Comprehensive analysis of the Xya riparia genome uncovers the dominance of DNA transposons, LTR/Gypsy elements, and their evolutionary dynamics.

Transposable elements (TEs) are DNA sequences that can move or replicate within a genome, and their study has become increasingly important in understanding genome evolution and function. The Tridactylidae family, including Xya riparia (pygmy mole cricket), harbors a variety of transposable elements (TEs) that have been insufficiently investigated. Further research is required to fully understand their diversity and evolutionary characteristics. Hence, we conducted a comprehensive repeatome analysis of X. riparia species using the chromosome-level assembled genome. The study aimed to comprehensively analyze the abundance, distribution, and age of transposable elements (TEs) in the genome. The results indicated that the genome was 1.67 Gb, with 731.63 Mb of repetitive sequences, comprising 27% of Class II (443.25 Mb), 16% of Class I (268.45 Mb), and 1% of unknown TEs (19.92 Mb). The study found that DNA transposons dominate the genome, accounting for approximately 60% of the total repeat size, with retrotransposons and unknown elements accounting for 37% and 3% of the genome, respectively. The members of the Gypsy superfamily were the most abundant amongst retrotransposons, accounting for 63% of them. The transposable superfamilies (LTR/Gypsy, DNA/nMITE, DNA/hAT, and DNA/Helitron) collectively constituted almost 70% of the total repeat size of all six chromosomes. The study further unveiled a significant linear correlation (Pearson correlation: r = 0.99, p-value = 0.00003) between the size of the chromosomes and the repetitive sequences. The average age of DNA transposon and retrotransposon insertions ranges from 25 My (million years) to 5 My. The satellitome analysis discovered 13 satellite DNA families that comprise about 0.15% of the entire genome. In addition, the transcriptional analysis of TEs found that DNA transposons were more transcriptionally active than retrotransposons. Overall, the study suggests that the genome of X. riparia is complex, characterized by a substantial portion of repetitive elements. These findings not only enhance our understanding of TE evolution within the Tridactylidae family but also provide a foundation for future investigations into the genomic intricacies of related species.

Comparison between cycloplegic and noncycloplegic refraction in young adult myopes.

SIGNIFICANCE: This study explores the difference between cycloplegic and noncycloplegic refraction in young adult myopes. PURPOSE: From the available literature, it is unclear whether cycloplegia is necessary when refracting young adults. This study investigates the agreement between noncycloplegic autorefraction and cycloplegic autorefraction and investigates factors affecting the agreement between the two methods. METHODS: In total, 125 myopes with ages ranging between 18 and 26 years were included from Australia and Vietnam. Each participant underwent noncycloplegic autorefraction and cycloplegic autorefraction. Cycloplegia was induced with 1% ophthalmic tropicamide. RESULTS: The mean spherical equivalent difference (95% confidence interval) between noncycloplegic autorefraction and cycloplegic autorefraction was -0.20 D (-0.25 to -0.14 D; t124 = -7.18, p<0.0001 ) . A mean difference of >0.25 D was seen in 46.8% of eyes. The lower and upper limits of agreement were -0.80 and 0.41 D, respectively. With univariate analysis, factors including age, degree of refractive error, accommodation amplitude, and distance phorias showed no impact on the average difference between cycloplegic autorefraction and noncycloplegic autorefraction. Yet, eyes with near exophoria ( F2,120 = 6.63, p=0.0019) and Caucasian eyes ( F3,121 = 2.85, p=0.040) exhibited the smallest paired differences. However, in the multivariate analysis, only near exophoria was associated with a lower mean difference. A significantly smaller proportion (34.9%) of eyes with near exophoria had a paired difference of -0.25 D or more compared with esophoria (50%) and orthophoria (65%; χ2 = 6.6, p=0.038). CONCLUSIONS: Noncycloplegic autorefraction results in more myopic refractive error than cycloplegic autorefraction in young adults.

Myopia Progression in Adults: A Retrospective Analysis.

