Front Line Research Articles

Venetoclax resistance in acute myeloid leukaemia-Clinical and biological insights.

Venetoclax, an oral BCL-2 inhibitor, has been widely incorporated in the treatment of acute myeloid leukaemia. The combination of hypomethylating agents and venetoclax is the current standard of care for elderly and patient's ineligible for aggressive therapies. However, venetoclax is being increasingly used with aggressive chemotherapy regimens both in the front line and in the relapse setting. Our growing experience and intensive research demonstrate that certain genetic abnormalities are associated with venetoclax sensitivity, while others with resistance, and that resistance can emerge during treatment leading to disease relapse. In the current review, we provide a summary of the known mechanisms of venetoclax cytotoxicity, both regarding the inhibition of BCL-2-mediated apoptosis and its effect on cell metabolism. We describe how these pathways are linked to venetoclax resistance and are associated with specific mutations. Finally, we provide the rationale for novel drug combinations in current and future clinical trials.

Deploying whole blood to the battlefield-The Israel Defense Forces Medical Corps initial experience during the 2023 war.

Military and prehospital medical organizations invest significant resources to advance the treatment of trauma patients aiming to reduce preventable deaths. Focus is on hemorrhage control and volume resuscitation with blood products, with adoption of Remote Damage Control Resuscitation (RDCR) guidelines. The Israel Defense Forces Medical Corps (IDF-MC) has been using tranexamic acid and freeze-dried plasma (FDP) as part of its RDCR protocol for more than a decade. In recent years, low-titer group O whole blood (LTOWB) has been integrated, on IDF evacuation helicopters and expanded to mobile ambulances, complementing FDP use in treating trauma patients in state of profound shock. During the war that erupted in October 2023, the IDF-MC made a decision to bring LTOWB forward, and to equip every combat brigade level mobile intensive care units with LTOWB, onboard armored vehicles. The goal was to make whole blood available as close as possible to the point of injury and within minutes from time of injury. We describe the IDF-MCs' efforts to bring LTOWB to the front lines and present four cases in which LTOWB was administered. All patients were young male, with significant blood loss following penetrating injuries. One patient died in the operating room, following hospital arrival and emergency thoracotomy. The others survived. Our initial experience with bringing LTOWB as close as possible to the point of injury during high intensity fighting is encouraging, showing patient benefit along with logistic feasibility. After action reports and data collection will continue.

On the Front Lines: Helping Military Spouses Thrive in Your Community

Knowing how to support military spouses in your service network can contribute to mission readiness, and help military spouses thrive in the communities you serve. This publication discusses military spouse demographics, military spouse employment, military spouse well-being including food security, financial security, and civilian community belonging, and employment resources and strategies to support military spouses. Written by Kristen Jowers and Martie Gillen, and published by the UF/IFAS Department of Family, Youth and Community Sciences, January 2024.

Farmers on the front line: Perceptions, practices and discrepancies from the Aral Sea's Karakalpakstan and Khorezm regions

AbstractUndesirable changes in surface water and groundwater resources and land quality for biophysical and institutional reasons will further endanger the livelihoods of people in Central Asia. The farmers' understanding of these problems and the adaptation and solution strategies they opt for are the critical variables in devising relevant policies. Our findings captured significant disparities between farmer‐perceived water shortages and officially documented water availability, as well as soil salinity discrepancies. Farmers' coping strategies, including crop alterations and water‐saving measures, often lead to trade‐offs, such as reduced crop yields. The study highlights the need to consider farmer perceptions and practices along with official data when designing policies. Effective policymaking must consider this dynamic interplay and the multifaceted challenges faced by farmers in these vulnerable Aral Sea regions.

Организация и деятельность эвакогоспиталя № 1614 в годы Великой Отечественной войны 1941–1945 гг.

In the article, based on archival records, memoirs and documents, periodical materials, as well as scientific literature, we tried to highlight the organization in the Dagestan ASSR of one of the largest evacuation hospitals of the People’s Commissariat of Health of the USSR No. 1614 during the Great Patriotic War, which received frontline status as the front line advanced to the borders of Dagestan in 1942 and the unfolding battle for The Caucasus. The selfless and heroic work of doctors and medical staff of the evacuation hospital to provide unin-terrupted qualified medical care to wounded soldiers and officers of the Soviet Army is characterized. The weighty assistance of the leadership of the DASSR, the Ministry of Health of the Republic in organizing the hospital, as well as the residents of Dagestan, who surrounded their defenders with attention and organized a patriotic initiative in the form of fundraising for the Republican Committee for Assistance to Wounded and Sick Soldiers, is considered.

