Tag: nevin manimala

Andrology. 2022 Sep 3. doi: 10.1111/andr.13287. Online ahead of print.

ABSTRACT

BACKGROUND: The dynein-related genes may have a role in the etiology of male infertility, particularly in cases of impaired sperm motility.

OBJECTIVES: The goal of this review is to compile a list of the most important dynein-related candidate genes that may contribute to male factor infertility.

MATERIALS AND METHODS: Databases were searched using the keywords “dynein”, “male”, “infertility” and by applying strict inclusion criteria. A meta-analysis was also performed by using the eligible case-control studies. The odd ratios (OR), the Z-test score, and the level of significance were determined using a fixed model with a p value of 0.05. Funnel plots were used to check for publication bias.

RESULTS: There were 35 studies that met the inclusion criteria. There were a total of fifteen genes responsible for the production of dynein structural proteins, the production of dynein assembling factors, and potentially associated with male infertility. A total of five case-control studies were eligible for inclusion in the meta-analysis. Variants in the dynein-related genes were linked to an increased the risk of male infertility (OR = 21.52, 95% Confidence Interval (CI) 8.34 – 55.50, Z test = 6.35, p < 0.05). The percentage of heterogeneity, I² , was 47.00%. The lack of variants in the dynein genes was an advantage and this was statistically significant.

DISCUSSION: The results from the present review illustrate that pathogenic variants in genes both for dynein synthesis and for dynein assembly factors could be associated with isolated cases of male infertility without any other symptoms.

CONCLUSIONS: The genes addressed in this study, which are involved in both the production and assembly of dynein, could be used as molecular targets for future research into the etiology of sperm motility problems. This article is protected by copyright. All rights reserved.

PMID:36057791 | DOI:10.1111/andr.13287

Ther Innov Regul Sci. 2022 Sep 3. doi: 10.1007/s43441-022-00445-6. Online ahead of print.

ABSTRACT

Even with recent substantive improvements in health care in pediatric populations, considerable need remains for additional safe and effective interventions for the prevention and treatment of diseases in children. The approval of prescription drugs and biological products for use in pediatric settings, as in adults, requires demonstration of substantial evidence of effectiveness and favorable benefit-to-risk. For diseases primarily affecting children, such evidence predominantly would be obtained in the pediatric setting. However, for conditions affecting both adults and children, pediatric extrapolation uses scientific evidence in adults to enable more efficiently obtaining a reliable evaluation of an intervention’s effects in pediatric populations. Bridging biomarkers potentially have an integral role in pediatric extrapolation. In a setting where an intervention reliably has been established to be safe and effective in adults, and where there is substantive evidence that disease processes in pediatric and adult settings are biologically similar, a ‘bridging biomarker’ should satisfy three additional criteria: effects on the bridging biomarker should capture effects on the principal causal pathway through which the disease process meaningfully influences ‘feels, functions, survives’ measures; secondly, the experimental intervention should not have important unintended effects on ‘feels, functions, survives’ measures not captured by the bridging biomarker; and thirdly, in statistical analyses in adults, the intervention’s net effect on ‘feels, functions, survives’ measures should be consistent with what would be predicted by its level of effect on the bridging biomarker. A validated bridging biomarker has considerable potential utility, since an intervention’s efficacy could be extrapolated from adult to pediatric populations if evidence in children establishes the intervention not only to be safe but also to have substantive effects on that bridging biomarker. Proper use of bridging biomarkers could increase availability of reliably evaluated therapies approved for use in pediatric settings, enabling children and their caregivers to make informed choices about health care.

PMID:36057747 | DOI:10.1007/s43441-022-00445-6

Ther Innov Regul Sci. 2022 Sep 3. doi: 10.1007/s43441-022-00451-8. Online ahead of print.

ABSTRACT

OBJECTIVES: There remains ongoing debate regarding the relative efficacy of public (NIH) and private sector funding in bringing biopharmaceutical innovations to market. This paper investigates the significance of each party’s level of funding for obtaining Food and Drug Administration (FDA) authorization.

METHODS: A cohort of research projects linked to 23,230 National Institute of Health grants awarded in the year 2000 was audited to account for patents, where the project led to a product in clinical development and potentially FDA approval. A total of 8126 associated patents led to the identification of 41 therapies that registered clinical trials; 18 of these therapies received FDA approved.

RESULTS: NIH funding for the 18 FDA-approved therapies totaled $0.670 billion, whereas private sector funding (excluding post-approval funding) totaled $44.3 billion. A logistic regression relating the levels of public and private funding to the probability of FDA approval indicates a positive and significant relationship between private sector funding and the likelihood of FDA approval (p ≤ 0.0004). The relationship between public funding and the likelihood of FDA approval is found to be negative and not statistically significant.

