Demographic trends and disparities in mortality related to coexisting heart failure and diabetes mellitus among older adults in the United States between 1999 and 2020: A retrospective population-based cohort study from the CDC WONDER database.

Background: Heart Failure (HF) and Diabetes Mellitus (DM) often coexist, and each condition independently increases the likelihood of developing the other. While there has been concern regarding the increasing burden of disease for both conditions individually over the last decade, a comprehensive examination of mortality trends and demographic and regional disparities needs to be thoroughly explored in the United States (US). Methods: This study analyzed death certificates from the CDC WONDER database, focusing on mortality caused by the co-occurrence of HF and DM in adults aged 75 and older from 1999 to 2020. Age-adjusted mortality rates (AAMRs) and annual percent changes (APCs) were computed and categorized by year, gender, race, census region, state, and metropolitan status. Results: A total of 663,016 deaths were reported in patients with coexisting HF and DM. Overall, AAMR increased from 154.1 to 186.1 per 100,000 population between 1999 and 2020, with a notable significant increase from 2018 to 2020 (APC: 11.30). Older men had consistently higher AAMRs than older women (185 vs. 135.4). Furthermore, we found that AAMRs were highest among non-Hispanic (NH) American Indian or Alaskan natives and lowest in NH Asian or Pacific Islanders (214.4 vs. 104.1). Similarly, AAMRs were highest in the Midwestern region and among those dwelling in non-metropolitan areas. Conclusions: Mortality from HF and DM has risen significantly in recent years, especially among older men, NH American Indian or Alaska Natives, and those in non-metropolitan areas. Urgent policies need to be developed to address these disparities and promote equitable healthcare access.

Relationship between SGLT2 inhibitor use and specific cancer types: a systematic review and meta-analysis.

Aim: The study aimed to explore the incidence of cancer as an adverse event to SGLT2 inhibitors (SGLT2i) use in Type 2 diabetes.Materials & methods: The study followed PRISMA guidelines to pool RCTs conforming the inclusion criteria. Random effects model was used to pool risk ratios.Results & conclusion: After reviewing 19 studies, the analysis suggested a possible increased risk of reproductive, breast, thyroid, hematologic/lymphatic, urinary, skin and skeletal cancers with SGLT2i use. Conversely, lower incidences of respiratory and cardiovascular cancers were noted. However, these associations lacked statistical significance. Caution is advised in using SGLT2i due to potential cancer risks, especially in diabetic patients prone to cancer. More RCTs are essential due to limited research in this area.

SGLT2 inhibitors, widely used to manage Type 2 diabetes, provide benefits for blood sugar control, cardiovascular health and kidney function. However, their impact on cancer risk remains unclear. This review and meta-analysis examined randomized controlled trials to evaluate cancer outcomes in adults using SGLT2 inhibitors. Findings indicated mixed effects on various cancer types, with some inhibitors potentially increasing risk while others showed no significant impact. Further research is essential to clarify the relationship between SGLT2 inhibitors and cancer.

Orally self-disintegrating milk protein puffs enriched with food by-products for the elderly.

Supercritical fluid extrusion (SCFX) processing was used to develop milk protein-based orally self-disintegrating puffs enriched with fruit and dairy by-products, designed specifically to cater to the needs of elderly population having swallowing issues and lactose intolerance. Lactose hydrolyzed skim milk powder (LHSMP) was also added in the formulation to mitigate lactose intolerance while LHSMP was also exploited as a precursor for the polymerization of galactose and lactose to generate galacto-oligosaccharides (GOS) in the puffs. This study for the first time took advantage of the unique features of SCFX processing for in-process GOS formation and enrichment of puffs, achieving GOS contents up to 0.48 g/30 g serving of puffs, thereby making them nutritionally superior and functionally attractive snacks. The estimated nutritional profile revealed that SCFX puffs contained higher levels of protein (16.3 g/30 g), fiber (1.6 g/30 g), phenolics and other valuable nutrients compared to the starch-rich, disintegrating Market Baby puffs.

Did the exposure of coacervate droplets to rain make them the first stable protocells?

