Comprehensive Insights into Pathophysiology of Alzheimer's Disease: Herbal Approaches for Mitigating Neurodegeneration.

Alzheimer's disease [AD] is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and functional impairment. Despite extensive research, the exact etiology remains elusive. This review explores the multifaceted pathophysiology of AD, focusing on key hypotheses such as the cholinergic hypothesis, hyperphosphorylated Tau Protein and Amyloid ß hypothesis, oxidative stress hypothesis, and the metal ion hypothesis. Understanding these mechanisms is crucial for developing effective therapeutic strategies. Current treatment options for AD have limitations, prompting the exploration of alternative approaches, including herbal interventions. Cholinesterase inhibitors, targeting the cholinergic hypothesis, have shown modest efficacy in managing symptoms. Blocking Amyloid ß [Aß] and targeting hyperphosphorylated tau protein are under investigation, with limited success in clinical trials. Oxidative stress, implicated in AD pathology, has led to the investigation of antioxidants. Natural products, such as Punica granatum Linn, Radix Scutellariae, and Curcuma longa have demonstrated antioxidant properties, along with anti-inflammatory effects, offering potential neuroprotective benefits. Several herbal extracts, including Ginkgo biloba, Bacopa monnieri, and Withania somnifera, have shown promise in preclinical studies. Compounds like Huperzine A, Melatonin, and Bryostatin exhibit neuroprotective effects through various mechanisms, including cholinergic modulation and anti-inflammatory properties. However, the use of herbal drugs for AD management faces limitations, including standardization issues, variable bioavailability, and potential interactions with conventional medications. Additionally, the efficacy and safety of many herbal products remain to be established through rigorous clinical trials. This review also highlights promising natural products currently in clinical trials, such as Resveratrol and Homotaurine, and their potential impact on AD progression. DHA, an omega-3 fatty acid, has shown cognitive benefits, while Nicotine is being explored for its neuroprotective effects. In conclusion, a comprehensive understanding of the complex pathophysiology of AD and the exploration of herbal interventions offer a holistic approach to managing this devastating disease. Future research should address the limitations associated with herbal drugs and further evaluate the efficacy of promising natural products in clinical settings.

Incidence and Parental Perception of Cardiorespiratory Monitor Use in Preterm Infants.

The objective of this study is to examine the incidence and clinical indicators for use of cardiorespiratory (CR) monitor use. We also examined parents' perceptions on the usefulness of home CR monitoring when their preterm infants were discharged from the hospital. A retrospective patients record review was conducted to assess CR monitor use at discharge in preterm infants from January 1, 2016, to December 31, 2017. Participants received a telephone survey that examined parents' CR monitor experiences and use. Over the study period, forty-four infants were discharged home on CR monitor with the incidence rate of 8.1%. Of those, 28 parents were surveyed between 1 and 2 years post discharge. Most parents reported feeling secure but anxious using the CR monitor. Parents who reported experiencing false alarms frequently also reported having feelings of anxiety while using the CR monitor. Findings from this preliminary study support the importance of understanding the role of parent perceptions of families with infants on CR monitors.

Enhancing object detection in aerial images.

Unmanned Aerial Vehicles have proven to be helpful in domains like defence and agriculture and will play a vital role in implementing smart cities in the upcoming years. Object detection is an essential feature in any such application. This work addresses the challenges of object detection in aerial images like improving the accuracy of small and dense object detection, handling the class-imbalance problem, and using contextual information to boost the performance. We have used a density map-based approach on the drone dataset VisDrone-2019 accompanied with increased receptive field architecture such that it can detect small objects properly. Further, to address the class imbalance problem, we have picked out the images with classes occurring fewer times and augmented them back into the dataset with rotations. Subsequently, we have used RetinaNet with adjusted anchor parameters instead of other conventional detectors to detect aerial imagery objects accurately and efficiently. The performance of the proposed three step pipeline of implementing object detection in aerial images is a significant improvement over the existing methods. Future work may include improvement in the computations of the proposed method, and minimising the effect of perspective distortions and occlusions.

Studying the psychology of coping negative emotions during COVID-19: a quantitative analysis from India.