Farnesoid X receptor mediates macrophage-intrinsic responses to suppress colitis-induced colon cancer progression.

Bile acids (BAs) affect the intestinal environment by ensuring barrier integrity, maintaining microbiota balance, regulating epithelium turnover, and modulating the immune system. As a master regulator of BA homeostasis, farnesoid X receptor (FXR) is severely compromised in patients with inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC). At the front line, gut macrophages react to the microbiota and metabolites that breach the epithelium. We aim to study the role of the BA/FXR axis in macrophages. This study demonstrates that inflammation-induced epithelial abnormalities compromised FXR signaling and altered BAs' profile in a mouse CAC model. Further, gut macrophage-intrinsic FXR sensed aberrant BAs, leading to pro-inflammatory cytokines' secretion, which promoted intestinal stem cell proliferation. Mechanistically, activation of FXR ameliorated intestinal inflammation and inhibited colitis-associated tumor growth, by regulating gut macrophages' recruitment, polarization, and crosstalk with Th17 cells. However, deletion of FXR in bone marrow or gut macrophages escalated the intestinal inflammation. In summary, our study reveals a distinctive regulatory role of FXR in gut macrophages, suggesting its potential as a therapeutic target for addressing IBD and CAC.

The role of non-governmental human rights organizations in ensuring the collection of evidence for the international criminal court in the context of the war in Ukraine

In Ukraine, starting from February 2022, every day servicemen of the Russian army commit crimes that are a direct violation of international humanitarian law, not only on the front line, but also in the depths of the country, in the central and western regions. The author of the article analyzes the procedure for pre-trial investigation of international criminal crimes and the role of non-governmental public human rights organizations in this process. In addition, the new functions assigned to NGOs as separate non-governmental human rights organizations that have been operating on the territory of Ukraine since the beginning of the full-scale invasion were considered. The legal mechanisms for the involvement of NGOs in the collection of evidence on the ground, as well as the possibility of taking into account the collected information by international justice bodies, were studied. Specific examples and initiatives of the public sector, within the scope of the issue being studied, are given, and the functions, competences, and opportunities for increasing the effectiveness of NGO activity in the conditions of war are defined.
 It was concluded that non-governmental organizations, including human rights organizations, during the war in Ukraine discovered new areas of work and expanded the possibility of cooperation with state bodies. In turn, law enforcement agencies have provided access to limited information for the NGOs themselves by internal orders, which together increases the effectiveness of the pre-trial investigation of committed crimes. Thanks to this, feedback has been established. Special attention should be paid to the work of foreign NGOs and volunteers, which contributes to the recording of war crimes and crimes against humanity, which current Ukrainian refugees witnessed or became victims of.
 It was concluded that the main areas of evidence-gathering NGO activity are the following: 1) dissemination of information in the mass media about the condition of refugees who suffered as a result of the crimes of the Russian military, documenting the stories of witnesses of such offenses. In particular, the facts of torture and sexual violence (from the testimonies of refugees from Ukraine) were reported by the mass media in many European countries and beyond; 2) provision of advisory assistance regarding high-quality recording of episodes of criminal acts in order to recognize such evidence as appropriate; 3) peaceful gatherings and protests of public organizations, the active public against Russia’s war crimes in Ukraine, which, of course, is of great importance for the international community to recognize their severity and massiveness.
 It was concluded that the wide international recognition of the war crimes of the Russian Federation creates opportunities for the successful initiation of the International Tribunal or other judicial formats (such as the International Criminal Court, the Extraordinary Chamber) to bring the perpetrators to justice. All international actors collect evidence according to the clear requirements and standards of the International Criminal Court, and subsequently either transfer it to it or accumulate it in the prosecutor’s offices of certain countries for further referral to a designated responsible judicial body.

