What is the pipeline for future medications for obesity?

Obesity is a chronic disease associated with increased risk of obesity-related complications and mortality. Our better understanding of the weight regulation mechanisms and the role of gut-brain axis on appetite has led to the development of safe and effective entero-pancreatic hormone-based treatments for obesity such as glucagon-like peptide-1 (GLP-1) receptor agonists (RA). Semaglutide 2.4 mg once weekly, a subcutaneously administered GLP-1 RA approved for obesity treatment in 2021, results in 15-17% mean weight loss (WL) with evidence of cardioprotection. Oral GLP-1 RA are also under development and early data shows similar WL efficacy to semaglutide 2.4 mg. Looking to the next generation of obesity treatments, combinations of GLP-1 with other entero-pancreatic hormones with complementary actions and/or synergistic potential (such as glucose-dependent insulinotropic polypeptide (GIP), glucagon, and amylin) are under investigation to enhance the WL and cardiometabolic benefits of GLP-1 RA. Tirzepatide, a dual GLP-1/GIP receptor agonist has been approved for glycaemic control in type 2 diabetes as well as for obesity management leading in up to 22.5% WL in phase 3 obesity trials. Other combinations of entero-pancreatic hormones including cagrisema (GLP-1/amylin RA) and the triple agonist retatrutide (GLP-1/GIP/glucagon RA) have also progressed to phase 3 trials as obesity treatments and early data suggests that may lead to even greater WL than tirzepatide. Additionally, agents with different mechanisms of action to entero-pancreatic hormones (e.g. bimagrumab) may improve the body composition during WL and are in early phase clinical trials. We are in a new era for obesity pharmacotherapy where combinations of entero-pancreatic hormones approach the WL achieved with bariatric surgery. In this review, we present the efficacy and safety data for the pipeline of obesity pharmacotherapies with a focus on entero-pancreatic hormone-based treatments and we consider the clinical implications and challenges that the new era in obesity management may bring.

Role of ambient air pollution in asthma spread among various population groups of Lahore City: a case study.

Air pollution levels rise as a result of industrial and vehicular emissions, epidemiological issues such as asthma become more prevalent in Lahore, Punjab, Pakistan and cause adverse public health effects. Many studies explored the association between air pollutants and frequency of asthma hospital visits, although their effects are unclear. This study examined the link between air pollution, asthma, and socioeconomic and demographic factors. A questionnaire survey was administered among four age groups (15-25, 25-45, 45-60, and over 60 years old) in public and private hospitals of Lahore city. Daily average concentrations of five air pollutants including carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and particulate matter (PM2.5 and PM10) were recorded at ten fixed air monitoring sites in Lahore city. There were favorable connections between outpatient department (OPD) asthma visits (64%) and levels of outdoor air quality during winter season throughout the study period. The correlation between 1, 29, and 370 asthma patients and average daily air pollution levels found that the condition was more prevalent in females (53%) than males (47%). There was a significant correlation between PM10 exposure and asthma OPD visits in the city (p 0.001), as well as the elevated PM10 levels were substantially linked with OPD asthma visits over the winter season in the city. The hazard index (HI) for all adult population was estimated 0.001132. The study's findings indicate that exposure to ambient air pollution is a significant predictor of asthma hospital visits, particularly among the elderly. Strategies can be developed by policymakers in response to the worrying situation of allergic disease asthma in industrial cities due to air pollution.

Global ecological niche conservatism and evolution in Olea species.

Background and Aims: Climate is an important parameter in delimiting coarse-grained aspects of fundamental ecological niches of species; evolution of these niches has been considered a key component in biological diversification. We assessed phylogenetic niche conservatism and evolution in 24 species of the family Oleaceae in relation to temperature and precipitation variables. We studied niches of 17 Olea species and 7 species from other genera of Oleaceae globally. Methods: We used nuclear ribosomal and plastid DNA to reconstruct an evolutionary tree for the family. We used an approach designed specifically to incorporate uncertainty and incomplete knowledge of species' ecological niche limits. We performed parsimony- and likelihood-based reconstructions of ancestral states on two independent phylogenetic hypotheses for the family. After detailed analysis, species' niches were classified into warm and cold niches, wet and dry niches, and broad and narrow niches. Key Results: Given that full estimates of fundamental niches are difficult, we explore the alternative approach of explicit incorporation of knowledge of gaps in the information available, which allows avoidance of overestimation of amounts of evolutionary change. The result is a first synthetic view of evolutionary dynamics of ecological niches and distributional potential in a widespread plant family. Temperate regions of the Earth were occupied only by lineages that could derive with cold and dry niches; Southeast Asia held species with warm and wet niches; and parts of Africa held only species with dry niches. Conclusions: High temperature in Lutetian (Oligocene) and low temperature in Rupelian (Eocene) with major desertification events play important role for niche retraction and expansion in the history for Oleaceae clades. Associations between environmental niche characteristics and phylogeny reconstruction play an important role in understanding ecological niche conservatism, the overall picture was relatively slow or conservative niche evolution in this group.