SIGNIFICANCE: Studies on adult myopia progression are limited. This retrospective analysis of a large data set of young adult myopes characterizes myopia progression during adulthood. PURPOSE: This study aimed to determine the mean annual progression of myopia and to estimate the proportion of progressors in adult myopes. METHODS: Longitudinal, noncycloplegic subjective refraction data for young adult myopes (spherical equivalent refractive error, -0.5 D or more), age ranging from 18 to 30 years, were retrospectively analyzed. The mean annual progression, as well as the proportion of progressors (at least -0.50 D shift between visits and annualized progression of -0.25 D or more), was estimated. RESULTS: A total of 354 myopes (230 females [64.7%]), with a mean (standard deviation) age of 22.2 (3.8) years, were considered. The mean (standard deviation) annualized progression was -0.10 (0.21), -0.08 (0.2), and -0.04 (0.21) D in the 18- to 21-year, 22- to 26-year, and 27- to 30-year age groups, respectively ( P = .003). The difference between 18- to 21- and 27- to 30-year age groups was significant ( P = .05), whereas all other pairwise comparisons were not significant. The proportion (95% confidence interval) of progressors in the 18- to 21-, >21- to 26-, and >26- to 30-year age groups was 18.3% (14.9 to 21.7%), 10.9% (7.1 to 14.7%), and 8.8% (4.4 to 13.1%), respectively. The proportion of progressors working or studying in a higher learning/academic environment was 16.2% with an odds ratio (95% confidence interval) for progression of 2.07 (1.15 to 3.74) compared with those in nonacademic environments ( P = .02), with no significant effect of sex or ethnicity. CONCLUSIONS: This study is consistent with other studies on myopia in young adults, which show that myopia does not progress by substantial amounts throughout the adult years, particularly after the age of 21 years. Although future studies may be challenged by the small rates of change and the small proportion of progressors, further research is needed to understand the implications of adult myopia progression on clinical management.

Suprachoroidal silicone oil migration following 27 gauge 3 ports pars plana vitrectomy - a rare complication and its management.

Suprachoroidal silicone oil migration is an unusual complication of small gauge 3 ports Pars plana vitrectomy (3PPV) system. Our objective is to report a retrospective, observational case of an intra-operative suprachoroidal silicone oil (SO) migration during 27 gauge 3PPV and its successful surgical management. A 49 years old male patient with type 2 diabetes, presented to the ophthalmology outpatient department with reduced visual acuity in his right eye. He was diagnosed as having tractional retinal detachment involving macula. During combined phaco-vitrectomy following injection of SO, peripheral choroidal elevations were noted suggesting suprachoroidal SO migration. In an attempt to drain this intra-operatively nasal sclerotomy was enlarged. Post-operative B scan showed significant choroidal detachment for which patient was re-scheduled for surgery after 1 day. Three radial trans-scleral incisions (2 nasal and 1 temporal) for drainage were made at the site of maximum choroidal detachment. By massaging and widening these scleral incisions, suprachoroidal haemorrhage and SO was successfully drained with good post-operative visual improvement.

Teaching the Teacher: Assessing Barriers to Identity Formation of Clinical Teachers in a Developing Country.

PHENOMENON: Clinical teachers' identity formation is understudied in developing countries like Pakistan. Despite producing thousands of international medical graduates per year, Pakistani medical education is still in its infancy. The application of Western medical education methods and theories is beset by unique socio-cultural challenges. These must be identified and addressed to ease our physicians' transition from clinician to teacher and maximize their teaching output in a resource-limited setting. APPROACH: Eight clinical teachers were interviewed from Combined Military Hospital Kharian, Punjab, Pakistan in July 2020. Semi-structured questionnaires were used, and interviews were audio-taped to generate transcripts. These were analyzed qualitatively and coded, developing themes regarding barriers to identity formation. FINDINGS: Six themes reflected possible barriers to identity formation and fell under two domains: individual and systemic issues. At the individual level these themes were: conflicting priorities, lack of autonomy, and language barriers. Systemic issues were found to be: disconnect between educationists and teachers, the absence of incentives, and lack of institutional support. INSIGHT: Identifying barriers to identity formation can aid clinical teachers' development and encourage discourse around providing increased institutional support to teachers to overcome said barriers. Both the individual and the institute are stakeholders in the process of identity formation and dialogue between the two can lead to improved teaching outcomes.

Distinguishing Voluntarily Upregulation of Localized Central Alpha from Widespread Posterior Alpha.

