A Temporal Deep Q Learning for Optimal Load Balancing in Software-Defined Networks.

With the rapid advancement of the Internet of Things (IoT), there is a global surge in network traffic. Software-Defined Networks (SDNs) provide a holistic network perspective, facilitating software-based traffic analysis, and are more suitable to handle dynamic loads than a traditional network. The standard SDN architecture control plane has been designed for a single controller or multiple distributed controllers; however, a logically centralized single controller faces severe bottleneck issues. Most proposed solutions in the literature are based on the static deployment of multiple controllers without the consideration of flow fluctuations and traffic bursts, which ultimately leads to a lack of load balancing among controllers in real time, resulting in increased network latency. Moreover, some methods addressing dynamic controller mapping in multi-controller SDNs consider load fluctuation and latency but face controller placement problems. Earlier, we proposed priority scheduling and congestion control algorithm (eSDN) and dynamic mapping of controllers for dynamic SDN (dSDN) to address this issue. However, the future growth of IoT is unpredictable and potentially exponential; to accommodate this futuristic trend, we need an intelligent solution to handle the complexity of growing heterogeneous devices and minimize network latency. Therefore, this paper continues our previous research and proposes temporal deep Q learning in the dSDN controller. A Temporal Deep Q learning Network (tDQN) serves as a self-learning reinforcement-based model. The agent in the tDQN learns to improve decision-making for switch-controller mapping through a reward-punish scheme, maximizing the goal of reducing network latency during the iterative learning process. Our approach-tDQN-effectively addresses dynamic flow mapping and latency optimization without increasing the number of optimally placed controllers. A multi-objective optimization problem for flow fluctuation is formulated to divert the traffic to the best-suited controller dynamically. Extensive simulation results with varied network scenarios and traffic show that the tDQN outperforms traditional networks, eSDNs, and dSDNs in terms of throughput, delay, jitter, packet delivery ratio, and packet loss.

Long-term complications in patients with childhood-onset nephrotic syndrome.

BACKGROUND: Reports on long-term complications of childhood-onset nephrotic syndrome (NS), such as obesity, osteoporosis, growth failure, and hypertension, are mostly from developed countries not representing South Asian ethnicities. Furthermore, data on cardiovascular health among patients with childhood-onset NS are limited. METHODS: This was an observational study involving patients attending a tertiary care center. Patients aged 15 years and older were examined for long-term complications and remission of NS at their visit in December 2021. Childhood-onset NS meant onset of NS before 10 years of age. Long-term complications included obesity, growth failure, low bone mineral density (BMD) Z score, hypertension, and increased carotid intima-media thickness (cIMT). Long-term remission was defined as no relapse for the last [Formula: see text] 3 consecutive years without immunosuppressive medication to maintain remission. RESULTS: Of 101 patients studied (~ 80% with frequent relapsing (FR)/steroid-dependent (SD) NS), the mean age was 17.6 (± 2.4) years at the time of study. Long-term complications were noted in 89.1% of patients which included one or more of the following: obesity (22.7%), growth failure (31.7%), low BMD Z score (53.5%), hypertension (31.7%), and high cIMT (50.5%). Thirty-nine patients (38.6%) were in long-term remission at the time of the study. Growth failure and low BMD Z scores were less frequent in patients with long-term remission compared to those without long-term remission. CONCLUSIONS: In patients with childhood-onset NS (predominantly FR/SDNS) who were studied at [Formula: see text] 15 years of age, ~ 90% had long-term complications which included high cIMT in 50%. Only ~ 40% were in long-term remission. A higher resolution version of the Graphical abstract is available as Supplementary information.

Lepra Reactions: Mimickers and Mirror to Unmask Complex Cases of Leprosy.

Leprosy is a silent disease with protean manifestations, especially during lepra reactions (LRs). Cases with atypical leprosy or LR simulate a number of conditions misdiagnosed frequently. Here, three classical cases of leprosy are reported for their complex presentation. Leprosy was hidden in Case 1 due to co-existing diabetes. COVID vaccination induced LR unmasked all leprosy lesions, which were extensive, large, bizarre and spreading to various immune zones. Case 2 presented with high-grade fever, tachycardia, generalized erythema and body aches. A detailed workup unveiled his leprosy with a rare presentation of Type 1 lepra reaction (T1LR) with erythroderma and severe systemic symptoms. Case 3 mimicked sarcoidosis and lupus erythematosus (LE) on routine workup. She had facial lesions in the malar area, photosensitivity, joint pains, raised angiotensin-converting enzyme (ACE) levels and positive anti-nuclear antibodies. Peri-appendageal granulomas on histopathology and therapeutic response to multidrug therapy helped in the early diagnosis of leprosy.