ТЕМАТИЧНА ПАРАДИГМА НОВИННИХ ПРОГРАМ РЕГІОНАЛЬНИХ ТЕЛЕКАНАЛІВ В УМОВАХ РОСІЙСЬКО-УКРАЇНСЬКОЇ ВІЙНИ

<p><strong><em>The purpose of the study</em></strong><em> is to point out the thematic specifics of the content of news programs on regional TV channels.</em></p><p><strong><em>Research methodology</em></strong><em>. The study used general scientific methods of analysis and generalization. The main method is content analysis, and monitoring and comparison methods were also used. The article is devoted to the study of the thematic paradigm of the news programs of the regional TV channels «Channel 12» (Lutsk), «STS» (Sumy), «Grad» (Odesa), «MTM» (Zaporizhzhia) in the context of the Russian-Ukrainian war. The empirical base consists of 120 news releases of the selected channels aired from 01.06.2023 to 30.06.2023.</em></p><p><strong><em>The results.</em></strong><em> The relevance of the study is due to the need to identify the leading topics on each of the selected TV channels, as well as their deviation from the dominant model, which is dominated by: reports of the Armed Forces of Ukraine on the state of events on the front lines, stories of IDPs, criminal chronicles, social issues of the region, volunteer initiatives, medicine, sports competitions and cultural events. The study found that during the war, the popularity of regional media in Ukraine increased significantly. The war and the socio-economic situation in the country led to the reformatting of the media space, which affected the topics of news programs on regional TV channels. The study found that during the war, the popularity of regional media in Ukraine increased significantly. The war and the socio-economic situation in the country led to the reformatting of the media space, which affected the topics of news programs on regional TV channels. Through quantitative analysis of news stories on the prevalence of certain topics in the newscasts, it is proved that stories on criminal and social issues were most often broadcast on Channel 12 and MTM, while on Grad TV channel information about reports of the Armed Forces of Ukraine and videos about culture prevailed, and the thematic content of the newscasts of STS mainly concerns social issues of the region and medicine. </em></p><p><strong><em>Novelty </em></strong><em>of the study lies in the attempt to scientifically outline the peculiarities of the topics of news stories on Ukrainian regional channels during Russia's full-scale invasion of Ukraine.</em></p><p><strong><em>The practical significance</em></strong><em> of the study lies in the possibility of applying the results obtained to improve and enhance the thematic content of news programs on regional TV channels.</em></p><p><strong><em>Key words: </em></strong><em>regional television, TV channel, audience, news story, thematic content, media space, news journalism, media market.</em></p>

Non-responders to neoadjuvant chemotherapy in pancreatic adenocarcinoma: Characteristics and outcomes.

662 Background: For patients with localized pancreatic adenocarcinoma, resection and systemic therapy remain the mainstays of curative-intent treatment. Neoadjuvant chemotherapy has been frequently employed with the goals of addressing systemic disease early and improving patient selection for surgery. Those who do not respond to neoadjuvant therapy present a challenge with a lack of randomized data to aid in decision making. Here we sought to define the characteristics and outcomes of those patients to guide clinical practice. Methods: This was a single-institution retrospective cohort study using a prospectively maintained database of those diagnosed with pancreatic adenocarcinoma. Patients included in the study were those who received neoadjuvant chemotherapy. Non-responders were defined as those with both no radiographic and no biochemical response at the first re-assessment after initiation of therapy. Results: A total of 176 patients were identified who were treated with neoadjuvant chemotherapy with curative intent. Of those, 42 (23.8%) patients had no evidence of either radiographic or biochemical response. Of those patients, 14 were upfront resectable (33.3%) and 20 were borderline resectable (47.6%). An additional 8 (19%) were locally advanced. Most patients received FOLFIRINOX as a first line chemotherapy agent (n = 25, 59.5%). A total of 12 (28.6%) patients underwent neoadjuvant radiation therapy. A total of 19 (45.2%) proceeded to surgery and two of those were found to be unresectable at exploration, resulting in 17 (40.5%) who ultimately received curative-intent resection. Exactly half (n = 21) of the patients had their chemotherapy switched (CS). Of those who had CS, 11 (52.4%) had evidence of local tumor progression on their initial restaging scan compared to just 3 (14.3%) of those who did not (p = 0.02). Additionally, patients who had CS had higher incidence of vascular involvement on their initial scan (90.5% vs 52.3%, p = 0.051). A total of 6 (28.6%) who underwent CS had subsequent biochemical response compared 4 (19.0%) of those who did not. Ultimately, 6 (28.6%) of those who had CS ultimately proceeded to surgery compared to 13 (61.9%) of those who did not (p = 0.062). Interestingly, there was no significant difference in median overall survival between those who had CS (18.6 months) and those who did not (19.9 months, p = 0.525). Conclusions: Non-responders to frontline neoadjuvant systemic therapy present a clinical challenge and have poor rates of curative-intent resection. Chemotherapy switch was employed mostly in cases with worse prognostic factors and thus infrequently lead to resection. Despite this, patients who underwent CS had similar overall survival to those who did not. These data suggest there may be a role for chemotherapy switch in those who do not respond to front line chemotherapy.