Neurofeedback (NF) training based on alpha upregulation has been widely used on patient and healthy populations. However, active voluntary modulation of central or widespread posterior alpha in response to central alpha feedback is still ambiguous. The objective of this study is to confirm whether patients learn to truly increase alpha power and to determine if patients modulate central or widespread alpha power when alpha feedback is provided from central brain region. This EEG-based NF study was conducted on seven paraplegic patients with same injury type, pain location, and sensitization to ensure homogeneity. In addition to routine NF training sessions, various experiments were performed to compare alpha NF modulation received from C4 with alpha shift during cognitive tasks, occipital or parieto-occipital cortex, and Laplacian montage which is expected to separate localized alpha from widespread alpha, to attain objectives. Moreover, imaginary coherence analysis in alpha band was also performed to check whether C4 training site is coupled with other brain regions and to confirm whether activity at training site leads/lags the activity of other brain regions. The results indicate widespread alpha modulation in patients during regular NF sessions (p < 0.05) with large effect size (> 0.8), sufficiently high statistical power (> 80%), and a narrower confidence interval (CI) in response to NF provided from the central brain region reflecting less uncertainty and higher precision. However, small effect size obtained with Laplacian montage require patients to be trained with Laplacian feedback to achieve a reliable conclusion regarding localized alpha modulation. The outcomes of this study are not only limited to validate true alpha modulation in response to central alpha feedback but also to explore the mechanism of central alpha NF training.

Attitudes and practice of surgeons in reporting medical errors at a tertiary care hospital.

Medical error reporting is essential in creating a culture of accountability in our healthcare system. The aim of this study was to evaluate the frequency of reporting errors by surgeons in our setup and to analyse the factors resulting in under-reporting of medical errors. A total of 96 practicing surgeons at Mayo Hospital, Lahore were surveyed between the months of February, 2018 to June 2018 on their beliefs regarding the reporting of medical errors by means of a specifically designed questionnaire. This study revealed that 71 (74%) respondents had committed a medical error but only 16 (16.6%) of them reported those errors. Major factors in under-reporting of errors included work stress and fear of medico-legal consequences due to disclosure of error. Eighty-four (87.5%) believed that increase in reporting medical errors would contribute to a better system. Most surgeons had a positive view towards the process but believed that the reporting system was ineffective.

P2Y2 Nucleotide Receptor Prompts Human Cardiac Progenitor Cell Activation by Modulating Hippo Signaling.

RATIONALE: Autologous stem cell therapy using human c-Kit+ cardiac progenitor cells (hCPCs) is a promising therapeutic approach for treatment of heart failure (HF). However, hCPCs derived from aged patients with HF with genetic predispositions and comorbidities of chronic diseases exhibit poor proliferative and migratory capabilities, which impair overall reparative potential for injured myocardium. Therefore, empowering functionally compromised hCPCs with proregenerative molecules ex vivo is crucial for improving the therapeutic outcome in patients with HF. OBJECTIVE: To improve hCPC proliferation and migration responses that are critical for regeneration by targeting proregenerative P2Y2 nucleotide receptor (P2Y2R) activated by extracellular ATP and UTP molecules released following injury/stress. METHODS AND RESULTS: c-Kit+ hCPCs were isolated from cardiac tissue of patients with HF undergoing left ventricular assist device implantation surgery. Correlations between P2 nucleotide receptor expression and hCPC growth kinetics revealed downregulation of select P2 receptors, including P2Y2R, in slow-growing hCPCs compared with fast growers. hCPC proliferation and migration significantly improved by overexpressing or stimulating P2Y2R. Mechanistically, P2Y2R-induced proliferation and migration were dependent on activation of YAP (yes-associated protein)-the downstream effector of Hippo signaling pathway. CONCLUSIONS: Proliferation and migration of functionally impaired hCPCs are enhanced by P2Y2R-mediated YAP activation, revealing a novel link between extracellular nucleotides released during injury/stress and Hippo signaling-a central regulator of cardiac regeneration. Functional correlations exist between hCPC phenotypic properties and P2 purinergic receptor expression. Lack of P2Y2R and other crucial purinergic stress detectors could compromise hCPC responsiveness to presence of extracellular stress signals. These findings set the stage for subsequent studies to assess purinergic signaling modulation as a potential strategy to improve therapeutic outcome for use of hCPCs in patients with HF.

Multimodal Imaging of Serpiginous Choroiditis.