The outbreak of the COVID-19 virus adversely affected the material and mental well-being of the infected individuals and their families. The poor health system combined with lack of fear of infection has created significant negative health effects for people. The present research consider the notable models of coping with negative emotions, including '3Cs' and 'direct action and palliation approach'. With the observation method's help, a detailed perspective was found on people's coping processes, categorized as psychological, control, coherence, and connectedness coping. The present study considers the notable models of dealing with negative feelings, including '3Cs' and 'direct intervention and palliation strategy'. With the observation method's support, a detailed viewpoint was found on people's coping mechanisms, categorized as neurological, regulation, coherence, and connectedness coping. Using the ANOVA and t-tests, a significant augmentation in people's negative emotions was found since the beginning of the pandemic. Using GMM regression technique, 'avoidance', 'proactive preparedness', 'emotional resilience', 'entertainment', and 'spiritualism' were highly significant techniques in curbing the negative emotions during the COVID-19 pandemic. Meanwhile, the LOGIT regression found cumulative negative emotions and emotions about negative career outlooks to be the most significant to bring negative emotions to normalcy. The study suggests that policymakers design a national-level strategy to strengthen the mental health systems to boost mental well-being.

Hyperinsulinemic hypoglycemia in growth restricted convalescent preterm neonates: clinical characteristics and impediments to early diagnosis.

OBJECTIVES: Describe clinical characteristics, course, and risk factors for hyper-insulinemic hypoglycemia (HIH) in preterm infants and identify impediments to early diagnosis. METHODS: Electronic records of infant-mother dyads were used to describe clinical characteristics, lab parameters, and course of HIH. RESULTS: All eight patients (gestational ages 26w0d-29w3d) had intrauterine growth restriction (IUGR) due to placental insufficiency, (4/8) were small for gestational age. All maintained normal glucose levels with glucose infusion during the first 48 h six of eight patients had cholestasis despite being on parenteral nutrition for short time (average 17 days). Four of eight patients were treated with diazoxide (average 22 days). Four of eight patients who recovered spontaneously (average 49 days after diagnosis) responded to continuous feeds and hydrocortisone for other clinical indications. CONCLUSIONS: In IUGR preterms, HIH is asymptomatic, may be prolonged, requiring diazoxide treatment. Transient cholestasis is seen in majority of patients. Euglycemia should be demonstrated on bolus gavage feeds, off glucocorticoids before discontinuing blood glucose monitoring.

Subject-Specific Cognitive Workload Classification Using EEG-Based Functional Connectivity and Deep Learning.

Cognitive workload is a crucial factor in tasks involving dynamic decision-making and other real-time and high-risk situations. Neuroimaging techniques have long been used for estimating cognitive workload. Given the portability, cost-effectiveness and high time-resolution of EEG as compared to fMRI and other neuroimaging modalities, an efficient method of estimating an individual's workload using EEG is of paramount importance. Multiple cognitive, psychiatric and behavioral phenotypes have already been known to be linked with "functional connectivity", i.e., correlations between different brain regions. In this work, we explored the possibility of using different model-free functional connectivity metrics along with deep learning in order to efficiently classify the cognitive workload of the participants. To this end, 64-channel EEG data of 19 participants were collected while they were doing the traditional n-back task. These data (after pre-processing) were used to extract the functional connectivity features, namely Phase Transfer Entropy (PTE), Mutual Information (MI) and Phase Locking Value (PLV). These three were chosen to do a comprehensive comparison of directed and non-directed model-free functional connectivity metrics (allows faster computations). Using these features, three deep learning classifiers, namely CNN, LSTM and Conv-LSTM were used for classifying the cognitive workload as low (1-back), medium (2-back) or high (3-back). With the high inter-subject variability in EEG and cognitive workload and recent research highlighting that EEG-based functional connectivity metrics are subject-specific, subject-specific classifiers were used. Results show the state-of-the-art multi-class classification accuracy with the combination of MI with CNN at 80.87%, followed by the combination of PLV with CNN (at 75.88%) and MI with LSTM (at 71.87%). The highest subject specific performance was achieved by the combinations of PLV with Conv-LSTM, and PLV with CNN with an accuracy of 97.92%, followed by the combination of MI with CNN (at 95.83%) and MI with Conv-LSTM (at 93.75%). The results highlight the efficacy of the combination of EEG-based model-free functional connectivity metrics and deep learning in order to classify cognitive workload. The work can further be extended to explore the possibility of classifying cognitive workload in real-time, dynamic and complex real-world scenarios.