Membraneless coacervate microdroplets have long been proposed as model protocells as they can grow, divide, and concentrate RNA by natural partitioning. However, the rapid exchange of RNA between these compartments, along with their rapid fusion, both within minutes, means that individual droplets would be unable to maintain their separate genetic identities. Hence, Darwinian evolution would not be possible, and the population would be vulnerable to collapse due to the rapid spread of parasitic RNAs. In this study, we show that distilled water, mimicking rain/freshwater, leads to the formation of electrostatic crosslinks on the interface of coacervate droplets that not only suppress droplet fusion indefinitely but also allow the spatiotemporal compartmentalization of RNA on a timescale of days depending on the length and structure of RNA. We suggest that these nonfusing membraneless droplets could potentially act as protocells with the capacity to evolve compartmentalized ribozymes in prebiotic environments.

Orbital malignant peripheral nerve sheath tumor: A case report and review.

Malignant peripheral nerve sheath tumor of the orbit is an exceedingly rare entity. These tumors exhibit locally aggressive behavior, recurrences, distant metastasis, and poor response to existing treatment protocols. Orbital nerve sheath tumors are often associated with neurofibromatosis 1, and malignant transformation of neurofibroma into malignant nerve sheath tumor has also been seen. The recommended treatment for localized disease is radical or wide surgical excision to achieve negative margins followed by chemoradiation. For extensive disease, chemotherapy and radiotherapy can be utilized to stabilize the disease. Due to poor response and outcomes with current regimens, the focus has been shifted to approaches utilizing molecular targets and immunological agents. Despite all the advancements, the outcomes still remain discouraging for moderate- to high-grade lesions and thus necessitate studies to design promising treatment modalities.

Kharadar spontaneous quintuplets reached their adolescence life: A case report.

Quintuplet pregnancies are associated with significant perinatal morbidity and mortality. The spontaneous quintuplets are a rare occurrence, and the survival is extremely rare. The first quintuplets known to survive infancy to adulthood were the Dionne Quintuplets, born in 1934. Kharadar quintuplets born in 2006, in Karachi Pakistan, were the first set of quintuplets who were born alive and reached their adolescence. A 30-year old women, presented at Kharadar General Hospital (KGH) during the 28th week of gestation for pregnancy evaluation. She was diagnosed with a quintuplet pregnancy with no gross foetal abnormality on ultrasound abdomen. The patient had premature rupture of membrane at 30th week of gestation, and emergency caesarean section was performed. All five quints were born alive, had normal APGAR scores, were premature, and had low birth weight. After birth, all quints were immediately shifted to the neonatal intensive care unit. After a 10 day hospital stay, all quints were discharged. In 2023, all quints celebrated their 17th Birthday.

Exploring perceptions of pilot licensing and training standards: a survey of Canadian student and licensed pilots.

This study investigates the perspectives of Canadian student and licenced pilots on general aviation pilot training and licencing practices. Employing a mixed-methods approach, this research critiques the reliance on flight hours as the sole competence metric and examines the alignment of existing practices with modern aviation's complexities. Findings reveal a divergence in opinions between novice and experienced pilots on flight hours' importance, with a consensus towards a competency-based evaluation model. The study identifies critical shortcomings in existing training practices, such as the challenge of integrating technology, fostering advanced skills, and efficiently utilising instructional resources. It suggests recommendations for regulatory enhancements, aiming to ensure training practices evolve in line with the changing requirements of aviation safety and technology. The conclusion calls for urgent reform, underlining the imperative for training adaptations that can prepare pilots to proficiently manage the complexities of contemporary airspace, thus safeguarding their proficiency and safety.

A survey conducted among Canadian student and licenced pilots to examine perspectives on general aviation pilot training and licencing practices uncovered critical shortcomings. The findings advocate for a strong preference for competency-based evaluations, urging reforms and regulatory improvements to ensure alignment with the evolving landscape of aviation safety and technological advancements.

Insecticidal Activities of Securidaca longepedunculata Fresen Extracts and Feeding Behavior of Schizaphis graminum Rondani: Electropenetrography Approach.