A novel avian intestinal epithelial cell line: its characterization and exploration as an in vitro infection culture model for Eimeria species

BackgroundThe gastrointestinal epithelium plays an important role in directing recognition by the immune system, and epithelial cells provide the host's front line of defense against microorganisms. However, it is difficult to cultivate avian intestinal epithelial cells in vitro for lengthy periods, and the lack of available cell lines limits the research on avian intestinal diseases and nutritional regulation. Chicken coccidiosis is a serious intestinal disease that causes significant economic losses in the poultry industry. In vitro, some cell line models are beneficial for the development of Eimeria species; however, only partial reproduction can be achieved. Therefore, we sought to develop a new model with both the natural host and epithelial cell phenotypes.MethodsIn this study, we use the SV40 large T antigen (SV40T) gene to generate an immortalized cell line. Single-cell screening technology was used to sort positive cell clusters with epithelial characteristics for passage. Polymerase chain reaction (PCR) identification, immunofluorescence detection, and bulk RNA sequencing analysis and validation were used to check the expression of epithelial cell markers and characterize the avian intestinal epithelial cell line (AIEC). AIECs were infected with sporozoites, and their ability to support the in vitro endogenous development of Eimeria tenella was assessed.ResultsThis novel AIEC consistently expressed intestinal epithelial markers. Transcriptome assays revealed the upregulation of genes associated with proliferation and downregulation of genes associated with apoptosis. We sought to compare E. tenella infection between an existing fibroblast cell line (DF-1) and several passages of AIEC and found that the invasion efficiency was significantly increased relative to that of chicken fibroblast cell lines.ConclusionsAn AIEC will serve as a better in vitro research model, especially in the study of Eimeria species development and the mechanisms of parasite–host interactions. Using AIEC helps us understand the involvement of intestinal epithelial cells in the digestive tract and the immune defense of the chickens, which will contribute to the epithelial innate defense against microbial infection in the gastrointestinal tract.Graphical

Conflicting demands and emotional labour: Balancing and swapping at the front line of the welfare state

This article combines insights from the sociology of emotional labour with works on conflicting demands facing employees to analyse how frontline staff conduct emotional labour in contexts marked by multifaceted demands facing them. It demonstrates the usefulness of this combination through an analysis of group interviews with frontline staff within Danish job centres, who are currently explicitly instructed to display sincere belief in the job prospects of clients, while also representing a disciplining activation system marked by conditionality. The article contributes to existing literature through an elaboration of two concepts – ‘balancing’ and ‘swapping’ – describing forms of emotional labour conducted by frontline staff in a work setting characterized by conflicting demands. The former is about striking a balance between the wants of the client and the wants of the system while sustaining clients’ feelings of motivation. The latter is about enabling oneself to encounter clients in ways which are personalized and informal, within the contours of a system marked by bureaucratic logics and language.

Soviet Diplomacy and Intelligence Efforts to Facilitate Finland’s Withdrawal from the 1941– 1944 War: Insights from Russian Archive

Through both intelligence channels and foreign policy efforts, Moscow gathered information in early 1941 about the growing alliance between Berlin and Helsinki, including increased German-Finnish military collaboration, the deployment of German troops and military equipment in Finland, the recruitment of Finnish volunteers for SS units in Germany, the construction of fortifications along the Soviet border, and the massing of Finnish forces near the Soviet frontier. Despite initially maintaining neutrality after Germany's invasion of the USSR, Finland declared war on the Soviet Union on June 26, 1941. The initial phase of the Soviet-Finnish front from July to December 1941 saw military successes favoring Finland. Subsequently, from late December 1941 until summer 1944, a "positional war" ensued with little change to the front line. During this period, Stockholm emerged as a key geopolitical hub where Soviet diplomats, led by A. Kollontai, and intelligence officers navigated the complex task of encouraging Finland to engage in peace talks with the Soviet Union and withdraw from the war. Sweden's neutrality in the conflict and its traditionally strong ties with Finland positioned it as an effective mediator in these negotiations. Additionally, Moscow successfully lobbied Washington to apply diplomatic pressure on Helsinki to initiate negotiations, which gradually began to yield positive results. The multifaceted efforts of Soviet diplomats and intelligence, coupled with A. Kollontai’s active involvement in this diplomatic endeavor, facilitated two rounds of Soviet-Finnish negotiations in Moscow in March and September 1944. While the March talks faltered due to Finnish delegates and political stances, the September negotiations succeeded in persuading Finland to agree to a truce, ceasing hostilities. This diplomatic victory contributed to the gradual disintegration of the anti-USSR coalition led by Germany, with Finland becoming a crucial component to exit this alliance.