Fetal Inflammatory Response Syndrome Associated With Maternal SARS-CoV-2 Infection.

Amid the coronavirus disease 2019 pandemic, uncertainty exists about the potential for vertical transmission from mothers infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the fetus in utero. In this case report, we aim to demonstrate the occurrence of a fetal inflammatory response syndrome associated with maternal SARS-CoV-2 infection resulting in neonatal morbidity. In this report we describe an infant of a SARS-CoV-2-positive mother born prematurely with late-onset fever, thrombocytopenia, and elevated levels of inflammatory markers, all of which are consistent with a systemic inflammatory response. The neonate was tested for SARS-CoV-2 by using 2 nasopharyngeal swabs 24 hours apart, and results of both were negative. The result of a full workup for additional infectious pathogens was also negative. Although initially in critical condition in the perinatal period, the infant recovered completely before discharge. We hypothesize that this systemic inflammation occurred in response to maternal viral infection in the absence of vertical transmission of the virus. During the coronavirus disease 2019 pandemic, it will be important to consider the virus as a nidus for a fetal inflammatory response syndrome and resulting morbidity, even in the setting of a negative SARS-CoV-2 testing result in the infant.

Exposure to placental insufficiency alters postnatal growth trajectory in extremely low birth weight infants.

Growth in the immediate postnatal period for extremely low birth weight (ELBW, birth weight < 1000 g) infants is an important topic in neonatal medicine. The goal is to ensure adequate postnatal growth and to minimize complications resulting from suboptimal growth. Past efforts have focused on postnatal nutrition as well as on minimizing comorbidities. It has not been systematically assessed whether antenatal factors play a role in postnatal growth. In this report, we conducted a retrospective study on 91 maternal-neonatal pairs. We prospectively collected maternal and neonatal demographic data, neonatal nutrition in the first 7 days of life and after enteral nutrition is fully established, comorbidity data, as well as weight data from birth to 50 weeks corrected gestational age. We developed a linear mixed-effects model to examine the role of placental insufficiency, as defined by fetal Doppler studies, in postnatal weight z-score trajectory over time in the ELBW population. We relied on Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) for model selection. Interestingly, the selected model included a quadratic term of time and a placental insufficiency-by-time interaction term. In a covariate analysis, AIC and BIC both favored a model that included calories intake in the first 7 days of life and the total duration of antibiotics as fixed-effects, but not their interaction terms with time. Overall, we demonstrated for the first time that placental insufficiency, an antenatal factor, is a major determinant of postnatal weight trajectory in the ELBW population. Prospective studies are warranted to confirm our findings.

Non-dialytic management of acute kidney injury in newborns.

Treating acute kidney injury (AKI) in newborns is often challenging due to the functional immaturity of the neonatal kidney. Because of this physiological limitation, renal replacement therapy (RRT) in this particular patient population is difficult to execute and may lead to unwanted complications. Although fluid overload and electrolyte abnormalities, as seen in neonatal AKI, are indications for RRT initiation, there is limited evidence that RRT initiated in the first year of life improves long-term outcome. The underlying cause of AKI in a newborn patient should determine the treatment strategies to restore appropriate renal function. However, our understanding of this common clinical condition remains limited, as no standardized, evidence-based definition of neonatal AKI currently exists. Non-dialytic management of AKI in these patients may restore appropriate renal function to these patients without exposure to complications often encountered with RRT.

Late-onset blueberry muffin lesions following recombinant erythropoietin administration in a premature infant.

Recombinant erythropoietin is being used in premature population for anemia of prematurity. It is considered very safe in this population, although risks are still being evaluated. We report the first case of dermal erythropoiesis as a side effect of recombinant erythropoietin in an extremely prematurely born infant presenting with late-onset blueberry muffin lesions.

The force required to rupture fetal membranes paradoxically increases with acute in vitro repeated stretching.