Spatial distribution and computational modeling for mapping of tuberculosis in Pakistan.

BACKGROUND: Tuberculosis (TB) like many other infectious diseases has a strong relationship with climatic parameters. METHODS: The present study has been carried out on the newly diagnosed sputum smear-positive pulmonary TB cases reported to National TB Control Program across Pakistan from 2007 to 2020. In this study, spatial and temporal distribution of the disease was observed through detailed district wise mapping and clustered regions were also identified. Potential risk factors associated with this disease depending upon population and climatic variables, i.e. temperature and precipitation were also identified. RESULTS: Nationwide, the incidence rate of TB was observed to be rising from 7.03% to 11.91% in the years 2007-2018, which then started to decline. However, a declining trend was observed after 2018-2020. The most populous provinces, Punjab and Sindh, have reported maximum number of cases and showed a temporal association as the climatic temperature of these two provinces is higher with comparison to other provinces. Machine learning algorithms Maxent, Support Vector Machine (SVM), Environmental Distance (ED) and Climate Space Model (CSM) predict high risk of the disease with14.02%, 24.75%, 34.81% and 43.89% area, respectively. CONCLUSION: SVM has a higher significant probability of prediction in the diseased area with a 1.86 partial receiver-operating characteristics (ROC) value as compared with other models.

Genome-environment association methods comparison supports omnigenic adaptation to ecological niche in malaria vector mosquitoes.

The concept of a fundamental ecological niche is central to questions of geographic distribution, population demography, species conservation, and evolutionary potential. However, robust inference of genomic regions associated with evolutionary adaptation to particular environmental conditions remains difficult due to the myriad of potential confounding processes that can generate heterogeneous patterns of variation across the genome. Here, we interrogate the potential role of genome environment association (GEA) testing as an initial step in building an understanding of the genetic basis of ecological niche. We leverage publicly available genomic data from the Anopheles gambiae 1000 Genomes (Ag1000g) Consortium to test the ability of multiple analytically unique GEA methods to handle confounding patterns of genetic variation, control false positive rates, and discern associations with broadly relevant climate variables from random allele frequency patterns throughout the genome. We found evidence supporting the ability of commonly implemented GEA methods to account for confounding patterns of spatial and genetic variation, and control false positive rates. However, we fail to find evidence supporting the ability of GEA tests to reject signals of adaptation to randomly simulated environmental variables, indicating that discerning between true signals of genome environment adaptation and genome environment correlations resulting from alternative evolutionary processes, remains challenging. Because signals of environmental adaptation are so diffuse and confounded throughout the genome, we argue that genomic adaptation to ecological niche is likely best understood under an omnigenic model wherein highly interconnected, genome-wide gene regulatory networks shape genomic adaptation to key environmental conditions.

Geographic potential of the world's largest hornet, Vespa mandarinia Smith (Hymenoptera: Vespidae), worldwide and particularly in North America.

The Asian giant hornet (AGH, Vespa mandarinia) is the world's largest hornet, occurring naturally in the Indomalayan region, where it is a voracious predator of pollinating insects including honey bees. In September 2019, a nest of Asian giant hornets was detected outside of Vancouver, British Columbia; multiple individuals were detected in British Columbia and Washington state in 2020; and another nest was found and eradicated in Washington state in November 2020, indicating that the AGH may have successfully wintered in North America. Because hornets tend to spread rapidly and become pests, reliable estimates of the potential invasive range of V. mandarinia in North America are needed to assess likely human and economic impacts, and to guide future eradication attempts. Here, we assess climatic suitability for AGH in North America, and suggest that, without control, this species could establish populations across the Pacific Northwest and much of eastern North America. Predicted suitable areas for AGH in North America overlap broadly with areas where honey production is highest, as well as with species-rich areas for native bumble bees and stingless bees of the genus Melipona in Mexico, highlighting the economic and environmental necessity of controlling this nascent invasion.