Trends in Premature Mortality from Acute Myocardial Infarction in American Indians/Alaska Natives in the United States from 1999 to 2020.

Cardiovascular disease is the leading cause of mortality in American Indian and Alaska Native (AI/AN) groups. They are disproportionately found to have a higher rate of premature myocardial infarction (MI). The Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research were queried to identify premature MI deaths (female <65 years and male <55 years) occurring within the United States between 1999 and 2020. We investigated proportionate mortality trends related to premature MI in AI/ANs stratified by gender. Deaths attributed to acute MI (AMI) were identified using the International Classification of Diseases, Tenth Revision, Clinical Modification codes I21 to I22. We compared the proportional mortality rate because of premature MI with that of a non-AI/AN racial group, which comprised all other races (Blacks, Whites, and Asian/Pacific Islander populations). In AI/ANs, we analyzed a total of 14,055 AMI deaths, of which 3,211 were premature MI deaths corresponding to a proportionate mortality rate of 22.8% (male 20.8%, female 26.2%). The non-AI/AN population had a lower proportionate mortality of 14.8% (male 13.7%, female 16%), p <0.01). On trend analysis, there was no significant improvement over time in the proportionate mortality of AI/ANs (19.8% in 1999 to 21.7% in 2020, p = 0.09). Upon comparison of gender, proportionate mortality of premature MI in women showed a statistically nonsignificant increase from 21.6% in 1999 to 27.3% in 2020 [average annual percent change of 0.7, p = 0.06)]. However, men had a statistically significant decrease in proportionate mortality of premature MI from 18.5% in 1999 to 18.2% in 2020 [average annual percent change of -0.8, p = 0.01)]. AI/ANs have an alarmingly higher rate of proportionate mortality of premature MI than that of other races, with no improvement in the proportionate mortality rates over 20 years, despite an overall downtrend in AMI mortality. Further research to address the reasons for the lack of improvement in premature MI is needed to improve outcomes in this patient population.

Pharmacists and Mental Health First Aid training: A comparative analysis of confidence, mental health assistance behaviours and perceived barriers.

BACKGROUND: Pharmacists are aptly positioned to provide first aid-level assistance to patients experiencing a mental health problem or crisis, yet often lack confidence or perceive barriers to intervention. One potential solution is Mental Health First Aid (MHFA) training-an evidence-based psycho-educational programme. This study evaluates MHFA training within pharmacy by (1) assessing pharmacists' perceptions of the prevalence of patients experiencing a mental health-related problem or crisis, (2) investigating whether MHFA is associated with increased confidence, intervention and assistance quality and (3) examining perceived intervention barriers. METHODS: Pharmacists working in Australia were surveyed. The survey included validated measures and research objectives were assessed using descriptives and ANOVAs. RESULTS: One hundred sixty-one pharmacists were included; 90 MHFA trained and 71 untrained. Overall, 86% of reported encountering at least one patient perceived to be experiencing a mental health problem or crisis in the last year. MHFA trained pharmacists reported being more confident, with notable differences in their confidence to recognize signs, approach and ask someone about suicide. Pharmacists did not intervene ~25% of the time in which a problem/ crisis was identified. When they did intervene, results suggest the assistance was similar in content. Intervention barriers were reported to impede MHFA trained pharmacists significantly less than untrained pharmacists. CONCLUSION: Results suggest pharmacists frequently encounter patients experiencing a mental health problem or crisis and that MHFA training may support pharmacists in helping these patients. Future research can utilize experimental methods to provide causal evidence as to the utility of MHFA training for pharmacists and patients.

Ondansetron-induced QT prolongation among various age groups: a systematic review and meta-analysis.

