esketamine has shown efficacy in reducing depressive symptoms in clinical trials, but the clinical meaningfulness of the treatment effect in the real-world population still needs to be explored. Although the safety profile of esketamine appears to be favorable in most clinical trials, some serious side effects are being reported to the FDA Adverse Event Reporting System, and therefore requires further investigation. More robust clinical trials, especially long-term randomized controlled trials are needed which can help provide a better assessment on the efficacy and safety of intranasal esketamine in the treatment of TRD.

Understanding the Turning Point of Patients with Diabetes.

BACKGROUND: The patient's intention to engage in diabetes care is the hallmark of role acceptance as a health manager and implies one's readiness to change. The study aimed to understand the process of having the intention to engage in diabetes care. METHODS: A qualitative study using narrative inquiry was conducted at a public primary care clinic. Ten participants with type 2 diabetes of more than a 1-year duration were selected through purposive sampling. In-depth interviews were conducted using a semi-structured protocol guide and were audio-taped. The interviews were transcribed and the texts were analyzed using a thematic approach with the Atlas.ti ver. 8.0 software (Scientific Software Development GmbH, Berlin, Germany). RESULTS: Three themes emerged from the analysis. The first theme, "Initial reactions toward diabetes," described the early impression of diabetes encompassing negative emotions, feeling of acceptance, a lack of concern, and low level of perceived efficacy. "Process of discovery" was the second overarching theme marking the journey of participants in finding the exact truth about diabetes and learning the consequences of ignoring their responsibility in diabetes care. The third theme, "Making the right decision," highlighted that fear initiated a decision-making process and together with goal-setting paved the way for participants to reach a turning point, moving toward engagement in their care. CONCLUSION: Our findings indicated that fear could be a motivator for change, but a correct cognitive appraisal of diabetes and perceived efficacy of the treatment as well as one's ability are essentially the pre-requisites for patients to reach the stage of having the intention to engage.

Stepwise visualization of membrane pore formation by suilysin, a bacterial cholesterol-dependent cytolysin.

Membrane attack complex/perforin/cholesterol-dependent cytolysin (MACPF/CDC) proteins constitute a major superfamily of pore-forming proteins that act as bacterial virulence factors and effectors in immune defence. Upon binding to the membrane, they convert from the soluble monomeric form to oligomeric, membrane-inserted pores. Using real-time atomic force microscopy (AFM), electron microscopy (EM), and atomic structure fitting, we have mapped the structure and assembly pathways of a bacterial CDC in unprecedented detail and accuracy, focussing on suilysin from Streptococcus suis. We show that suilysin assembly is a noncooperative process that is terminated before the protein inserts into the membrane. The resulting ring-shaped pores and kinetically trapped arc-shaped assemblies are all seen to perforate the membrane, as also visible by the ejection of its lipids. Membrane insertion requires a concerted conformational change of the monomeric subunits, with a marked expansion in pore diameter due to large changes in subunit structure and packing.

Present status and approaches for the sustainable development of community based fish culture in seasonal floodplains of Bangladesh.

Coordination among the different stakeholders at policy planning, implementation and target beneficiary level, particularly among the agencies responsible for development and management of water resources, agriculture and fisheries, is essential for overall sustainable development. Stocking of larger fingerlings at suitable stocking densities of endemic (rohu, catla, mrigal) and exotic (silver carp, bighead carp, common carp/mirror carp) species should be stocked at varying proportion. Floodplain fish production depends only on the natural fertility of the water bodies. Technological interventions should include the installation of low cost bamboo fencing at water inlet and outlet points and setting of ring culverts for maintaining suitable levels of water for fish culture without hampering the production of rice and other crops in the intervention areas, selective stocking with native and exotic carps, restricted fishing for certain period of time and guarding. It is expected to exert positive influences in enhancing the standing crop and biodiversity of non-stocked species of fishes in the intervention seasonal floodplain. Entry of fish larvae, hatchlings and young fry of wild non-stocked fishes into the seasonal floodplains because of large fence spacing (approximately 1.0 cm), could restrict fishing for certain period, undisturbed habitat and guarding could contribute to higher productivity and enhancement of fish biodiversity in the seasonal floodplains. Proper motivation and effective cooperation of the beneficiaries are extremely important to culture fish in the seasonal floodplains under community based management system. Institutional support and constant vigilance from the Department of Fisheries (DoF) and local administrations are indispensable to ensure the sustainability of fish culture initiatives in the seasonal floodplains. Active participation and involvement of the local community people in all stages of fish culture operation beginning from selection of floodplains, formation of floodplain management committee, planning of fish culture activities, exercise of technical intervention, selective stocking with large fingerlings, guarding, monitoring and supervision, adopting harvesting strategies, marketing and distribution of benefits are extremely essential to ensure sustainability of the program. Mutual trust, sense of respect and good working relationship among the committee members are the basic social elements required for the success of community based fish culture initiatives.

Insights into the biosynthesis of the Vibrio cholerae major autoinducer CAI-1 from the crystal structure of the PLP-dependent enzyme CqsA.

CqsA is an enzyme involved in the biosynthesis of cholerae autoinducer-1 (CAI-1), the major Vibrio cholerae autoinducer engaged in quorum sensing. The amino acid sequence of CqsA suggests that it belongs to the family of alpha-oxoamine synthases that catalyse the condensation of an amino acid to an acyl-CoA substrate. Here we present the apo- and PLP-bound crystal structures of CqsA and confirm that it shares structural homology with the dimeric alpha-oxoamine synthases, including a conserved PLP-binding site. The chemical structure of CAI-1 suggests that decanoyl-CoA may be one substrate of CqsA and that another substrate may be l-threonine or l-2-aminobutyric acid. A crystal structure of CqsA at 1.9-A resolution obtained in the presence of PLP and l-threonine reveals an external aldimine that has lost the l-threonine side chain. Similarly, a 1.9-A-resolution crystal structure of CqsA in the presence of PLP, l-threonine, and decanoyl-CoA shows a trapped external aldimine intermediate, suggesting that the condensation and decarboxylation steps have occurred, again with loss of the l-threonine side chain. It is suggested that this side-chain loss, an observation supported by mass spectrometry, is due to a retro-aldol reaction. Although no structural data have been obtained on CqsA using l-2-aminobutyric acid and decanoyl-CoA as substrates, mass spectrometry confirms the expected product of the enzyme reaction. It is proposed that a region of structure that is disordered in the apo structure is involved in the release of product. While not confirming if CqsA alone is able to synthesize CAI-1, these results suggest possible synthetic routes.