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Artificial intelligence (AI) encompasses a broad spectrum of techniques that have been utilized by pharmaceutical companies for decades, including machine learning, deep learning, and other advanced computational methods. These innovations have unlocked unprecedented opportunities for the acceleration of drug discovery and delivery, the optimization of treatment regimens, and the improvement of patient outcomes. AI is swiftly transforming the pharmaceutical industry, revolutionizing everything from drug development and discovery to personalized medicine, including target identification and validation, selection of excipients, prediction of the synthetic route, supply chain optimization, monitoring during continuous manufacturing processes, or predictive maintenance, among others. While the integration of AI promises to enhance efficiency, reduce costs, and improve both medicines and patient health, it also raises important questions from a regulatory point of view. In this review article, we will present a comprehensive overview of AI’s applications in the pharmaceutical industry, covering areas such as drug discovery, target optimization, personalized medicine, drug safety, and more. By analyzing current research trends and case studies, we aim to shed light on AI’s transformative impact on the pharmaceutical industry and its broader implications for healthcare.

Melatonin’s antioxidant properties make it a valuable component in anti-aging semisolid topical products. This study explores the role of Pemulen®, an acrylic-based viscosifying agent, in stabilizing cream-gel formulations. Remarkably, even at low concentrations (0.4%), Pemulen® successfully produced physicochemical stable topical formulations. In this work, the impact of the ratio of the oily phase—comprising olive oil and isopropyl myristate from 0 to 20%—was investigated to understand the internal microstructure effect on skin permeability, rheological properties, and stability. The formulations exhibited pseudoplastic behavior, with a significant positive correlation (p-value < 0.1) between the oily phase ratio, viscosity, spreadability, skin adhesiveness, and permeability. Formulations without the oil phase exhibited greater skin permeability. However, higher oily phase content enhanced viscosity, spreadability, and skin adhesion. Given that melatonin primarily degrades through oxidation, incorporating antioxidant excipients in semisolid formulations is crucial for maintaining its chemical stability. A quality by design (QbD) approach was used to assess the impact of four excipients—(a) DL-α-tocopheryl acetate (0.05%), (b) ascorbic acid (0.1%), (c) ethylene diamine tetraacetic acid (0.1%), and (d) sodium metabisulphite (0.5%)—on melatonin’s stability. Our findings indicate that maintaining the physical stability of the formulation with a 20% oil phase is more critical for protecting melatonin from oxidation than merely adding antioxidant excipients.

Osteocytes play an important role as regulators of both osteoclasts and osteoblasts, and some proteins that are secreted from them play a role in bone remodeling and modeling. LPS affects bone structure because it is an inflammatory factor, despite verbascoside’s potential for bone preservation and healing. Osteocytes may also be involved in the control of the bone’s response to immunological changes in inflammatory situations. MLO-Y4 cells were cultured in either supplemented -MEM alone with a low serum to inhibit cell growth or media with LPS (10 ng/mL) and/or verbascoside (50 g/mL) to show the LPS effect. In our research, LPS treatment increased RANKL levels while decreasing OPG and RUNX2 expression. Treatment with verbascoside reduced RANKL expression. In our work, verbascoside increased the expression of OPG and RUNX2. In MLO-Y4 cells exposed to verbascoside, SOD, CAT, and GSH activities as well as the expression levels of bone mineralization proteins like PHEX, RUNX2, and OPG were all elevated.