BACKGROUND: Ondansetron is a selective 5-hydroxytryptamine type 3 serotonin-receptor antagonist with antiemetic properties used inadvertently in the emergency department for controlling nausea. However, ondansetron is linked with a number of adverse effects, including prolongation of the QT interval. Therefore, the purpose of this meta-analysis was to assess the occurrence of QT prolongation in pediatric, adult, and elderly patients receiving oral or intravenously administered ondansetron. METHODS: A thorough electronic search was conducted on PubMed (Medline) and Cochrane Library from the databases' inception to August 10, 2022. Only those studies were considered in which ondansetron was administered orally or intravenously to participants for the treatment of nausea and vomiting. The prevalence of QT prolongation in multiple predefined age groups was the outcome variable. Analyses were conducted using Review manager 5.4 (Cochrane collaboration, 2020). RESULTS: A total of 10 studies involving 687 ondansetron group participants were statistically analyzed. The administration of ondansetron was associated with a statistically significant prevalence of QT prolongation in all age groups. An age-wise subgroup analysis was conducted which revealed that the prevalence of QT prolongation among participants younger than 18 years was not statistically significant, whereas it was statistically significant among participants aged 18-50 years and among patients older than 50 years. CONCLUSIONS: The present meta-analysis provides further evidence that oral or intravenous administration of Ondansetron may lead to QT prolongation, particularly among patients older than 18 years of age.

Impact of educational interventions on utilization patterns of anticancer agents in patients with breast cancer at the specialty oncology care setting in South India.

Aims/Objectives: This study was conducted to assess the utilization patterns of anticancer agents in patients with breast cancer and to provide practice recommendations/educational interventions to optimize medication use in patients with breast cancer. Materials and Methods: This was an ambispective study conducted for a period of 3 years at a private, specialty oncology care hospital in South India. In the initial phase, the selection of anticancer agents, dosage of anticancer agents, and management of chemotherapy-induced nausea and vomiting (CINV) were reviewed retrospectively (using paper medical records) with respect to the National Cancer Comprehensive Network guidelines. The administration of anticancer agents and anti-emetics were reviewed with respect to the hospital drug administration policies. The deviations from the standards were reported, and practice recommendations/educational interventions were developed. Treatment patterns were reevaluated prospectively after providing educational interventions. Descriptive statistics were used to report and compare the results from both phases. Results: During retrospective phase, we observed 80% compliance in the selection of anticancer drugs, 74% compliance in drug dosing, and 63.5% compliance in the administration of anti-cancer agents. After the implementation of educational interventions, we observed 85% compliance in the selection of anticancer agents, 82.3% in their dosing, and 86.9% compliance in the administration of anticancer agents. For the management of CINV, we observed 75% compliance in the selection of drugs (vs. 53% during preintervention), 92% compliance in their dosing (vs. 90% during preintervention), 85.1% compliance in the administration of anti-emetics (vs. 50% during preintervention), and 80% compliance in the management of delayed CINV (vs. 60% during preintervention). Conclusions: Treatment patterns of breast cancer were improved with respect to treatment standards after educational interventions to oncology care team.

Next-Generation Sequencing for Congenital Nephrotic Syndrome: A Multi-Center Cross-Sectional Study from India.

OBJECTIVE: Information on etiology of congenital nephrotic syndrome in non-Caucasian populations is limited. This study aimed to determine the genetic basis of congenital nephrotic syndrome in Indian patients. METHODS: In this observational, cross-sectional study, whole exome sequencing was performed on samples from all children diagnosed with congenital nephrotic syndrome, presenting at centers collaborating in a nationwide registry and biorepository. Analysis was targeted to focus on reported or novel, pathogenic or likely pathogenic variants in 89 genes implicated in etiology of nephrotic syndrome. Sanger sequencing was used to confirm disease-causing variants in patients and allelic segregation of compound heterozygous variants in samples from parents. Inheritance of a shared haplotype was analyzed among ten individuals carrying the most common variant. RESULTS: During 2017-2019, 34 patients with congenital nephrotic syndrome were screened. Consanguinity and similar illness in siblings were reported in eleven patients each. Homozygous or compound heterozygous, pathogenic or likely pathogenic variants were found in NPHS1 in 24 cases, including two novel variants. One patient each had homozygous pathogenic or likely pathogenic known or novel variant in NPHS2, PLCE1, OSGEP and LAMB2 genes. Patients with OSGEP and LAMB2 mutations had phenotype typical of Galloway Mowat and Pierson syndromes, respectively. Three variants in NPHS1 were common to 16 individuals. One reported variant in exon 19 (c.2600G>A; p.Gly867Asp) appears to share a common founder. CONCLUSIONS: A genetic cause was determined for 82.4% patients with congenital nephrotic syndrome. Variants in NPHS1 are most common in Indian patients and founder mutations might be present.