Organochlorine pesticides in the surrounding soils of POPs destruction facility: source fingerprinting, human health, and ecological risks assessment.

The elimination of persistent organic pollutants (POPs) obsolete pesticides stockpiles, particularly the organochlorine pesticides (OCPs), is one of the critical environmental issues faced by many developing countries. This pioneering study aimed to investigate the occurrence, source fingerprinting, human health, and ecological risks of OCPs in the surroundings of the lone POPs pesticide destruction facility in Pakistan. The ΣOCPs residual levels in soil ranged from 35.98 to 566.77 ng/g dry weight (dw), with a mean concentration of 174.42 + 111.62 ng/g (dw). The OCPs contamination levels in the soil followed the pattern as ΣHCHs > Σendrins > Σendosulfans > dieldrin > Σheptachlors > ΣDDTs > Σchlordanes > methoxychlor. The ΣHCHs residual concentrations were comparatively higher than the previous national and global soil studies. The recent accumulation of HCHs, DDTs, and heptachlor was observed in the study area as identified by ß-HCH/∑HCHs, (DDE + DDD)/ΣDDTs, heptachlor/Σheptachlor, and heptachlor exo-epoxide/heptachlor ratios. The OCPs' lifetime carcinogenic risk through ingestion, dermal, and inhalation exposure routes ranged from 1.65E-08 to 2.91E-07, whereas the noncarcinogenic hazard quotient (HQ) ranged from 9.12E-05 to 1.61E-03. The risk vulnerability among age groups was in the order: adult > toddler > child > teen > infant. The calculated risk levels were within an acceptable limit of one in a million (1 × 10-6) for carcinogenic risk and HQ < 1 for noncarcinogenic risk. The current OCPs residual levels, especially dieldrin and endrin, exhibited low to medium ecological risks when compared to various worldwide limits. The upsurge of the OCPs' environmental contamination levels over the years and consideration of the food chain transfer might amplify the human health and ecological risks intensities.

Co-solubilization of polycyclic aromatic hydrocarbon mixtures in aqueous micellar systems and its correlation with FRET for enhanced remediation processes.

Surfactant enhanced remediation (SER) is an effective approach for decontaminating the PAH polluted soils. Solubilization and Cosolubilization of Phenanthrene (Ph), Pyrene (Py) and Perylene (Pe) as single, binary and ternary mixtures have been studied employing cationic (CTAB), anionic (SDS), non-ionic surfactant (Brij 30) and block copolymer (P123) micelles. In the single solute solubilization studies, solubility of Pe follows the order Brij 30 > CTAB > SDS whereas Ph or Py followed the order of CTAB > Brij 30 > SDS. In the cosolubilization studies, an increase, decrease or no change in the mutual solubility of PAHs was observed. Synergism in solubilization was observed most in P123 in both binary and ternary PAH mixture where more PAHs could get solubilized in the dense micellar shell region, thereby enhancing the micellar core volume leading to enhanced solubilization of PAHs. The solubilizates as pairs (Ph-Pe and Py-Pe) were further tested for any possible energy transfer in presence of surfactant based restricted host environments using spectrofluorometry and spectrophotometry. Based on the solubilization and cosolubilization an efficient non-radiative energy transfer (FRET) was observed between Ph/Py (donor) and Pe (acceptor) in the non-ionic surfactant system as well as in CTAB-Brij 58 mixed system. The results of this work may improve the effective utilization of surfactants in their correct evaluation for the removal of PAHs from contaminated soils or aquifers treated with SER technology.

Impacts of climate change on Capparis spinosa L. based on ecological niche modeling.

Recent changes in climate are transforming the situation of life on Earth, including impacting the conservation status of many plant and animal species. This study aims to evaluate potential impacts of climate change on a medicinal plant that is known to be heat-tolerant, Capparis spinosa L. We used ecological niche modeling to estimate current and future potential distributions for the species, considering two emissions scenarios and five climate models for two time periods (2050 and 2070). The results in terms of areal coverage at different suitability levels in the future were closely similar to its present-day distribution; indeed, only minor differences existed in highly suitable area, with increases of only 0.2-0.3% in suitable area for 2050 and 2070 under representative concentration pathway 4.5. Given that climate-mediated range shifts in the species are expected to be minor, conservation attention to this species can focus on minimizing local effects of anthropogenic activity.

Noise pollution in the hospital environment of a developing country: A case study of Lahore (Pakistan).