İzmit Bay, a 50 km long inlet at the eastern end of the Marmara Sea, is crucial for the region’s economy, culture, and marine ecosystem. The bay’s water circulation regulates nutrient distribution, stratification, sedimentation, oxygen levels, heat, and pollution levels. It is also influenced by meteorological events, such as short-term moderate to strong wind conditions. This study investigated the sensitivity of İzmit Bay Water Circulation to wind speed, direction, and duration using the MITgcm model with Orlanski boundary conditions and process-oriented modeling. The simulations showed that under weak forcing conditions, seawater temperature, salinity, and stratification do not significantly vary. However, strong forcing and wind speeds (statistically defined by percentiles of observation data) of 4.9 m/s (75%), 6.7 m/s (90%), and 10.1 m/s (99%) generate significant mesoscale and sub-mesoscale processes, depending on the direction. Westerly component winds cause downwelling at the eastern coastline, while easterly component winds bring sub-surface water to the surface. Strong winds from N, NE, and E sectors lead to the rise in lower-layer waters in the western basin, forcing them to overflow through the Hersek Delta sill into the central basin. Overall, severe wind events greater than 4.9 m/s (75%) significantly affect the bay’s hydrography by transforming the upper layer, with a decrease in temperature up to 5 °C and an increase in salinity up to 10 ppt.

Background and Objectives: Vancomisin-resistant Enterococci (VRE), is a resistant microorganism that colonizes and causes infections in hospitalized patients. The aim of this study was to show the spread of vancomycin-resistant Enterococcus faecium (VREfm) step-by-step in all intensive care units, which started with the growth of VREfm on 2 December 2021 in the blood culture of a patient hospitalized in the anesthesia intensive care unit of our hospital and was found to have reached epidemic size in the surveys. Materials and Methods: Rectal swab samples were taken from all patients hospitalized in intensive care units, VRE colonization was determined, the VanA and VanB resistance genes associated with the vancomycin resistance of VREfm isolates were determined by PCR method, and clonal association analysis was performed by Arbitrarily Primed-PCR (AP-PCR) and PFGE (pulsed-field gel electrophoresis). Results: In our study, VRE were detected in 61 of 2601 rectal swab samples. In total, fifty-four (85.52%) of the VRE isolates were Enterococcus faecium, three (4.91%) was Enterococcus faecalis, three (4.91%) was Enterococcus gallinorum, and one (1.63%) was Enterococcus casseliflavus. It was determined that all of the 54 VREfm isolates, which were the most detected among all VRE isolates, carried the vanA gene. In the clonal association analysis of the isolates by AP-PCR and PFGE methods, it was found that they had 12 different genotypes, 48 of them were included in any cluster, the clustering rate was 88.8%, and the largest cluster was the genotype 1 cluster, with 36 isolates. Of the 54 patients with VREfm isolated recently, 18.51 percent of the clinical samples were isolated before the survey, and 9.25% were isolated after the survey. It was determined that 100% of VREfm isolates were resistant to ampicillin, levofloxacin, ciprofloxacin, high-level gentamicin, trimethoprimsulfamethoxazole, and teicoplanin, 7.4% to tigecycline, and 1.85% to linezolid. Conclusions: In our study, in the clonal association analysis performed by isolating VREfm in rectal swab samples, it was found that 88.8% of the samples were indistinguishably similar, and that the increase in the number of VREfm infections after the index case in our hospital was associated with the epidemic. VREfm infections cause long-term hospitalization, costs and also deaths, which shows the seriousness of the event, and the importance of the combination of epidemiological and molecular analysis in epidemic research.

Background and Objectives: Similar to diabetes, the presence of left ventricular (LV) diastolic function (DD) has been reported in various studies which were conducted with people with a diagnosis of an impaired fasting blood glucose (FBG). This study aimed to examine the effects of the fasting blood glucose (FBG) levels on the left atrial strain (LAS) estimated by two-dimensional echocardiography speckle tracking analyses in patients without known diabetes. Material and Methods: The study included 148 participants (74 female and 74 male) without a history of diabetes mellitus or chronic disease. The patients were divided into two groups as follows: individuals with an FBG < 100 mg/dL and those with an FBG between 100 and 125 mg/dL after at least 8 h of overnight fasting. According to these FBG levels, speckle tracking echocardiography (STE) measures were compared. Results: There was a significant decrease in the LA reservoir (52.3 ± 15 vs. 44.5 ± 10.7; p = 0.001) and conduit strain (36.9 ± 11.7 vs. 28.4 ± 9.7; p = 0.001) in the impaired FBG group. When the STE findings of both ventricles were compared, no significant difference was observed between the groups in right and left ventricular strain imaging. Conclusions: In the earliest stage of LVDD, changes in atrial functional parameters become particularly evident. Echocardiographic analyses of these parameters can help to diagnose and determine the degree of LVDD while the morphological parameters are still normal. The addition of LAS imaging to routine transthoracic echocardiography (TTE) studies in patients with an impaired FBG but without a DM diagnosis may be helpful in demonstrating subclinical LVDD or identifying patients at risk for LVDD in this patient group.