CONCLUSION: Our study results underscore that the development of basic discoveries requires substantial additional investments, partnerships, and the shouldering of financial risk by the private sector if therapies are to materialize as FDA-approved medicine. Our finding of a potentially negative relationship between public funding and the likelihood that a therapy receives FDA approval requires additional study.

PMID:36057746 | DOI:10.1007/s43441-022-00451-8

Environ Monit Assess. 2022 Sep 3;194(10):724. doi: 10.1007/s10661-022-10437-6.

ABSTRACT

Land use and land cover (LULC) change analysis of the construction site and its surroundings of the Akkuyu Nuclear Power Plant project in southern Turkey was undertaken in this case study, which was supported by remotely sensed Landsat 8 image composites. The composite images compiled in 2017 and 2021 were prepared on the Google Earth Engine platform. The Random Forest algorithm was used as the classifier model. A high classification performance was obtained for both images (kappa > 0.88, overall accuracy > 90%). After the classification process, LULC maps for both years were generated, and statistical calculations for the LULC change were computed for both the entire study area (15 × 25 km) and a buffer zone with a radius of 1 km around the power plant. In the whole study area, artificial surfaces significantly increased (78.46%), whereas forests (- 8.31%) and barren lands experienced a considerable decrease (- 6.11%). In the 1 km buffer, artificial surfaces predominantly increased (113.94%), while forests and barren lands decreased dramatically (- 69.13% and – 74.28%, respectively). The agricultural areas in the study area were changed into other LULC classes: 9.1% to artificial surfaces, 27.6% to barren lands, and 21.7% to forest. The rise in the area of artificial surfaces was especially noticeable within the 1 km buffer zone: construction activities converted 36.1% of agricultural fields, 54.1% of forests, and 23.2% of barren lands into artificial surfaces. The filling activities on the seashore resulted in a loss of water bodies of up to 26.5%. The study provides an overview of how the LULC classes have evolved on the construction site and in the region. In the end, the study discusses how the current land use preferences in the region contradict the issues and concerns mentioned in the existing body of literature.

PMID:36057743 | DOI:10.1007/s10661-022-10437-6

Insights Imaging. 2022 Sep 4;13(1):145. doi: 10.1186/s13244-022-01282-9.

ABSTRACT

BACKGROUND: Pancreatic neuroendocrine tumors (pNETs) are heterogeneous tumors from the pancreatic neuroendocrine system, and early diagnosis is important for tumor prognosis and treatment. In this study, we aimed to explore the diagnostic value of spectral CT combined with perfusion scanning in improving the detection rate of pNETs.

METHODS: From December 2018 to December 2020, 58 patients with clinically suspected pNETs were prospectively enrolled in the study for one-stop spectral CT combined with perfusion scanning, 36 patients were confirmed with pNETs by histopathology. An independent cohort of 30 patients with pNETs who underwent routine pancreatic perfusion scanning in our hospital during the same period were retrospectively collected. The image characters of pNETs versus tumor-free pancreatic parenchymal were examined.

RESULTS: The detection rate of spectral CT combined with perfusion was 83.1-96.2%. CT values of the pNETs lesions under each single energy in the arterial phase were statistically higher than those of the adjacent normal pancreatic parenchyma. IC, WC and NIC, in the arterial phase of pNETs lesion were all statistically higher than those of the adjacent normal pancreatic parenchyma. The perfusion parameters of pNETs including BF, BV and MSI were significantly higher than those in normal parenchyma. The average effective radiation dose during the perfusion combined energy spectrum enhanced scanning process was 17.51 ± 2.18 mSv.

CONCLUSION: The one-stop spectral CT combined with perfusion scan improves the detection of pNETs according to morphological features, perfusion parameters and energy spectrum characters with a relatively small radiation dose.

PMID:36057734 | DOI:10.1186/s13244-022-01282-9

J Interv Card Electrophysiol. 2022 Sep 3. doi: 10.1007/s10840-022-01365-z. Online ahead of print.

ABSTRACT

BACKGROUND: Recent data have shown an advantage of rhythm control over rate control for the treatment of atrial fibrillation (AF). Nevertheless, the data regarding efficacy of catheter ablation (CA) compared with antiarrhythmic drugs (AADs) in patients with AF is lacking. Therefore, we sought to evaluate recurrence of arrhythmia, all-cause mortality, cardiovascular deaths, stroke/TIA, and all-cause readmissions of CA compared with AAD in patients with AF.