The present study investigates the noise pollution levels in public- and private-sector hospitals of Lahore. The noise pollution parameters were investigated from 20 public and 10 private hospitals. We observed that the equivalent continuous sound level (Leq) values varied significantly in different departments of the hospitals as well as at different times of the day. The public-sector hospitals had significantly higher noise pollution compared to the private-sector hospitals. The Wilcoxon Mann-Whitney two-sample rank-sum test revealed significant difference between noise levels in intensive care unit (ICU) during morning and in emergency, waiting area, intensive care unit (ICU), and reception during daytimes. However, no significant differences were found for any department during the evening. The Leq values were found to be higher than the international norms (WHO standards) for all hospitals, higher than USEPA for 29 hospitals and higher than local standards for 27 hospitals. Overall, significantly lower sound levels were always observed in private hospitals.

Assessing knowledge, performance, and efficiency for hospital waste management-a comparison of government and private hospitals in Pakistan.

Proper management of healthcare waste is a critical concern in many countries of the world. Rapid urbanization and population growth rates pose serious challenges to healthcare waste management infrastructure in such countries. This study was aimed at assessing the situation of hospital waste management in a major city of Pakistan. Simple random sampling was used to select 12 government and private hospitals in the city. Field visits, physical measurements, and questionnaire survey method were used for data collection. Information was obtained regarding hospital waste generation, segregation, collection, storage, transportation, and disposal. Data envelopment analysis (DEA) was used to classify the hospitals on the basis of their relative waste management efficiencies. The weighted average total waste generation at the surveyed hospitals was discovered to be 1.53 kg/patient/day of which 75.15% consisted of general waste and the remaining consisted of biomedical waste. Of the total waste, 24.54% came from the public hospital and the remaining came from the private hospitals. DEA showed that seven of the surveyed hospitals had scale or pure technical inefficiencies in their waste management activities. The public hospital was relatively less efficient than most of the private hospitals in these activities. Results of the questionnaire survey showed that none of the surveyed hospitals was carrying out waste management in strict compliance with government regulations. Moreover, hospital staff at all the surveyed hospitals had low level of knowledge regarding safe hospital waste management practices. The current situation should be rectified in order to avoid environmental and epidemiological risks.

Hydrogels of sodium alginate in cationic surfactants: Surfactant dependent modulation of encapsulation/release toward Ibuprofen.

The interaction of cetyltrimethylammoium bromide (CTAB) and its gemini homologue (butanediyl-1,4-bis (dimethylcetylammonium bromide), 16-4-16 with biocompatible polymer sodium alginate (SA) has been investigated in aqueous medium. Addition of K2CO3 influences viscoelastic properties of surfactant impregnated SA via competition between electrostatic and hydrophobic interactions. Viscosity of these polymer-surfactant systems increases with increase in concentration of K2CO3, and a cryogel is formed at about 0.5M K2CO3 concentration. The thermal stability of gel (5% SA+0.5M K2CO3) decreases with increase in surfactant concentration, a minimum is observed with increase in 16-4-16 concentration. The impact of surfactant addition on the alginate structure vis-à-vis its drug loading capability and release thereof was studied using Ibuprofen (IBU) as the model drug. The hydrogel with 16-4-16 exhibits higher IBU encapsulation and faster release in comparison to the one containing CTAB. This higher encapsulation-cum-faster release capability has been related to micelle mediated solubilization and greater porosity of the hydrogel with gemini surfactant.

An inhibitory effect of self-assembled soft systems on Fenton driven degradation of xanthene dye Rhodamine B.

Rhodamine B (RhB) is known to be a common organic pollutant despite having various technical applications. Treatment of effluents containing such compounds is important so as to minimize their effect on environment. Advanced Oxidation Processes (Fenton and Fenton like reactions) are such methods that can oxidize the contaminants powerfully and non-selectively. This work investigates the oxidation kinetics of dye RhB by hydroxyl radical (OH) generated via Fenton reaction in presence of surfactant assemblies of varying architectures using spectrophotometric, spectrofluorometic and tensiometric methods. The presence of surfactants viz. cationics, non-ionics and some binary mixtures in the pre-micellar and post micellar concentration ranges were found to inhibit the degradation of RhB to a varying degree. However, the reaction was totally inhibited in anionic surfactant. The experimental data was fitted to a pseudo first order kinetic model and the kinetic parameters obtained thereof were explained on the basis of the nature and type of interaction between the cationic form of RhB and the surfactants of varying architectures. The work has a critical significance in view of the fact that degradation studied in presence of surfactant assemblies is more representative than studied in aqueous solution because such conditions compare well with the conditions prevailing in the environment.