Objective: Here, we compared the impact of different polices on the epidemiology of Vancomycin-resistant Enterococcus faecium bloodstream infections (VRE-BSIs) in a tertiary care hospital including two hospital buildings (oncology and adult hospitals) in the same campus. Material and Methods: All patients who were hospitalized in high-risk units were screened weekly for VRE colonization via rectal swab between January 2006 and January 2013. After January 2013, VRE screening was only performed in cases of suspicion of VRE outbreak and during point prevalence studies to evaluate the epidemiology of VRE colonization. Contact precautions were in place for all VRE-positive patients. The incidence density rates of hospital-acquired (HA)-VRE-BSIs were compared between two periods. Results: While the rate of VRE colonization was higher in the second period (5% vs. 9.5% (p < 0.01) for the adult hospital, and 6.4% vs. 12% (p = 0.02 for the oncology hospital), there was no increase in the incidence rate HA-VRE BSIs after the cessation of routine rectal screening in either of the hospitals. Conclusion: Screening policies should be dynamic and individualized according to the epidemiology of VRE as well as the workforce and cost. Periodical rectal screening of VRE can be discontinued if suspicion of an outbreak can be carefully monitored.

3D printing technologies enable medicine customization adapted to patients’ needs. There are several 3D printing techniques available, but majority of dosage forms and medical devices are printed using nozzle-based extrusion, laser-writing systems, and powder binder jetting. 3D printing has been demonstrated for a broad range of applications in development and targeting solid, semi-solid, and locally applied or implanted medicines. 3D-printed solid dosage forms allow the combination of one or more drugs within the same solid dosage form to improve patient compliance, facilitate deglutition, tailor the release profile, or fabricate new medicines for which no dosage form is available. Sustained-release 3D-printed implants, stents, and medical devices have been used mainly for joint replacement therapies, medical prostheses, and cardiovascular applications. Locally applied medicines, such as wound dressing, microneedles, and medicated contact lenses, have also been manufactured using 3D printing techniques. The challenge is to select the 3D printing technique most suitable for each application and the type of pharmaceutical ink that should be developed that possesses the required physicochemical and biological performance. The integration of biopharmaceuticals and nanotechnology-based drugs along with 3D printing (“nanoprinting”) brings printed personalized nanomedicines within the most innovative perspectives for the coming years. Continuous manufacturing through the use of 3D-printed microfluidic chips facilitates their translation into clinical practice.

The TD-NMR technique mostly involves the use of T1 (spin-lattice) and T2 (spin-spin) relaxation times to explain the changes occurring in food systems. However, these relaxation times are affected by many factors and might not always be the best indicators to work with in food-related TD-NMR studies. In this study, the non-conventional TD-NMR approaches of Solid Echo (SE)/Magic Sandwich Echo (MSE) and Spin Diffusion in food systems were used for the first time. Soft confectionary gelatin gels were formulated and conventional (T1) and non-conventional (SE, MSE and Spin Diffusion) TD-NMR experiments were performed. Corn syrups with different glucose/fructose compositions were used to prepare the soft candies. Hardness, °Brix (°Bx), and water activity (aw) measurements were also conducted complementary to NMR experiments. Relaxation times changed (p < 0.05) with respect to syrup type with no obvious trend. SE/MSE experiments were performed to calculate the crystallinity of the samples. Samples prepared with fructose had the lowest crystallinity values (p < 0.05). Spin Diffusion experiments were performed by using Goldman–Shen pulse sequence and the interface thickness (d) was calculated. Interface thickness values showed a wide range of variation (p < 0.05). Results showed that non-conventional NMR approaches had high potential to be utilized in food systems for quality control purposes.