The aphid, Schizaphis graminum Rondani (Hemiptera: Aphididae), is one of the most destructive pests of wheat. It is responsible for significant economic losses in the agricultural sector, with an estimated 45% of wheat fields affected. Plant-based insecticides have seen a rapid increase in popularity in recent years due to their efficacy, cost-effectiveness, biodegradability, and lower toxicity compared to synthetic pesticides. The study aimed to evaluate the toxic potential of S. longipedunculata extracts against S. graminum and investigate the insect's feeding behavior on wheat. Initially macerated in methanol, the different extracts of S. longipedunculata organs were fractionated using n-hexane, chloroform, ethyl acetate, and butanol. The feeding behavior was analyzed by comparing the waveforms generated by the EPG with the control. After 72 h of treatment, the ethyl acetate fraction extracted from root had the highest toxicity against aphids, with mean 26 mortality of S. graminum at LC50 of 330 ppm; 25 mortality S. graminum at LC50 of 400 ppm for leaves; and mean 24.5 mortality S. graminum at LC50 of 540 ppm in stem bark. EPG analysis indicated that the extract fractions enhanced plant tissue resistance by significantly preventing aphid access to the phloem. The toxic effect of the botanical extracts significantly enhanced the chemical composition of the leaf medium, resulting in a drastic reduction in the number of tissue attacks by S. graminum. In summary, besides their toxicity to S. graminum, extracts of S. longipedunculata reinforce the plant's defense mechanisms, significantly reducing the S. graminum population. They also reinforce wheat's defense mechanisms. S. longipedunculata can, therefore, be used as a promising agent in the biological control of S. graminum.

Disease heterogeneity and molecular classification of inflammatory palmoplantar diseases.

BACKGROUND: Palmoplantar pustulosis (PPP) is an inflammatory disease characterized by relapsing eruptions of neutrophil-filled, sterile pustules on the palms and soles that can be clinically difficult to differentiate from non-pustular palmoplantar psoriasis (palmPP) and dyshidrotic palmoplantar eczema (DPE). OBJECTIVE: We sought to identify overlapping and unique PPP, palmPP, and DPE drivers to provide molecular insight into their pathogenesis. METHODS: We performed bulk RNA sequencing of lesional PPP (n = 33), palmPP (n = 5), and DPE (n = 28) samples, as well as 5 healthy nonacral and 10 healthy acral skin samples. RESULTS: Acral skin showed a unique immune environment, likely contributing to a unique niche for palmoplantar inflammatory diseases. Compared to healthy acral skin, PPP, palmPP, and DPE displayed a broad overlapping transcriptomic signature characterized by shared upregulation of proinflammatory cytokines (TNF, IL-36), chemokines, and T-cell-associated genes, along with unique disease features of each disease state, including enriched neutrophil processes in PPP and to a lesser extent in palmPP, and lipid antigen processing in DPE. Strikingly, unsupervised clustering and trajectory analyses demonstrated divergent inflammatory profiles within the 3 disease states. These identified putative key upstream immunologic switches, including eicosanoids, interferon responses, and neutrophil degranulation, contributing to disease heterogeneity. CONCLUSION: A molecular overlap exists between different inflammatory palmoplantar diseases that supersedes clinical and histologic assessment. This highlights the heterogeneity within each condition, suggesting limitations of current disease classification and the need to move toward a molecular classification of inflammatory acral diseases.

Coenzyme Q10 supplementation affects cellular ionic balance: relevance to aging.