METHODS: Systematically searched through PubMed, Google Scholar, EMBASE, and Cochrane for randomized control trials that compared CA and AAD in atrial fibrillation patients. Review Manager 5.4 and OpenMetaAnalyst were used to analyze the data. Data was pooled for the outcomes using random-effect models (DerSimonian and Laird) and reported as pooled odds ratio (OR).

RESULTS: A total of 4822 patients were included. The CA group had 2417 patients while the AAD group included 2405 patients. Pooled data demonstrated that the CA arm had a statistically significant decrease in risk for recurrence of arrhythmia as compared to AAD (OR 0.25; [95% CI, 0.18-0.36]; p < 0.001). All-cause readmission was statistically significantly lower in CA as compared to AAD (OR 0.33; [95%CI, 0.17-0.63]; p < 0.001). For other secondary outcomes, there was no statistically significant difference between CA and AAD with regard to all-cause mortality (OR 0.75; [95% CI, 0.55-1.03]), cardiovascular death (OR 0.76; [95% CI, 0.22-2.54]), bleeding (OR 1.09, [95% CI 0.74, 1.61]), or stroke/TIA outcome (OR 0.90, [95% CI, 0.59-1.37]).

CONCLUSIONS: In this study of pooled data from 16 RCTs, CA utilization for atrial fibrillation had improved freedom from arrhythmia as well as reduced all-cause readmission compared with AAD.

PMID:36057733 | DOI:10.1007/s10840-022-01365-z

Head Face Med. 2022 Sep 3;18(1):29. doi: 10.1186/s13005-022-00336-z.

ABSTRACT

PURPOSE: This study aimed to examine the relationship between the sphenoid sinus (SS) and surrounding vital structures such as the internal carotid artery (ICA) and optic nerve canal (ONC) as well as the types of attachment of the sphenoidal septa onto these structures.

METHODS: In total, 230 computed tomography (CT) scans were reviewed to study the type of sphenoid sinus pneumatization (SSP), the protrusion and dehiscence of the ICA and ONC, the relationship between the sphenoidal septa and surrounding vital structures as well as pterygoid recess pneumatization (PRP).

RESULTS: The most common SSP was sellar type (58.7%). The rates of protrusion and dehiscence of the ICA were 26.3 and 0.4%, and for the ONC, they were 13 and 1.5%, respectively. The ICA and ONC were most protruded and dehiscent in more extensive SSP. In 21.6% of patients, the intersphenoidal septa (IS) were attached to the wall of the ICA and in 8.6% they were attached to the wall of the ONC. The attachment of IS to the ICA correlated statistically significantly (p < 0.0001) with protrusion of the ICA. Accessory septa were detected in 30.4% of cases with various sites of attachment.

CONCLUSION: To reduce the risk of injury and complications during endoscopic sinus surgery (ESS), surgeons should consider using CT to identify possible bulging and dehiscence of the ICA/ONC and their relationship to the extent of SSP and also to establish the presence of deviation of the sphenoid septum, and the presence of accessory septa.

PMID:36057720 | DOI:10.1186/s13005-022-00336-z

Lipids Health Dis. 2022 Sep 3;21(1):86. doi: 10.1186/s12944-022-01695-x.

ABSTRACT

BACKGROUND: This study aimed to examine whether the neutrophil to high-density lipoprotein cholesterol ratio (NHR) can predict cardiovascular outcomes in normoglycemic individuals with elevated fasting glucose levels.

METHODS: A total of 130,801 participants with normal blood glucose levels were enrolled in the Kailuan study. Participants were categorized according to NHR quartiles and further divided into normal glucose regulation (NGR) and pre-diabetes (pre-DM) subgroups. The follow-up endpoint was major adverse cardiovascular events (CVE), including stroke and myocardial infarction.

RESULTS: Over a median of 12.53 (8.95-13.08) years of follow-up, subjects with NHR levels in the highest quartile experienced more CVE than those with NHR levels in the lowest quartile. Multivariate Cox analyses showed that continuous changes in NHR (hazard ratio, 1.21; 95% confidence interval [CI], 1.15-1.28) and the highest quartile of NHR (hazard ratio, 1.30; 95% CI, 1.21-1.39) were independent predictors of CVE (all P < 0.001). Furthermore, when participants were categorized by both NHR quartile and glucose metabolism status, the NHR level in the highest quartile plus pre-DM group was associated with a 1.60-fold (95% CI, 1.38-1.86; P < 0.001] higher risk of CVE than that in the lowest quartile plus normoglycemic group. Significantly, the addition of NHR only, presence of pre-DM only, or combination of NHR and pre-DM to the prediction algorithm, including traditional risk factors, improved the C-statistic by 0.19, 0.05, and 0.23 (all P < 0.001).