The roughness of a surface is a decisive parameter of a material. In rehabilitation of concrete structures, for example, it significantly affects the adhesion between the coating material and the base concrete. However, the standard measurement procedure in construction suffers from considerable disadvantages, which leads to the demand for more sophisticated methods. In a research project, we, therefore, developed a novel camera-based measurement system, which is customized to meet the prevailing requirements for practical use on construction sites. In this article, we provide an overview of the measurement system and present comprehensive examinations to evaluate the accuracy and to provide evidence of validity. First, we examined the accuracy of the system by empirically assessing both trueness and precision of measurements using three concrete specimens. Trueness was determined by comparing the surface measurements to those of a highly accurate microscope system, revealing RMSE values of around 40–50 µm. Precision, on the other hand, was assessed considering the scattering of the roughness measurements under repeat conditions, which led to standard deviations of less than 6 µm. Furthermore, to proof validity, a comparative study was conducted based on sixteen concrete specimens, which includes the sand patch method and laser triangulation as established roughness measurement methods in practice. The empirically determined correlation coefficients between all three methods were greater than 0.99, indicating extraordinarily high linear relationships. Among them, the greatest correlation was between the camera-based system and laser triangulation.

Global warming and altered precipitation patterns are predicted to intensify the water loss in semi-arid and arid regions, and such regions in Turkey will be particularly affected. Moreover, water abstraction, not least for irrigation purposes, is expected to increase markedly, posing major threats to the water balance of the lakes and thus their biodiversity. Among the closed basins in Turkey, the Burdur Closed Basin (BCB), located in the southwest of Turkey, is expected to be most affected. The BCB includes several types of aquatic ecosystems which support high biodiversity, including one Ramsar site, six Important Bird Areas, and a considerable richness of native and endemic fish species. Therefore, it is essential to analyze the potential environmental impacts of climate change and increased water abstraction on BCB lakes and their biotic communities. Here, we combined historical data on ecosystems as well as meteorological, remote sensing, and ground-truth data to analyze the changes in the temperature and precipitation of the BCB, water surface areas, and land use, as well as the potential effects on waterbird and fish communities. We calculated the water budget to elucidate water availability in the basin over the last few decades and predicted future conditions based on rainfall and temperature forecasts using climate models. The Standardized Precipitation–Evapotranspiration Index (SPEI) was used to relate the water surface area to precipitation and temperature change in the basin. Crop-farming irrigation in the BCB has increased notably since 2004, leading to intensive water abstraction from the lakes and their inflows, as well as from ground water, to meet the increased demand for irrigation. The water abstraction from the lakes, inflows to the lakes, and the groundwater in the basin has increased the water loss in the catchment substantially. Remotely sensed data on lake surface areas showed a major shrinkage of shallow lakes in the last 40 years. Moreover, the largest lake in the basin, Lake Burdur, lost nearly half of its surface area, which is worrisome since the shallower areas are the most suitable for supporting high biodiversity. Climate models (CNRM-ESM2-1GCM for temperature and GFDL-ESM4-GCM for precipitation) suggest that from 2070, the BCB will face long-term, moderate-to-severe dry periods. This, and the increased demand for water for irrigation, along with climate change, may accelerate the drying of these lakes in the near future with devastating effects on the lake ecosystems and their biodiversity.