OBJECTIVE: The purpose of this study was to determine whether acute repetitive stretching causes fetal membranes (FM) weakening. STUDY DESIGN: Cesarean or vaginally delivered FM were repeatedly stretched and thereafter subjected to rupture testing. Rupture strength (RS), work to rupture (WR), and stiffness were determined. Unstretched FM were compared with stretched FM. RESULTS: In the cesarean group, FM stretched to 50% or 75% of the baseline (unstretched) RS for 10-20 cycles of 10 seconds each paradoxically showed increased RS and stiffness. WR decreased compared with baseline. Detailed analysis revealed that even a single stretch cycle initiated these changes to physical properties. Vaginally delivered FM showed similar changes in physical properties, as did separated amnion. CONCLUSION: Acute stretch forces do not directly cause FM weakening.

Fetal membranes from term vaginal deliveries have a zone of weakness exhibiting characteristics of apoptosis and remodeling.

BACKGROUND: Recently we identified a weak zone in term, pre-labor (repeat Cesarean section) human fetal membranes (FM) overlying the cervix with biochemical characteristics suggestive of apoptosis and collagen remodeling. We suggested that this weak zone is the FM rupture initiation site. Vaginally delivered patients have a weak zone in their FM overlying the cervix; a comparable weak zone lies adjacent to the tear line in FM after spontaneous rupture (SROM). METHODS: FM from vaginally delivered patients with artificial rupture (AROM) and SROM were collected. FM of AROM patients were marked per vagina to identify the FM zone overlying the cervix. Postpartum FM were cut, strength tested, and piece strengths were remapped to their former location on a three-dimensional model. A 10-cm diameter zone centered on the marked area (AROM), or defined weak zone (SROM) was compared with the remaining FM. RESULTS: AROM FM exhibit a para-cervical weak zone. SROM FM exhibit a comparable zone on the tear line. The mean rupture strength within weak zones was 60% of the remaining membranes (P <.001). AROM and SROM FM weak zones both exhibit increased matrix metalloproteinase 9, increased poly (ADP-ribose) polymerase I cleavage, decreased tissue inhibitor of metalloproteinase 3 protein, and histology consistent with remodeling and apoptosis. CONCLUSION: Vaginally delivered AROM FM contain a weak zone overlying the cervix. Vaginally delivered SROM FM contain a weak zone adjacent to the tear line that exhibits biochemical and mechanical characteristics suggestive of collagen remodeling and apoptosis comparable to those of the AR FM weak zone.

Proinflammatory cytokines found in amniotic fluid induce collagen remodeling, apoptosis, and biophysical weakening of cultured human fetal membranes.

The mechanisms by which fetal membranes (FM) rupture during the birth process are unknown. We have recently reported that FM weaken, at least in part, because of a developmental process of extracellular matrix remodeling and apoptosis. We now hypothesize that cytokines that normally increase in amniotic fluid at term induce FM collagen remodeling and apoptosis with concomitant weakening. Full-thickness FM fragments were cultured with (0-100 ng/ml) or without tumor necrosis factor (TNF) or interleukin 1, beta (IL1B). Physical properties were then examined with specially adapted industrial rupture strength testing equipment. Cultured FM were also evaluated for evidence of collagen remodeling and apoptosis. Cytokine-treated FM exhibited a dose-dependent decrease in strength and work to rupture. Compared with controls, the highest TNF dose caused maximal decrease in FM rupture strength (13.2 +/- 1.2 N versus 3.8 +/- 1.5 N; P = 0.0003) and work to rupture (0.035 +/- 0.005 J versus 0.005 +/- 0.002 J; P < 0.0001). The highest IL1B dose also decreased rupture strength (12.9 +/- 3.2 versus 4.6 +/- 1.1 N; P = 0.0027) and work to rupture (0.018 +/- 0.005 J versus 0.005 +/- 0.002 J; P < 0.01). Matrix metalloproteinase 9 (MMP9) protein increased, tissue inhibitor of matrix metalloproteinase 3 (TIMP3) protein decreased, and poly (ADP-ribose) polymerase (PARP1) cleavage increased with increasing TNF or IL1B doses (all P < 0.05), suggesting collagen remodeling and apoptosis. TNF and IL1B cause significant weakening of cultured FM. Both cytokines induce biochemical markers in the FM in a manner characteristic of the weak zone of FM overlying the cervix. TNF and or IL1B may be involved in the development of the weak zone of the FM.