CONCLUSIONS: Elevated NHR or fasting blood glucose level were independently associated with a higher risk of CVE among normoglycemic individuals. Moreover, pre-DM participants with high NHR levels tended to have worse prognosis, suggesting that NHR could provide greater risk stratification value than traditional risk factors for subjects with pre-DM.

PMID:36057713 | DOI:10.1186/s12944-022-01695-x

BMC Vet Res. 2022 Sep 3;18(1):333. doi: 10.1186/s12917-022-03377-3.

ABSTRACT

BACKGROUND: Swine are considered a major source of foodborne salmonellosis, a public health issue further complicated by the circulation of multidrug-resistant Salmonella strains that threaten the safety of the food chain. The current study aimed to identify patterns that can help to understand the epidemiology of antimicrobial resistance (AMR) in Salmonella in pigs in Spain through the application of several multivariate statistical methods to data from the AMR national surveillance programs from 2001 to 2017.

RESULTS: A total of 1,318 pig Salmonella isolates belonging to 63 different serotypes were isolated and their AMR profiles were determined. Tetracycline resistance across provinces in Spain was the highest among all antimicrobials and ranged from 66.7% to 95.8%, followed by sulfamethoxazole resistance (range: 42.5% – 77.8%), streptomycin resistance (range: 45.7% – 76.7%), ampicillin resistance (range: 24.3% – 66.7%, with a lower percentage of resistance in the South-East of Spain), and chloramphenicol resistance (range: 8.5% – 41.1%). A significant increase in the percentage of resistant isolates to chloramphenicol, sulfamethoxazole, ampicillin and trimethoprim from 2013 to 2017 was observed. Bayesian network analysis showed the existence of dependencies between resistance to antimicrobials of the same but also different families, with chloramphenicol and sulfamethoxazole in the centre of the networks. In the networks, the conditional probability for an isolate susceptible to ciprofloxacin that was also susceptible to nalidixic acid was 0.999 but for an isolate resistant to ciprofloxacin that was also resistant to nalidixic acid was only 0.779. An isolate susceptible to florfenicol would be expected to be susceptible to chloramphenicol, whereas an isolate resistant to chloramphenicol had a conditional probability of being resistant to florfenicol at only 0.221. Hierarchical clustering further demonstrated the linkage between certain resistances (and serotypes). For example, a higher likelihood of multidrug-resistance in isolates belonging to 1,4,[5],12:i:- serotype was found, and in the cluster where all isolates were resistant to tetracycline, chloramphenicol and florfenicol, 86.9% (n = 53) of the isolates were Typhimurium.

CONCLUSION: Our study demonstrated the power of multivariate statistical methods in discovering trends and patterns of AMR and found the existence of serotype-specific AMR patterns for serotypes of public health concern in Salmonella isolates in pigs in Spain.

PMID:36057710 | DOI:10.1186/s12917-022-03377-3

Mol Neurobiol. 2022 Sep 3. doi: 10.1007/s12035-022-03017-9. Online ahead of print.

ABSTRACT

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopamine(DA)rgic neurons in the substantia nigra of the midbrain, and primarily causes motor symptoms. While the pathological cause of PD remains uncertain, oxidative damage, neuroinflammation, and energy metabolic perturbation have been implicated. Pyruvate has been shown neuroprotective in animal models for many neurological disorders, presumably owing to its potent anti-oxidative, anti-inflammatory, and energy metabolic properties. We therefore investigated whether exogenous pyruvate could also protect nigral DA neurons from degeneration and reverse the associated motor deficits in an animal model of PD using the DA neuron-specific toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP (20 mg/kg) was injected four times every 2 h into the peritoneum of mice, which resulted in a massive loss of DA neurons as well as an increase in neuronal death and cytosolic labile zinc overload. There were rises in inflammatory and oxidative responses, a drop in the striatal DA level, and the emergence of PD-related motor deficits. In comparison, when sodium pyruvate was administered intraperitoneally at a daily dose of 250 mg/kg for 7 days starting 2 h after the final MPTP treatment, significant relief in the MPTP-induced neuropathology, neurodegeneration, DA depletion, and motor symptoms was observed. Equiosmolar dose of NaCl had no neuroprotective effect, and lower doses of sodium pyruvate did not have any statistically significant effects. These findings suggest that pyruvate has therapeutic potential for the treatment of PD and related neurodegenerative diseases.

PMID:36057709 | DOI:10.1007/s12035-022-03017-9