Impact of Front Line Demonstrations on the pulses and oilseed productivity in South Tripura district

Krishi Vigyan Kendra, South Tripura undertaken number of front line demonstration (FLD) to impart knowledge on different improved scientific technologies of non-traditional oilseeds and pulses crops like groundnut, lentil, red gram (arhar) and green gram (moong) during Kharif and Rabi season of 2009-10. To demonstrate the technology, six villages of South Tripura district of Tripura state were selected after assessment of the village through PRA method. Awareness programme were conducted in all villages. Farmers were trained on scientific cultivation practices of groundnut, lentil, red gram (Arhar) and green gram (Moong). Besides imparting training, printed leaflets on oilseed and pulses were distributed among the farmers. Field day programme was also conducted in the farmer’s field during field demonstration. Altogether 8 hectare area of oilseed and 5 ha area of pulses was covered under this programme. Improved varieties of groundnut (GG-20, GG-7 and TG-37A), lentil (WBL-58), green gram (HUM-16) and red gram (UPAS-120) were distributed among the farmers. Under this programme, most of the farmers obtained better yield of pulses and oilseeds as compared to local varieties and traditional method of cultivation. The yield percentage increased from 21.43 to 40 per cent in case of pulses, and 30.43 to 65.45 per cent in oilseed crops. Farmers earned up to Rs.31,100/ha by selling oilseed and up to Rs. 29,250/ha by selling pulses crops. The programme conducted by KVK, South Tripura succeeded to build the skills of farmers for expansion of pulses and oilseeds crops through number of knowledge management practices like group meetings, awareness programmes, trainings, demonstrations, field day, etc. Farmers of the neighbouring villages also participated in this programme and expressed their willingness to take up such crops under scientific methods in the next crop season.

Negotiated Pipelines to Screenwriting Work on The Black List

This article argues that media professionalization services and their customers negotiate the role of aspirants in media industries. Using the screenwriting website The Black List as a case study, this article analyzes the company’s history, interface, promotional materials, and reception, arguing that The Black List has sought to formalize and standardize the professionalization process for aspiring and professional screenwriters alike as part of a broader entrepreneurial effort to digitalize film development writ large, assessing the value of unproduced film projects according to a universal standard. For aspiring media producers, professionalization services like The Black List are not marginal players in media industries but rather the front lines in an ongoing debate about who has the right to make media. While services like The Black List offer users relatively low-risk means to seek professionalization, they also reproduce imbalanced concentrations of media power, often under the guise of democratizing media culture.

The Role of Good Corporate Governance on Hospital Performance During Covid-19

This study focuses on the role of corporate governance in mediating the relationship between the public sector, specifically government-owned hospitals, and financial performance during the Covid-19 pandemic. While there is existing research on corporate governance, there is limited attention given to the public sector and government hospitals in the context of the pandemic. The study highlights government hospitals as they are on the front lines of healthcare services during the pandemic and have experienced a significant influx of patients, particularly in Covid-19 referral hospitals. This has created financial challenges for hospitals, with increased workloads and disrupted cash flows. The objective of this study is to determine the extent to which corporate governance can help manage the financial difficulties faced by government hospitals during the pandemic. The findings of this research are expected to provide valuable insights for the government and hospital managers, aiding in the improvement of corporate governance and financial performance during emergencies such as the Covid-19 pandemic

Organization of fighter battalions and their activities during the Great Patriotic War