Dental Rehabilitation Following Surgical Management of Temporomandibular Joint Ankylosis: An Interdisciplinary Approach.

Temporomandibular joint ankylosis (TMJ) is a condition affecting mastication, speech, appearance, and oral hygiene to a major extent. The disease is manifested by restriction to complete failure of the TMJ movement due to fibrous or bony union between the condylar head and glenoid fossa. This case report describes a case of a 13-year-old girl with inability to open the mouth along with fractured and discolored anterior teeth due to trauma. Patient was diagnosed as unilateral bony TMJ ankylosis left side and managed by surgical procedure interpositional arthroplasty followed by physiotherapy. Following satisfactory mouth opening, the required dental rehabilitation procedures were done. Combined efforts of pediatric dentists and oral and maxillofacial surgeon with a detailed history, clinical and radiographic assessment helps in correct diagnosis and providing immediate surgical intervention along with the management of associated dental complications in order to reestablish physical and psychological health of the child patient. HOW TO CITE THIS ARTICLE: Patidar D, Fry RR, Sogi S, et al. Dental Rehabilitation Following Surgical Management of Temporomandibular Joint Ankylosis: An Interdisciplinary Approach. Int J Clin Pediatr Dent 2020;13(2):203-205.

Afatinib and lung cancer.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) have an established role in the treatment of non-small-cell lung cancer (NSCLC). First-generation reversible ATP-competitive EGFR-TKIs are approved for the initial treatment of patients with EGFR mutation-positive advanced NSCLC. Afatinib is an irreversible second-generation EGFR-TKI with potent preclinical activity against EGFR (wild type and mutant), HER2, HER4 and EGFR-mutant NSCLC with acquired resistance to reversible EGFR-TKI. LUX-Lung 3 trial demonstrated superiority of afatinib to cisplatin and pemetrexed in the frontline treatment of treatment-naïve patients with advanced adenocarcinoma of the lung and EGFR mutation. Based on these results, afatinib was recently approved for the first-line treatment of NSCLC patients with EGFR mutation. This article summarizes current status of preclinical and clinical development of afatinib in NSCLC.

Inflammatory mediator release by Brugia malayi from macrophages of susceptible host Mastomys coucha and THP-1 and RAW 264.7 cell lines.

OBJECTIVE: To investigate which life stage of the parasite has the ability to stimulate release of pro- or anti-inflammatory mediators from macrophages. METHODS: The human macrophage/monocyte cell line THP-1, the mouse macrophage cell line RAW 264.7 and naive peritoneal macrophages (PM) from the rodent host Mastomys coucha (M. coucha) were incubated at 37 °C in 5% CO(2) atmosphere with extracts of microfilariae (Mf), third stage infective larvae (L(3)) and adult worms (Ad) of Brugia malayi. After 48 hr post exposure, IL-1ß, IL-6, TNF-α, IL-10 and nitric oxide (NO) in cell-free supernatants were estimated. RESULTS: Extracts of all the life stages of the parasite were capable of stimulating pro- (IL-1ß, IL-6 and TNF-α) and anti-inflammatory (IL-10) cytokines in both the cell lines and peritoneal macrophages of M. coucha. Mf was the strongest stimulator of pro-inflammatory cytokines followed by L(3) and Ad; however, Ad was a strong stimulator of IL-10 release. Mf was found to have potential to modulate LPS-induced NO release in RAW cells. Ad-induced NO release was concentration dependent with maximum at 20 µg/mL in both RAW and PMs. CONCLUSIONS: The results show that parasites at all life stages were capable of stimulating pro- (IL-1ß, IL-6 and TNF-α) and anti-inflammatory (IL-10) cytokines and NO release from macrophages of susceptible host M. coucha, human and mouse macrophage cell lines. Mf can suppress the LPS-induced NO release in RAW cells. The findings also show that the two cell lines may provide a convenient in vitro system for assaying parasite-induced inflammatory mediator release.