PURPOSE: To report a case of atypical serpiginous choroiditis with previously unreported findings on optical coherence tomographic angiography. CASE REPORT: A 35-year-old otherwise healthy man had a 1-week history of vision loss in his right eye. The visual acuity in right eye was counting fingers at 1 meter. Fundoscopy showed a classic peripapillary serpiginous lesion and a solitary macular lesion. Fundus fluorescein angiography revealed early hypofluorescence of active lesions with gradual increase in fluorescence across the phase of angiogram. Optical coherence tomography showed hyperreflectivity in outer retinal layers and loss of ellipsoid zone band. The patient was treated with oral prednisone and visual acuity returned to near normal. The inflammation recurred once the patient discontinued corticosteroid therapy. The flare-up was treated with intravenous methylprednisolone followed by oral steroids. Oral azathioprine was added as a steroid-sparing agent and oral prednisone was tapered slowly and discontinued. The visual acuity returned to normal with settlement of all lesions after initiating azathioprine. Optical coherence tomography showed reintegration of retinal anatomy. No recurrence was seen after discontinuation of corticosteroids. Optical coherence tomographic angiography in resolved serpiginous choroiditis was consistent with loss of choriocapillaris homogeneity. CONCLUSIONS: Serpiginous choroiditis may manifest with multifocal lesions and may be confused with relentless placoid chorioretinitis. However, it ends up in a typical geographic scar. Optical coherence tomography can be used to monitor the changes in retinal structure. Choriocapillaris changes as seen on optical coherence tomographic angiography may be a possible mechanism behind the development of choroidal neovascularization in later stages of the disease.

Atypical Acute Posterior Multifocal Placoid Pigment Epitheliopathy.

PURPOSE: To report a case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) with atypical features. CASE REPORT: A 30-year-old otherwise healthy woman presented with a 7-day history of visual disturbance in her left eye. The best corrected visual acuity in her left eye was 6/36. Funduscopy revealed multiple cream-colored placoid lesions, serous macular elevation, and papillitis. Fundus fluorescein angiography revealed early hypofluorescence and late hyperfluorescence. Systemic and neurologic assessments were normal. The case shared features with both APMPPE and Harada's disease, making it a diagnostic challenge. However, APMPPE may rarely mimic Harada's disease when it manifests with atypical features, like serous retinal detachment and papillitis. The patient was managed with oral prednisolone with slow tapering. Her visual acuity improved gradually to 6/12. Neither involvement of fellow eye nor recurrence in same eye was noted for a period of 1 year. CONCLUSIONS: Acute posterior multifocal placoid pigment epitheliopathy may rarely manifest with atypical features, including papillitis and serous retinal detachment, perplexing the diagnosis and management.

The effectiveness of prophylactic proton pump inhibitors for prevention of non-steroidal anti inflammatory drugs associated gastric and duodenal ulcers in elderly.

UNLABELLED: Aims was undertaken to ensure concomitant usage of proton pump inhibitors (PPIs) with Non-Steroidal Anti-inflammatory Drugs (NSAIDs) in Elderly, in order to avoid upper gastrointestinal (GI) symptoms and ulcers. METHODS: Reviewing of 386 patients' prescription on the EMIS (Egton Medical Information Systems) Web, on April 2014. Checking who have not been prescribed PPIs with NSAIDs, offering them appointment for prescription and discussion about risks and benefits of PPIs. Re-audit of 390 patients' prescription on the EMIS Web, on July 2014. Exclusion criteria in the audit and re-audit were; NSAIDs usage for more than 3 years, contra-indications for PPIs, and patients who declined inclusion in the audit. RESULTS: In the first audit cycle, a total of 386 patients' prescription reviewed, 23 (6%) patients were not prescribed PPIs with NSAIDs and were eligible for PPIs prescription. Those patients were contacted by post, an appointment arranged for them and prescribed the PPIs. 12 weeks later a re-audit was done, showed that all patients (100%) who are prescribed NSAIDs are prescribed prophylactic PPIs. None of the patients who are prescribed NSAIDs and PPIs concomitantly developed upper GI symptoms or ulcers. CONCLUSIONS: The audit increased the awareness of the junior doctors of the importance of concomitant prescription of PPIs with NSAIDs, in accordance with the electronic Medical Compendium (eMC) guidelines, to prevent upper GI symptoms and ulcers. That was reflected in the re-audit having 100% of the patients prescribed NSAIDs and PPIs concomitantly.