The article examines the organization of fighter battalions and their activities during the Great Patriotic War, as well as the role of the Soviet and party bodies in ensuring public security in the front line and in the rear areas of the USSR when using voluntary formations. The history of the creation and deployment of fighter battalions as effective forms of popular mobilization in the rear, for the effective fight against German intelligence, which intensified during the period of the enemy's offensive along the entire front line, has been revealed. The content of organizational and pedagogical technology for training the distribution of workers in deficient professions and specialties in the school system of factory apprenticeships has been revealed. The directions and content of the ideological work of the state, focused on the working people of the rear, have been examined. The problemthematic field of this article has been investigated both using the information array of the central authorities and using the historiographic material of the local territorial-administrative unit of the former USSR - the South Osetian Autonomous Region. The problem-thematic field addressed in this article was examined not only based on data from central government bodies, but also for the first time using historiographical materials from the central archive of South Ossetia - a territorial-administrative unit of the former USSR.

Genetic mixing and demixing on expanding spherical frontiers.

Genetic fluctuation during range expansion is a key process driving evolution. When a bacterial population is expanding on a 2D surface, random fluctuations in the growth of the pioneers at the front line cause a strong demixing of genotypes. Even when there is no selective advantage, sectors of low genetic diversity are formed. Experimental studies of range expansions in surface-attached colonies of fluorescently labelled micro-organisms have contributed significantly to our understanding of fundamental evolutionary dynamics. However, experimental studies on genetic fluctuations in 3D range expansions have been sparse, despite their importance for tumour or biofilm development. We encapsulated populations of two fluorescent Escherichia coli strains in inoculation droplets (volumes [Formula: see text] nl). The confined ensemble of cells grew when embedded in a hydrogel-with nutrients-and developed 3D colonies with well-defined, sector-like regions. Using confocal laser scanning microscopy, we imaged the development of 3D colonies and the emergence of sectors. We characterized how cell concentration in the inoculation droplet controls sectors, growth rate, and the transition from branched colonies to quasi-spherical colonies. We further analysed how sectors on the surface change over time. We complement these experimental results with a modified 3D Eden growth model. The model in 3D spherical growth predicts a phase, where sectors are merging, followed by a steady increase (constant rate), and the experimentally analysed sectors were consistent with this prediction. Therefore, our results demonstrate qualitative differences between radial (2D) and spherical (3D) range expansions and their importance in gene fixation processes.

Forgotten warriors: a history of women on the front line; The women behind the few: the Women's Auxiliary Air Force and British intelligence during the Second World War

Forgotten warriors: a history of women on the front line; The women behind the few: the Women's Auxiliary Air Force and British intelligence during the Second World War

A quality improvement program for managing clozapine-induced constipation in a long-term structured residential setting for persons with serious mental illness

ObjectivesThe goal of this quality improvement project (QIP) was to increase awareness of the serious medical consequences of clozapine-associated constipation to front line nursing staff and patients with schizophrenia. MethodsThe QIP was developed iteratively by psychiatric nurses, psychiatrists and pharmacists with input from patients. The processes involved a literature review, development of educational materials for staff and patients, and the creation of a daily bowel movements log (BML). Implementation involved review of the BML at treatment team meetings, and deployment of pharmacological and non-pharmacological interventions to resolve constipation and increase awareness and knowledge of this clinical concern. OutcomesThe initial pilot screened for symptoms of constipation in patients receiving clozapine and non-clozapine antipsychotic agents and intervening as necessary during multidisciplinary team meetings. Patients benefited from relief of constipation and improved bowel habits. Staff benefited from improved knowledge and making requisite changes in workflow and practice. Feedback allowed refinements to be made to the educational materials for patients and staff. Since full implementation, bowel habits are routinely monitored, and interventions are reviewed for effectiveness. Staff satisfaction with this QIP is reflected in answers to a structured questionnaire and in patient reports (n = 50). ConclusionsClozapine, the only approved and efficacious medication for treatment-resistant schizophrenia is significantly underutilized. Medically consequential constipation can be a serious barrier to retention of patients benefiting from clozapine.Increased awareness and use of educational materials for patients and staff, routine monitoring of bowel habits combined with pharmacological and non-pharmacological interventions can successfully address this clinical problem.

Frontier Aspects of Genetics

In modern Science, the boundaries of a fragmented Description of Nature are like front lines, and the development of these Fragments of Science proceeds as if on a battlefield-who will displace whom. Whereas both the Unified Description of Nature and the correct Description of Fragments, as well as the same Genetics, must be sought on the path of establishing General INVARIANTS, which manifest themselves on the “front line”.