Aging results into disruptive physiological functioning and cellular processes that affect the composition and structure of the plasma membrane. The plasma membrane is the major regulator of ionic homeostasis that regulates the functioning of membrane transporters and exchangers. Coenzyme Q10 is a lipid-soluble antioxidant molecule that declines during aging and age-associated diseases. The present study aims to explore the role of Coenzyme Q10 supplementation to rats during aging on membrane transporters and redox biomarkers. The study was conducted on young and old male Wistar rats supplemented with 20 mg/kg b.w. of Coenzyme Q10 per day. After a period of 28 days, rats were sacrificed and erythrocyte membrane was isolated. The result exhibits significant decline in biomarkers of oxidative stress in old control rats when compared with young control. The effect of Coenzyme Q10 supplementation was more pronounced in old rats. The functioning of membrane transporters and Na+/H+ exchanger showed potential return to normal levels in the Coenzyme Q10 treated rats. Overall, the results demonstrate that Coenzyme Q10 plays an important role in maintaining redox balance in cells which interconnects with membrane integrity. Thus, Coenzyme Q10 supplementation may play an important role in protecting age related alterations in erythrocyte membrane physiology.

Progestogen-driven B7-H4 contributes to onco-fetal immune tolerance.

Immune tolerance mechanisms are shared in cancer and pregnancy. Through cross-analyzing single-cell RNA-sequencing data from multiple human cancer types and the maternal-fetal interface, we found B7-H4 (VTCN1) is an onco-fetal immune tolerance checkpoint. We showed that genetic deficiency of B7-H4 resulted in immune activation and fetal resorption in allogeneic pregnancy models. Analogously, B7-H4 contributed to MPA/DMBA-induced breast cancer progression, accompanied by CD8+ T cell exhaustion. Female hormone screening revealed that progesterone stimulated B7-H4 expression in placental and breast cancer cells. Mechanistically, progesterone receptor (PR) bound to a newly identified -58 kb enhancer, thereby mediating B7-H4 transcription via the PR-P300-BRD4 axis. PR antagonist or BRD4 degrader potentiated immunotherapy in a murine B7-H4+ breast cancer model. Thus, our work unravels a mechanistic and biological connection of a female sex hormone (progesterone) to onco-fetal immune tolerance via B7-H4 and suggests that the PR-P300-BRD4 axis is targetable for treating B7-H4+ cancer.

Patient-Centered Outcomes of a Lymphedema Pump in Patients with Symptomatic Lower Extremity Edema.

BACKGROUND: Phlebolymphedema is a challenging condition to manage, with limited options for effective treatment. For patients, this may be debilitating and lead to infection, loss of independence and affect quality of life. This study aims to evaluate patient-reported outcomes of an advanced pneumatic compression device (APCD) in the treatment of lower extremity phlebolymphedema. METHODS: Patients with diagnosis of lower extremity phlebolymphedema at an acute care facility within the New York City Health and Hospitals Cooperation treated with the Flexitouch (FLX) (Tactile Systems Technology, Inc, Minneapolis, Minnesota) APCD from December 2021 to March 2023 were evaluated. Patient-perceived subjective outcomes were assessed via a short questionnaire, with subsequent analysis using chi-squared test. Primary end points were subjective improvements in 1) swelling, 2) pain, and 3) ease of use of device as surrogates for patient satisfaction. Secondary end point was subjective patient-reported compliance, obtained by investigating 1) if patients were trained to use device, and 2) if patients were using the device. RESULTS: A total of 52 participants were included in this study, consisting of 30.8% male and 69.2% female patients with a mean age of 71.7 years. While selection criteria did not exclude unilateral disease or alternative etiologies, we note that the entire study population had been diagnosed with bilateral lower extremity lymphedema in the setting of chronic venous insufficiency. Other patient characteristics including race, comorbidities and smoking status were documented in Table 1. Table 2 demonstrates the results of chi-squared analysis. This study noted significant patient-perceived improvement in swelling and pain (91.4% with P < 0.00001; 85.7% with P = 0.00002 respectively) and patient-reported ease of use of the FLX device (85.7% with P = 0.00002). Additional secondary findings included a majority of patients reporting being trained on how to use FLX and also maintaining compliance with the device (69.2% with P = 0.005; 67.3% with P = 0.012 respectively). CONCLUSIONS: FLX APCD use has been found to demonstrate desirable patient-reported outcomes as a general trend. The participants in this study noted statistically significant subjective improvement in swelling and pain, ease of use of device and adherence to training and compliance with device. FLX appears to be positively received by patients, and the authors recommend its consideration for management of bilateral lower extremity phlebolymphedema.

