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Background There have been several destructive pandemic diseases in the human history. Since these pandemic diseases spread through human-to-human infection, a number of non-pharmacological policies has been enforced until an effective vaccine has been developed. In addition, even though a vaccine has been developed, due to the challenges in the production and distribution of the vaccine, the authorities have to optimize the vaccination policies based on the priorities. Considering all these facts, a comprehensive but simple parametric model enriched with the pharmacological and non-pharmacological policies has been proposed in this study to analyse and predict the future pandemic casualties. Method This paper develops a priority and age specific vaccination policy and modifies the non-pharmacological policies including the curfews, lockdowns, and restrictions. These policies are incorporated with the susceptible, suspicious, infected, hospitalized, intensive care, intubated, recovered, and death sub-models. The resulting model is parameterizable by the available data where a recursive least squares algorithm with the inequality constraints optimizes the unknown parameters. The inequality constraints ensure that the structural requirements are satisfied and the parameter weights are distributed proportionally. Results The results exhibit a distinctive third peak in the casualties occurring in 40 days and confirm that the intensive care, intubated, and death casualties converge to zero faster than the susceptible, suspicious, and infected casualties with the priority and age specific vaccination policy. The model also estimates that removing the curfews on the weekends and holidays cause more casualties than lifting the restrictions on the people with the chronic diseases and age over 65. Conclusion Sophisticated parametric models equipped with the pharmacological and non-pharmacological policies can predict the future pandemic casualties for various cases.

This paper presents a new approach for fabrication of single layer microbolometer detectors featuring pixel level vacuum packaging together with a lens on the pixel. The proposed lens structure can be used to increase the fill factor of the detector so that the pixel size can be decreased without decreasing the minimum feature size in the detector which is a problem in single layer microbolometers. The designs of the lens and the fabrication process of pixel level vacuum packaged microbolometer detector together with this lens are given in the framework of this study. The optical and mechanical simulations of the structure are performed. The radius of curvature of the lens is optimized to be 25 μm and it is shown that the condensing efficiency is 100% for 3 μm lens-detector distance. The deflection in the lens structure is found approximately as 0.8 nm in 1 atm environment pressure, showing that the proposed structure is durable. The proposed structure increases the fill factor to twice of the original value without decreasing the minimum feature size in the fabrication processes, resulting in the same amount of improvement in the performance of the detector. This approach can also be used to increase the yield and decrease the fabrication cost of single layer and also standard microbolometers with small pixel sizes, as it integrates the vacuum packaging in the fabrication steps.

De novo drug design has emerged as a valuable concept for the rapid identification of lead structure candidates. In particular, fragment-based molecular assembly methods have been successfully employed for the automated design of screening compounds. Here, we review the current status of these approaches, with an emphasis on adaptive techniques that can be used to artificially evolve novel bioactive molecules. Evolutionary algorithms (EAs) and particle swarm optimization (PSO) are presented as preferred techniques for iterative virtual synthesis and testing. By the inclusion of straightforward synthesis rules, druglike compounds can be obtained. Evolving compound libraries are particularly suited for hit and lead finding in situations where resources are limited and the complete testing of a large screening compound collection is prohibitive.

Peptic ulcer perforation (PUP) accounts for 5% of all abdominal emergencies and is recognized as a gastrointestinal emergency requiring rapid and efficient clinical evaluation and treatment. The mortality rate ranges from 10% to 40% among patients with perforation. In the present retrospective study, we examined the potential utility of the neutrophil-to-lymphocyte ratio (NLR) in early diagnosis of PUP; we asked whether this ratio allowed PUP and peptic ulcer disease to be distinguished. We enrolled the following patients: 58 with PUP, 62 with noncomplicated peptic ulcer diseases (NCPU), and 62 controls, between May 2010 and 2015. Patients who underwent surgical repair to treat PUP were included in the study group. Another group consisted of NCPU patients who had a noncomplicated peptic ulcer. The control group consisted of patients presenting with nonspecific abdominal pain to the emergency department. The mortality rate was 5.2% in the PUP group. The white blood cell count, C-reactive protein, and NLRs were higher in the PUP compared to the other groups (P<.001 for all). The white blood cell count and NLR did not differ between the NCPU and control groups. The sensitivities, specificities, positive predictive values, and negative predictive values of the NLRs were 68.0%, 88.0%, 82.9%, and 72.9%, respectively. We suggest that preoperative NLR aids in the diagnosis of PUP and can be used to distinguish this condition from peptic ulcer disease. Thus, the NLR should be calculated in addition to the clinical examination.