Currently, there is an unmet need to manufacture nanomedicines in a continuous and controlled manner. Three-dimensional (3D) printed microfluidic chips are an alternative to conventional PDMS chips as they can be easily designed and manufactured to allow for customized designs that are able to reproducibly manufacture nanomedicines at an affordable cost. The manufacturing of microfluidic chips using existing 3D printing technologies remains very challenging because of the intricate geometry of the channels. Here, we demonstrate the manufacture and characterization of nifedipine (NFD) polymeric nanoparticles based on Eudragit L-100 using 3D printed microfluidic chips with 1 mm diameter channels produced with two 3D printing techniques that are widely available, stereolithography (SLA) and fuse deposition modeling (FDM). Fabricated polymeric nanoparticles showed good encapsulation efficiencies and particle sizes in the range of 50–100 nm. SLA chips possessed better channel resolution and smoother channel surfaces, leading to smaller particle sizes similar to those obtained by conventional manufacturing methods based on solvent evaporation, while SLA manufactured nanoparticles showed a minimal burst effect in acid media compared to nanoparticles fabricated with FDM chips. Three-dimensional printed microfluidic chips are a novel and easily amenable cost-effective strategy to allow for customization of the design process for continuous manufacture of nanomedicines under controlled conditions, enabling easy scale-up and reducing nanomedicine development times, while maintaining high-quality standards.

Whey-protein-isolate-based composite hydrogels with encapsulated black carrot (Daucus carota) extract were prepared by heat-induced gelation. The hydrogels were blended with gum tragacanth, pectin and xanthan gum polysaccharides for modulating their properties. 1H spin-lattice relaxation experiments were performed in a broad frequency range, from 4 kHz to 30 MHz, to obtain insight into the influence of the different polysaccharides and of the presence of black carrot on dynamical properties of water molecules in the hydrogel network. The 1H spin-lattice relaxation data were decomposed into relaxation contributions associated with confined and free water fractions. The population of the confined water fraction and the value of the translation diffusion coefficient of water molecules in the vicinity of the macromolecular network were quantitatively determined on the basis of the relaxation data. Moreover, it was demonstrated that the translation diffusion is highly anisotropic (two-dimensional, 2D).

The use of a compact set of climate change indexes enhances our understanding of the combined impacts of extreme climatic conditions. In this study, we developed the modified Climate Extremes Index (mCEI) to obtain unified information about different types of extremes. For this purpose, we calculated 10 different climate change indexes considering the temperature extremes, extreme precipitation, and moisture surplus and drought over the Europe–Mediterranean (EURO–MED) region for the 1979–2016 period. As a holistic approach, mCEI provides spatiotemporal information, and the high-resolution grid-based data allow us to accomplish detailed country-based and city-based analyses. The analyses indicate that warm temperature extremes rise significantly over the EURO–MED region at a rate of 1.9% decade−1, whereas the cold temperature extremes decrease. Extreme drought has a significant increasing trend of 3.8% decade−1. Although there are regional differences, extreme precipitation indexes have a significant increasing tendency. According to the mCEI, the major hotspots for the combined extremes are the Mediterranean coasts, the Balkan countries, Eastern Europe, Iceland, western Russia, western Turkey, and western Iraq. The decadal changes of mCEI for these regions are in the range of 3–5% decade−1. The city-scale analysis based on urbanized locations reveals that Fes (Morocco), Izmir (Turkey), Marseille and Aix-en-Provence (France), and Tel Aviv (Israel) have the highest increasing trend of mCEI, which is greater than 3.5% decade−1.