Evolutionary Dynamics of Satellite DNA Repeats across the Tettigoniidae Family: Insights from Genomic Analysis.

Satellite DNA repeats are repetitive DNA sequences found in eukaryotic genomes, typically consisting of short DNA motifs repeated in tandem arrays. Despite the vast body of literature on satellite DNA repeats in other taxa, investigations specifically targeting Tettigoniidae remain conspicuously absent. Our study aims to fill a critical gap in our understanding of satellitome evolutionary processes shaping Tettigoniidae genomes. Repeatome analysis revealed that the Meconema thalassinum genome comprises 92%, and Phryganogryllacris superangulata had the lowest value of 34%, with an average of 67% in other Tettigoniidae species. The analysis reveals significant variation in the number of satellite DNA repeats across species of the Tettigoniidae family, with M. thalassinum exhibiting the highest count, 246, reported in insects to date and the lowest count, 10, in Pholidoptera griseoptera. Ruspolia dubia and Ruspolia yunnana, which are congeneric species, showcase distinct counts of 104 and 84 families, respectively. Satellite DNA repeats in R. dubia exhibit the highest abundance, constituting 17.2% of the total genome, while the lowest abundance was reported in P. griseoptera, at 5.65%. The genome size correlates weakly with the satellite DNA family count (rs = 0.42, p = 0.29), but a strong correlation exists between satellite abundance and family number (rs = 0.73, p = 0.03). Moreover, the analysis of satellite DNA gain and loss patterns provides insights into the amplification and homogenization of satellite DNA families within the genome, with species-specific repeats exhibiting a positive trend toward amplification. The chromosomal distribution in M. thalassinum displayed that the highest accumulation was observed on Chr12, Chr01, and Chr04, constituting 17.79%, 17.4%, and 17.22% of the total chromosome size, respectively. The chromosome-specific propagation of satellite DNA families was evident, with MthSat01 solely on chromosome 1 and MthSat170 on chromosome 2, sharing 1.64% and 2.33%. The observed conservation and variations in satellite DNA number and abundances, along with distinct patterns of gain and loss, indicate the influence of potentially diverse evolutionary processes shaping the genomic landscape of these insects, which requires further investigation. Furthermore, the differential accumulation of satellite DNA on specific chromosomes implies that potential chromosome-specific functions or structural features influence the retention and proliferation of satellite sequences.

Mean Ocular Perfusion Pressure Effect During Pars Plana Vitrectomy on the Foveal Avascular Zone: A Pilot Study.

Purpose: To evaluate the effect of mean ocular perfusion pressure on the foveal avascular zone (FAZ) area in eyes with successful retinal detachment (RD) surgery. Methods: This prospective pilot fellow eye-controlled study measured the intraoperative mean ocular perfusion pressure in eyes having surgery for rhegmatogenous RD (RRD). Postoperatively, the FAZ area was measured; the change was calculated as the difference in the FAZ area between the operated eye and the contralateral control eye. Results: The study comprised 8 patients with a mean age (±SD) of 53.38 ± 13.92 years. The mean superficial FAZ area was not different between operated eyes and control eyes, while the deep FAZ area was significantly larger in operated eyes. There was a strong negative correlation between the mean ocular perfusion pressure and the change in the deep FAZ area (Spearman ρ, -0.73; P = .04); the correlation between the mean ocular perfusion pressure and the change in the superficial FAZ area was not significant (Spearman ρ, -0.24; P = .57). A significant linear regression was found between the mean ocular perfusion pressure and the change in the deep FAZ area (R2 = 0.388). The predicted enlargement of the deep FAZ area was 0.03 mm with every 1 mm Hg decrease in the mean ocular perfusion pressure. Conclusions: Lower intraoperative mean ocular perfusion pressure is associated with enlargement of the deep FAZ area in eyes having successful RRD surgery.

Outcomes of Haematopoietic Stem Cell Transplantation in Beta Thalassemia Major with Fully Matched Parents as Donor.