Cellulose ether and carbopol 971 based gastroretentive controlled release formulation design, optimization and physiologically based pharmacokinetic modeling of ondansetron hydrochloride minitablets.

This study aims to design and optimize ondansetron (OND) gastro-retentive floating minitablets for better and prolonged control of postoperative nausea and vomiting (PONV) with improved patient compliance. Minitablets were directly compressed and encapsulated in a size 2 capsule shell with an overall dose of 24 mg. Central composite design (CCD) was applied keeping one cellulose ether derivative HPMC K15M and Carbopol 971 as variable and used as swelling and rate retarding agents. The other cellulose derivative i.e. sodium carboxymethyl cellulose, along with mannitol, sodium bicarbonate, and talc, were used in fixed quantities. The floating lag time, total floating time, swelling index, in-vitro drug release, and zero-order (RSQ value), were critical quality parameters. The optimized formulation (Fpred) was evaluated for all critical parameters, along with surface morphology, thermal stability, chemical interaction, and accelerated stability. The in silico PBPK modeling was applied to compare the bioavailability of Fpred with reference OND immediate-release tablets. The numerical optimization model predicted >90 % drug release with zero-order at 12 h. In silico PBPK modeling revealed comparable relative bioavailability of Fpred with the reference formulation. The gastroretentive floating minitablets of OND were successfully designed for prolonged emesis control in patients receiving chemotherapeutic agents.

Time from injury to acute surgery for patients with traumatic cervical spinal cord injury in South-East Norway.

Background: The recommended treatment for cervical spinal cord injury (cSCI) is surgical decompression and stabilization within 24 h after injury. The aims of the study were to estimate our institutional compliance with this recommendation and identify potential factors associated with surgical delay. Methods: Population-based retrospective database study of patients operated for cSCI in 2015-2022 within the South-East Norway Health Region (3.1 million inhabitants). Data extracted were demographics, injury description, management timeline, place of primary triage [local hospital (LH) or neurotrauma center (NTC)]. Main outcome variables were: (1) time from injury to surgery at NTC, (2) time from injury to admission NTC, and (3) time from admission NTC to surgery. Results: We found 243 cSCI patients having acute neck surgery. Their median age was 63 years (IQR 47-74 years), 77% were male, 48% were ≥65 years old. Primary triage at an LH occurred in 150/243 (62%). The median time from injury to acute surgery was 27.8 h (IQR 15.4-61.9 h), and 47% had surgery within 24 h. The median time from injury to NTC admission was 5.6 h (IQR 1.9-19.4 h), and 67% of the patients were admitted to the NTC within 12 h. Significant factors associated with increased time from injury to NTC admission were transfer via LH, severe preinjury comorbidities, less severe cSCI, time of injury other than night, absence of multiple injuries. The median time from NTC admission to surgery was 16.7 h (IQR 9.5-31.0 h), and 70% had surgery within 24 h. Significant factors associated with increased time from NTC admission to surgery were increasing age and non-translational injury morphology. Conclusion: Less than half of the patients with cSCI were operated on within the recommended 24 h time frame after injury. To increase the fraction of early surgery, we suggest the following: (1) patients with clinical suspicion of cSCI should be transported directly to the NTC from the scene of the accident, (2) MRI should be performed only at the NTC, (3) at the NTC, surgery should commence on the same calendar day as arrival or as the first operation the following day.

A closely spaced two-port MIMO antenna with a radiation null for out-of-band suppressions for 5G Sub-6 GHz applications.

This paper presents the design and isolation enhancement of a filtering MIMO antenna with a radiation null for out-of-band suppressions suited for 5G sub-6 GHz communications. The MIMO antenna offers -10 dB impedance bandwidth functionality at the most prominent partial spectrum of the 5G NR n78 band for enabling wireless applications in base stations, ranging from 3.4 GHz to 3.61 GHz. To mitigate the redundancy of an RF filter and to achieve a strong filtering response, a radiation null is produced in the gain with four identical rectangular slots, which results in a significant gain drop of more than 8 dBi at the stopband. The geometrical design also allows 30 percent size reduction of single element. Subsequently, a closely spaced (0.11λ0) two-port MIMO antenna is implemented and with the utilization of the proposed rectangular shaped hollow stub parasitic element, the interelement isolation is significantly improved by more than 8 dB over the operational frequency range while retaining the filtering without any additional RF structure. The design simplification, peak gain of 5.4 dBi, near ideal response of diversity gain, ECC less than 0.03, congruency between simulated and measured results, and stable parameters make it a valuable choice for 3.5 GHz sub-6 GHz communications.