Key Points During the early phase of drug discovery, in silico receptor-based and ligand-based strategies are used to find novel hits. Pseudoreceptor models link the concepts of both strategies for utilization in virtual screening and quantitative structure–activity relationship modelling. Essentially, pseudoreceptor models can provide an entry point for receptor-based approaches for cases in which high-resolution structures of targets are lacking. The methodology of pseudoreceptor model generation involves three fundamental tasks. First, the presumed key interaction sites (anchor points) of the ligand–receptor complex are defined; second, the core pseudoreceptor model is assembled around these hypotheses; and last, model coordinates are optimized to gain more accurate calculated binding energies in validation studies. Molecular alignment of selected known actives represents the foundation of pseudoreceptor generation. Various approaches can be used to ensure that an optimized model is generated, and these include the use of reference compounds for which their binding mode is experimentally supported; use of key interacting groups; and use of ligands with high-affinity. Models can be generated and refined using various methods, and six main categories are discussed: grid-based, isosurface-based, partition-based, atom-based, peptide-based and fragment-based. Various case studies of pseudoreceptor modelling for hit and lead finding are described, including a pseudoreceptor model of sweet-tasting molecules, de novo design of non-steroid oestrogen receptor antagonists and investigation of ligand binding to a cocaine receptor. Although pseudoreceptor models can be very useful, it is important to realize their limitations. Most importantly, they do not represent real macromolecular binding sites, but only a model that is generated from known ligands. Nevertheless, as long as these limitations are kept in mind, they are an important tool in the drug discovery process. Pseudoreceptor models can provide a valuable tool for drug design in cases where a high-resolution structure of the target is not available. This article reviews pseudoreceptor modelling techniques, presenting recent applications in hit and lead finding, and critically discusses the prerequisites, advantages and limitations of the various approaches. Rational drug design is based on explicit or implicit structure–activity relationship models. Typically, receptor-based or ligand-based strategies are pursued, depending on the information available about known ligands and the receptor structure. Pseudoreceptor models combine the advantages of these two strategies and represent a unifying concept for both receptor mapping and ligand matching. They can provide an entry point for structure-based modelling in drug discovery projects that lack a high-resolution structure of the target. Here, we review the field of pseudoreceptor modelling techniques along with recent hit and lead finding applications, and critically discuss prerequisites, advantages and limitations of the various approaches.

The optimum biochemical or hematological marker to determine diagnosis and severity of acute diverticulitis has not been established. We aimed to compare the utility of hematological parameters in the diagnosis and severity of acute diverticulitis. Sixty-nine patients in diverticular disease (acute diverticulitis and diverticulosis subgroups) and 36 patients in control group were included in the study. The biochemical analysis performed at the time of diagnosis included white blood cell, mean platelet volume, neutrophil count, platelet count (PLT), C-reactive protein, and calculation of neutrophil count/lymphocyte and PLT/lymphocyte ratios. Patients in the diverticulitis group were divided into four stages according to the Hinchey classification based on abdominal CT findings. The mean platelet-lymphocyte ratio in the diverticulitis and diverticulosis groups was significantly lower than that in the control group (p<0.05). The best sensitivity and specificity values to distinguish acute diverticulitis and diverticulosis were 63.64% and 72.22% for the neutrophil-lymphocyte ratio (NLR) at a cutoff value of 2.78 and above and 30.30% and 86.11% for the platelet-lymphocyte ratio at a cutoff value of 87.46 and above. The diagnostic accuracy rates to distinguish between the diverticulitis and the control groups that the best sensitivity and specificity values were found to be NLR at a cutoff value of 11.55 and above and 100% and 100% for the platelet-lymphocyte ratio at a cutoff value of 12.28 and above. The NLR values were significantly lower in patients with Hinchey Stage 1 disease than those in patients with Stages 2 and 3 disease (respectively, p=0.003 and p=0.006). NLR and platelet-lymphocyte ratio can serve as useful biomarkers for the differential diagnosis and severity in acute diverticulitis.

Background : Acute appendicitis (AA) is one of the most common causes of emergent surgeries. Many methods are used for its diagnosis. Objectives : This study was conducted to investigate the diagnostic value of MPV and RDW in acute appendicitis. Patients and Methods : This study was a retrospective multi-center cross sectional planned study. The study included 260 patients operated for AA and 158 patients as the control group. Groups were compared in terms of MPV, RDW, white blood cell count (WBC), neutrophil predominance (NP) and platelet count (PC). Results : MPV was significantly lower in AA group, compared to the control group (P < 0.001). The best cut-off level for MVP in AA was ≤ 7.3 fL and the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy ratio were 45 %, 89.2 %, 87.3 %, 49.6 % and 61.7 %, respectively. There was no significant difference between the two groups in terms of RDW and platelet values. Conclusions : MPV is a routinely measured parameter in complete blood count (CBC) and requires no additional cost. It significantly decreased in AA, having a greater sensitivity and NPV when combined with WBC and NP.