OBJECTIVE: To determine the outcome of beta thalassemia major (BTM) patients undergoing haematopoietic stem cells (HSCT), with fully matched parents as donors vs. matched sibling donors (MSD). STUDY DESIGN: Observational Study. Place and Duration of the Study: Department of Clinical Haematology and Bone Marrow Transplantation Centre, Rawalpindi, Pakistan, from January 2013 to July 2023. METHODOLOGY: Group A consisted of BTM patients who underwent HSCT with fully matched siblings as donors, and Group B consisted of BTM patients who underwent HSCT with fully matched parents as donors. Study data included the age and gender of both recipients and donors, source and dose of stem cells infused, and stage and grades of acute and chronic graft versus host disease (GvHD). All patients received Myeloablative conditioning regimen (MAC). Data were collected to assess patients' demographics, response to HSCT, remission rate, disease free survival (DFS), relapse, and GvHD free survival (GRFS), and overall survival (OS). RESULTS: The mean age of the 54 patients was 5.90 ± 3.29 years. The mean TNC and CD34 doses were 4.99 + 1.13 and 5.42 + 3.70, respectively. Mean time for neutrophil engraftment in both groups was 14.88 + 4.51 days and platelets engraftment was 23.0 + 5.35 days. Most common cause of death was neutropenic sepsis followed by aGVHD. Seven patients had graft rejection. There was no significant association found between graft rejection with donor relation though graft rejection was higher in OS in this study was 70.4%. OS was equal in both groups. Disease free survival was superior in MSD (63%) than parent group (57.7%). CONCLUSION: Allogenic bone marrow transplantation with parents as donors in BTM patients yields outcomes comparable to those with matched sibling donors. This finding is especially relevant in regions like Pakistan, where donor registries and high-resolution HLA typing may be limited. KEY WORDS: Beta thalassemia major, Haematopoietic stem cell transplant, Post-transplant outcome.

Design, synthesis, and biological evaluation of HDAC6 inhibitors targeting L1 loop and serine 531 residue.

Histone deacetylases (HDACs) are a group of enzymes that remove acetyl groups from histones, leading to the silencing of genes. Targeting specific isoforms of HDACs has emerged as a promising approach for cancer therapy, as it can overcome drawbacks associated with pan-HDAC inhibitors. HDAC6 is a unique HDAC isoform that deacetylates non-histone proteins and is primarily located in the cytoplasm. It also has two catalytic domains and a zinc-finger ubiquitin binding domain (Zf-UBD) unlike other HDACs. HDAC6 plays a critical role in various cellular processes, including cell motility, protein degradation, cell proliferation, and transcription. Hence, the deregulation of HDAC6 is associated with various malignancies. In this study, we report the design and synthesis of a series of HDAC6 inhibitors. We evaluated the synthesized compounds by HDAC enzyme assay and identified that compound 8g exhibited an IC50 value of 21 nM and 40-fold selective activity towards HDAC6. We also assessed the effect of compound 8g on various cell lines and determined its ability to increase protein acetylation levels by Western blotting. Furthermore, the increased acetylation of α-tubulin resulted in microtubule polymerization and changes in cell morphology. Our molecular docking study supported these findings by demonstrating that compound 8g binds well to the catalytic pocket via L1 loop of HDAC6 enzyme. Altogether, compound 8g represents a preferential HDAC6 inhibitor that could serve as a lead for the development of more potent and specific inhibitors.

Dataset of usage pattern and energy analysis of an Internet of Things-enabled ceiling fan.

Many electrical appliances have progressed from sheer prototypes to viable products by being automated with the help of sensors and Internet of Things (IoT). In this data driven century, there aren't many data-centric solutions for the effective use of residential and commercial ceiling fans. For the said reason, sensors were installed on a remote-controlled BLDC ceiling fan, and a large amount of user data with environmental indicators such as temperature and humidity, was collected. This data along with the fan speed was logged to a cloud server over Wi-Fi using a Wi-Fi enabled microcontroller. The raw data consists of timestamp, temperature, humidity, and fan speed. The data is logged depending on the change of any parameter rather than a specific interval. The logged data is then visualized on the cloud server to monitor the usage patterns of the appliance and its subsequent energy consumption. The dataset is comprised of the fan data from the bedroom, living room, and lounge obtained by the resident's consent. This data is useful for data scientists, environmentalists, fan manufacturers, architects, social scientists, and several other field enthusiasts. The data can be analyzed based on monthly average temperature and humidity energy consumed, operational time per day or month and monthly/weekly summary of usage. Furthermore, by applying Artificial Intelligence (AI) algorithms on such data, it is feasible to extract patterns that indicate the appliance usage and identify changes in the daily routine. Many machine learning techniques can be applied on the dataset to introduce intelligent control of the appliance for adaptable operation without compromising on the comfort level of the user.