Removal and detection of phenols through an SPE-HPLC method using microporous organic networks as adsorbent.

The design and development of a facile synthesis approach to construct novel materials for the rapid adsorption and removal of environmental pollutants are of significant interest. In this work, we report the rational design and facile synthesis of magnetic core-shell-based microporous organic networks, Fe3O4@MON-TBPT-TEB (TTMON, achieved by reacting 2,4,6-tris(p-bromophenyl) triazine and 1,3,5-triethynylbenzene) and Fe3O4@MON-TBPM-DEBP (TDMON, achieved by reacting tetrakis (4-bromophenyl) methane and 4-4'-diethynylbiphenyl). These MONs possessed excellent dispersity, electrostatic attraction as well as plenty of π-π and hydrophobic interaction sites enabled them to efficiently absorb targeted environmental pollutants. TTMON and TDMON exhibited excellent adsorption capacities of 440 and 510 mg g-1, respectively, at 25 °C for 2,4,6-trichlorophenol (TCP). TCP, 2,4-dichlorophenol (DCP), 2-naphthol (2-NT) and 4-nitrophenol (4-NP) from aqueous solution were treated by both MONs, followed by their analysis with high-performance liquid chromatography (HPLC). For TDMON, the proposed SPE-HPLC-UV method showed an LOD of 0.03 µg L-1, LOQ of 0.11 µg L-1, and a wide linear range of 1-1000 µg L-1 for TCP. The adsorption kinetics, thermodynamics, isotherms, effect of pH and humic acid (HA), ionic strength, regeneration, and reusability of the MONs were also studied. The results revealed that the novel-designed MONs have potential applications as efficient adsorbents in sample pretreatment.

Prevalence, Severity Patterns and Risk Factors of Bronchopulmonary Dysplasia in Preterm Infants Younger than 32 Weeks of Gestation in a Tertiary Centre in Oman.

Objectives: This study aimed to determine the rate and severity patterns of bronchopulmonary dysplasia (BPD) and identify antenatal and postnatal factors associated with BPD in preterm infants <32 weeks of gestational age (GA). Methods: This retrospective observational study included preterm neonates <32 weeks of gestation admitted into the neonatal intensive care unit between January 2010 and December 2017 at Sultan Qaboos University Hospital, Muscat, Oman. A data set of antenatal and perinatal factors were collected. BPD was defined as the need for oxygen and/or respiratory support at 36 weeks post-menstrual age (PMA). Infants with and without BPD were compared in their antenatal and perinatal factors. Results: A total of 589 preterm infants <32 weeks were admitted. Among them, 505 (85.7%) survived to 36 weeks' PMA and 90 (17.8%) had BPD. The combined BPD and mortality rate was 28.4%. Grades 1, 2 and 3 BPD constituted 77.8%, 7.8% and 14.4%, respectively. BPD was associated with lower GA, lower birth weight, need for intubation at resuscitation, lower Apgar scores, longer duration of ventilation, surfactant therapy and higher rates of neonatal morbidities. On binary logistic regression analysis, predictors of BPD were longer duration of ventilation, intraventricular haemorrhage (IVH) and necrotising enterocolitis (NEC). Conclusion: In an Omani centre, 17.8% of preterm infants (<32 weeks GA) developed BPD. Various perinatal and neonatal factors were associated with BPD. However, longer duration of ventilation, IVH grades 1 and 2 and NEC stages II and III were significant predictors. Future multicentre research is necessary to provide the overall prevalence of BPD in Oman to help optimise the resources for BPD prevention and management in preterm infants.