This study investigates the impacts of climate change on the hydrological response of a Mediterranean mesoscale catchment using a hydrological model. The effect of climate change on the discharge of the Alata River Basin in Mersin province (Turkey) was assessed under the worst-case climate change scenario (i.e., RCP8.5), using the semi-distributed, process-based hydrological model Hydrological Predictions for the Environment (HYPE). First, the model was evaluated temporally and spatially and has been shown to reproduce the measured discharge consistently. Second, the discharge was predicted under climate projections in three distinct future periods (i.e., 2021–2040, 2046–2065 and 2081–2100, reflecting the beginning, middle and end of the century, respectively). Climate change projections showed that the annual mean temperature in the Alata River Basin rises for the beginning, middle and end of the century, with about 1.35, 2.13 and 4.11 °C, respectively. Besides, the highest discharge timing seems to occur one month earlier (February instead of March) compared to the baseline period (2000–2011) in the beginning and middle of the century. The results show a decrease in precipitation and an increase in temperature in all future projections, resulting in more snowmelt and higher discharge generation in the beginning and middle of the century scenarios. However, at the end of the century, the discharge significantly decreased due to increased evapotranspiration and reduced snow depth in the upstream area. The findings of this study can help develop efficient climate change adaptation options in the Levant’s coastal areas.

Determining the roughness of technical surfaces is an important task in many engineering disciplines. In civil engineering, for instance, the repair and reinforcement of building component parts (such as concrete structures) requires a certain surface roughness in order to ensure the bond between a coating material and base concrete. The sand patch method is so far the state-of-the-art for the roughness measurement of concrete structures. Although the method is easy to perform, it suffers from considerable drawbacks. Consequently, more sophisticated measurement systems are required. In a research project, we developed a novel camera-based alternative, which comes with several advantages. The measurement system consists of a mechanical cross slide that guides an industrial camera over a surface to be measured. Images taken by the camera are used for 3D reconstruction. Finally, the reconstructed point clouds are used to estimate roughness. In this article, we present our measurement system (including the hardware and the self-developed software for 3D reconstruction). We further provide experiments to camera calibration and evaluation of our system on concrete specimens. The resulting roughness estimates for the concrete specimens show a strong linear correlation to reference values obtained by the sand patch method.

Convective scale processes and, therefore, thunderstorm-related hazards cannot be simulated using regional climate models with horizontal grid spacing in the order of 10 km. However, larger-scale environmental conditions of these local high-impact phenomena can be diagnosed to assess their frequency in current and future climates. In this study, we present a daytime climatology of severe thunderstorm environments and its evolution for a wide Euro-Mediterranean domain through the 21st century, using regional climate model simulations forced by Representative Concentration Pathway (RCP) 8.5 scenario. Currently, severe convective weather is more frequently favored around Central Europe and the Mediterranean Sea. Our results suggest that with a steady progress until the end of the century, Mediterranean coasts are projected to experience a significantly higher frequency of severe thunderstorm environments, while a slight decrease over parts of continental Europe is evaluated. The increase across the Mediterranean is mostly owed to the warming sea surface, which strengthens thermodynamic conditions in the wintertime, while local factors arguably keep the shear frequency relatively higher than the entire region. On the other hand, future northward extension of the subtropical belt over Europe in the warm season reduces the number of days with severe thunderstorm environments.

Although Corynebacterium striatum is part of the human flora, it has recently drawn attention both for its multidrug resistance and its role as an invasive infection/outbreak agent. This cross-sectional study aimed to determine the antimicrobial resistance and clonal relationships among C. striatum strains. In total, 81 C. striatum strains were identified using Phoenix-100TM (BD, Sparks, MD, USA). The antimicrobial resistance of the strains was determined using the Kirby−Bauer disk diffusion method. Clonal relatedness among the strains was performed via arbitrarily primed polymerase chain reaction (AP-PCR). All 81 C. striatum strains were resistant to penicillin, cefotaxime, ciprofloxacin, and tetracycline, but susceptible to vancomycin and linezolid. The resistance rates to gentamicin, erythromycin, and clindamycin were 34.6%, 79%, and 87.7% respectively. AP-PCR results showed no predominant clone among the C. striatum strains. Corynebacterium striatum is reportedly the cause of an increasing number of invasive infections/outbreaks. Moreover, treatment options are limited. The study showed that vancomycin, linezolid, and gentamicin can be selected for the empirical treatment of C. striatum infections. Although no single-clone outbreak was observed in our hospital, small clonal circulations were observed within some units, indicating cross-contamination. Therefore, a comprehensive infection control program is warranted in future.