Exploring new histone deacetylase 6 inhibitors and their effects on reversing the α-tubulin deacetylation and cell morphology changes caused by methamphetamine.

Indazole-based HDAC6 inhibitors with novel zinc-binding modifications were synthesized and evaluated to determine their potential to inhibit HDAC6. The analogs were subjected to a histone deacetylase (HDAC) enzyme assay, which led to identification of compounds 3a and 3b. Both compounds demonstrated higher potency and selectivity as HDAC6 inhibitors with IC50 values of 9.1 nM and 9.0 nM, respectively, and highlighted the importance of the hydroxamic acid moiety for binding to Zn2+ inside the catalytic pocket of HDAC enzymes. In the neuroblastoma SH-SY5Y cell line, both compounds efficiently acetylated α-tubulin but not histone H3 at a low concentration of 0.5 µM. Moreover, compounds 3a and 3b effectively reversed the deacetylation of α-tubulin caused by methamphetamine in the SH-SY5Y cell line, suggesting the potential usefulness of HDAC6 selective inhibition in restoring blood brain barrier integrity by reversing methamphetamine-induced deacetylation.

SPC-180002, a SIRT1/3 dual inhibitor, impairs mitochondrial function and redox homeostasis and represents an antitumor activity.

Since sirtuins (SIRTs) are closely associated with reactive oxygen species (ROS) and antioxidant system, the development of their selective inhibitors is drawing attention for understanding of cellular redox homeostasis. Here, we describe the pharmacological properties of SPC-180002, which incorporates a methyl methacrylate group as a key pharmacophore, along with its comprehensive molecular mechanism as a novel dual inhibitor of SIRT1/3. The dual inhibition of SIRT1/3 by SPC-180002 disturbs redox homeostasis via ROS generation, which leads to an increase in both p21 protein stability and mitochondrial dysfunction. Increased p21 interacts with and inhibits CDK, thereby interfering with cell cycle progression. SPC-180002 leads to mitochondrial dysfunction by inhibiting mitophagy, which is accompanied by a reduction in oxygen consumption rate. Consequently, SPC-180002 strongly suppresses the proliferation of cancer cells and exerts anticancer effect in vivo. Taken together, the novel SIRT1/3 dual inhibitor, SPC-180002, impairs mitochondrial function and redox homeostasis, thereby strongly inhibiting cell cycle progression and cancer cell growth.

An unusual presentation of type III late onset multiple-acyl-CoA dehydrogenase deficiency leading to a review of its classification system.

Multiple-acyl-CoA dehydrogenase deficiency (MADD) is a rare autosomal recessive disorder which can be split into three types. Type III MADD is associated with acute or subacute proximal muscle weakness and other variable non-specific features making it a challenging diagnosis for the clinician. This case report describes MADD in a 64 year-old lady, thought to be one of the latest first presentations of the disease. Unusually for this condition, the initial presentation was with dyspnoea. Furthermore, since this case provides further evidence that gene variants can predict age of onset, we advocate for further subclassification of type III MADD into late onset MADD (LO-MADD) when homozygous gene variants are present and very LO-MADD when heterozygous gene variants are found.

Impending disaster: rise of the epsilon variant in Pakistan and the way forward.

The constantly mutating severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) does not appear to be slowing down any time soon. All countries, particularly developing countries, must adapt and strategically plan their way of life around the pandemic, while doing everything possible to keep the mortality rate and spread of the newly emerging variants as low as possible, in order to avoid a further blow to the economy and way of life. Pakistan is one such developing country that is currently battling the dangerous delta strain of SARS-COV-2 with limited resources and has recently seen the emergence of an equally transmissible and highly infectious epsilon strain. This is a concerning situation considering that Pakistan's already overburdened health system and faltering economy cannot withstand another dangerous SARS-COV-2 variant attack. This article highlights some strategies for the country to fortify its defences to prevent the epsilon variant from spreading before it is too late, and emphasises that while identifying potential immune evasion mechanisms in SARS-COV-2 variants is critical in the fight against COVID-19, it is also critical to develop methods of efficient and cost-effective detection to identify an early outbreak and then vigilantly and systematically plan area lockdowns before any hope of conquering this pandemic is lost.