Anastomotic leakages and adhesions after gastrointestinal tract surgery are still a significant cause of morbidity and mortality. The rate of anastomotic leakage is 3%-8%, whereas the mortality from leakage is over 30%. Intra-abdominal sepsis is a well-known cause of anastomotic leakage. In addition, intra-abdominal adhesion is a major cause of hospital admissions and reoperations and is associated with morbidity and mortality. In this study, we aimed to investigate the effects of a polyurethane membrane on anastomotic healing and intra-abdominal adhesions. This study used 32 Wistar albino rats divided into four groups. Standard resection of left colon 2 cm above the peritoneal reflection and colonic anastomosis were performed after causing abdominal sepsis through caecal ligation and perforation. The control groups (1 and 3) received no further treatment. The experimental groups (2 and 4) received the polyurethane membrane around the colonic anastomosis. Burst pressure, hydroxyproline, interleukin-6 (IL-6), nitric oxide (NO), tissue plasminogen activator (tPA), and tumor necrosis factor-alpha (TNF-α) levels were measured, and histopathological characteristics of the anastomosis were analyzed after re-laparotomy. Moreover, adhesion scores were measured. No statistically significant differences were found in the mean burst pressure levels between sacrificed animals on days three and five (p=0.259, p=0.177). When all the groups were compared, no significant difference was observed in the hydroxyproline, NO, and IL-6 levels (p=0.916, p=0.429, p=0.793, p=0.332, p=0.400, p=0.317). However, in groups 2 and 4, the tPA levels were significantly increased by Opsite therapy (p=0.001, p=0.003), and a statistically significant difference was observed in the adhesion scores (p<0.035). Groups 2 and 4 had significantly lower adhesion scores than groups 1 and 3. We found that Opsite therapy had no positive or negative effects on histopathological and biochemical healing in the experimental septic colon anastomosis model. However, the perianastomotic application of polyurethane membrane effectively decreased the intra-abdominal adhesions.

The control of port site bleedings (PSB) is particularly difficult in obese patients. PSB can lead to morbidity via inhibiting the minimally invasive features of laparoscopic surgery such as the increase in the incision size. PSB can be controlled by Foley catheter. PSB has been observed in four patients with body mass index >35 and the bleeding cannot be prevented with different hemostasis techniques (for instance cauterization, etc.). Bleeding can be controlled upon placing the Foley catheter and then the balloon was inflated and putting it to the traction in the port site. Umbilical cord clamp was used instead of traditional methods for traction. In addition to the hemostatic effect of traction, the effect of compression of the umbilical clamp contributed to hemostasis. Catheter was removed after 24-36 hours. Bleeding did not occur again upon the usage of Foley catheter in these patients. Foley catheter traction is an easy and efficient hemostatic technique in patients with PSB.

Objective: Acute appendicitis (AA) is one of the most common surgical emergencies. Despite extraordinary advances in modern investigations, the accurate diagnosis of AA remains an enigmatic challenge. The aim of this study was to compare and evaluate the diagnostic accuracy of inflammatory parameters [C-reactive protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR)], ultrasound (US) and Alvarado score (AS) in reducing the rate of negative appendectomies. Material and Methods: Two hundred seventy-eight patients were included in this study. Patients were separated into two main groups as the surgery group (n=184) and non-operative group (n=94). Complete blood count, ESR and PCT levels were assessed, abdominal US was performed and AS was calculated for all patients. Results: In the surgery group, clinical predictive factors for histopathologic results such as AS ≥7, AA signs on US, neutrophilia and leukocytosis were significant. Neutrophilia and leukocytosis had the highest accuracy rate among these factors. Inflammatory parameters were not predictive for histopathologic results, although higher CRP and PCT levels were significant in perforated and necrotizing appendicitis. Multifactorial regression analyses showed that AS was not of significant predictive value in the non-operative group. Conclusion: There was no superiority of AS and/or US in the diagnosis of AA. Recent findings have shown the most reliable parameters in the diagnosis of AA to be primarily 'neutrophilia' and secondarily 'leukocytosis'. Other results of this study indicated that inflammatory parameters (CRP, PCT, ESR) were not superior to other parameters but CRP and PCT levels were significantly high in complicated cases.