Background: Chiari Type I malformation (CM-I) is defined as the migration of cerebellar tonsils from the foramen magnum in the caudal direction and is characterized by the disproportion of the neural structures. The aim of this study was to investigate the brain volume differences between CM-I patients and normal population using a comparative volumetric analysis. Methods: 140 patients with CM-I and 140 age- and sex-matched healthy controls were included in this study. The magnetic resonance imaging (MRI) data of both groups were analyzed with an automated MRI brain morphometry system. Total intracranial, cerebrum, cerebellum, brainstem, cerebrospinal fluid (CSF), and lateral ventricle volumes as well as cerebrum and cerebellum gray/white matter (GM/WM) volumes were measured. Statistical analysis was performed. Results: Both total CSF and lateral ventricle volumes and volume percentages (Pct) were found significantly higher in CM-I patients compared to the control group. However, there were significant decreases in cerebrum and cerebellum volume Pct in CM-I patients. Although there were no significant differences in cerebrum WM volumes and volume Pct, cerebrum GM volume Pct were found to be significantly lower in CM-I patients. Conclusions: Revealing the increased CSF and lateral ventricle volume, and volume Pct supported concomitant ventricular enlargement and hydrocephalus in some CM-I patients. Decreased cerebrum GM volume Pct compared to the control group might be the underlying factor of some cortical dysfunctions in CM-I patients.

The search for rational treatment of neuropsychiatric disorders began with the discovery of chlorpromazine in 1951 and continues to evolve. Day by day, new details of the intestinal microbiota⁻brain axis are coming to light. As the role of microbiota in the etiopathogenesis of neuropsychiatric disorders is more clearly understood, microbiota-based (or as we propose, “fecomodulation„) treatment options are increasingly discussed in the context of treatment. Although their history dates back to ancient times, the importance of psychobiotics and fecal microbiota transplantation (FMT) has only recently been recognized. Despite there being few preclinical and clinical studies, the evidence gathered to this point suggests that consideration of the microbiome in the treatment of neuropsychiatric disorders represents an area of significant therapeutic potential. It is increasingly hoped that such treatment options will be more reliable in terms of their side effects, cost, and ease of implementation. However, there remains much to be researched. Questions will be answered through germ-free animal experiments and randomized controlled trials. In this article, the therapeutic potential of microbiota-based options in the treatment of neuropsychiatric disorders is discussed in light of recent research.

Fluctuating asymmetry, the random deviation from perfect symmetry, is a widely used population-level index of developmental instability, developmental noise, and robustness. It reflects a population’s state of adaptation and genomic coadaptation. Here, we review the literature on fluctuating asymmetry of human populations. The most widely used bilateral traits include skeletal, dental, and facial dimensions; dermatoglyphic patterns and ridge counts; and facial shape. Each trait has its advantages and disadvantages, but results are most robust when multiple traits are combined into a composite index of fluctuating asymmetry (CFA). Both environmental (diet, climate, toxins) and genetic (aneuploidy, heterozygosity, inbreeding) stressors have been linked to population-level variation in fluctuating asymmetry. In general, these stressors increase average fluctuating asymmetry. Nevertheless, there have been many conflicting results, in part because (1) fluctuating asymmetry is a weak signal in a sea of noise; and (2) studies of human fluctuating asymmetry have not always followed best practices. The most serious concerns are insensitive asymmetry indices (correlation coefficient and coefficient of indetermination), inappropriate size scaling, unrecognized mixture distributions, inappropriate corrections for directional asymmetry, failure to use composite indices, and inattention to measurement error. Consequently, it is often difficult (or impossible) to compare results across traits, and across studies.