Depression impacts the lives and daily activities of millions globally. Research into the neurobiology of lateral habenula circuitry and the use of psychedelics for treating depressive states has emerged in the last decade as new directions to devise interventional strategies and therapies. Several clinical trials using deep brain stimulation of the habenula, or using ketamine, and psychedelics that target the serotonergic system such as psilocybin are also underway. The promising early results in these fields require cautious optimism as further evidence from experiments conducted in animal systems in ecologically relevant settings, and a larger number of human studies with improved spatiotemporal neuroimaging, accumulates. Designing optimal methods of intervention will also be aided by an improvement in our understanding of the common genetic and molecular factors underlying disorders comorbid with depression, as well as the characterization of psychedelic-induced changes at a molecular level. Advances in the use of cerebral organoids offers a new approach for rapid progress towards these goals. Here, we review developments in these fast-moving areas of research and discuss potential future directions. Depression affects millions of people worldwide. Analysis of the data collated by the World Health Organisation suggests that depression as a leading cause of disability has grown worldwide and in 2017 had more than 250 million sufferers, making it one of the most common mental ailments , substanIn recent times, there has also been an increasing appreciation for the dynamic nature of neural circuitry under duress and the potential role of neuroplasticity that becomes maladaptive in conditions like major depressive disorder (MDD) . This inInterestingly, a very different approach from that of targeting a specific brain region has reemerged in parallel in the search for an appropriate antidepressant treatment regimen . This reIn this article, we review recent developments in these two fast-moving areas of research and discuss the potential future directions that can bridge progress in both. The revival of interest in the habenula complex in the context of neuropsychiatric ailments has been fueled by the seminal work conducted by Matsumoto, Hikosaka, and colleagues that demonstrated the reward-prediction error function of lateral habenula . That is2+ responses of neurons revealed that a passive coping strategy was associated with progressive activation of neurons in the ventral habenula . Conversely, activation of ventral-habenula neurons using optogenetic manipulation, resulted in both behavioral passivity and suppression of the serotonergic neurons in the raphe [Malfunction in the reward processing and reinforcement behaviors are closely tied to many brain disorders including addiction and MDD . Consequhe raphe , thus cohe raphe . A wholehe raphe . A seriehe raphe ,60,61,62Preclinical animal models provide a valuable avenue to dissect a complex phenomenon such as depression and discover potential antidepressant treatments. In rodents, several phenotypes in specific behavioral tests have been used to model human depression, though not all of them may have a face, predictive, and construct validity, and the interpretation of the animal’s behavior in these tests has changed over time . Among tB receptors, regulated by the enzyme PP2A. An increase in the PP2A activity due to the shock paradigm increases the internalization of these proteins. Inhibition of PP2A, specifically in the lateral habenula, on the other hand, restores the currents from these channels and reverses both the effects on neuronal excitability, and the depressive-like behaviors exhibited [Another approach to target the lateral habenula hyperactivity has been the use of pharmacological aids. The two most notable examples are the administration of protein-phosphotase 2A (PP2A) inhibitors and ketamine. Mice experiencing inescapable shock develop depressive-like phenotypes and exhibit neuronal hyperactivity in the lateral habenula . The autxhibited . A pair of studies from the Hailan Hu lab has also charted out another physiological dysfunction in the lateral habenula and how ketamine rapidly reverses this deficit in rodent models to produce antidepressant effects ,14. KetaTargeting the hyperactivity of the lateral habenula, either through DBS or chemogenetic inhibitors , or by u3, accounting for only a few voxels in an fMRI image. This makes delineating the responses of these two distinct nuclei quite difficult [Human habenula studies have generally been in agreement with the findings in animals and non-human primates. Habenula activation was reported when there was a punishment prediction error, and in aversive events rather than in neutral or rewarding events ,68,69. Fifficult . Studiesifficult ,71. Contifficult . A seconWhat these results mean in the broader context of the research in this area needs further analysis. As the authors of these studies point out, caution is required when interpreting human studies of this kind and when comparing the results from animal studies. To draw robust conclusions on the role of the lateral habenula activity in MDD patients, at least four methodological refinements are necessary. First, fMRI resolution for structures as small as the habenula can be faulty even after careful quality control during registration. An exploration of new methods, such as those adapting computational geometry to compare spatiotemporal dissimilarities, may be needed for disambiguation . Better The use of animal models to dissect the underpinnings of human brain disorders is irreplaceable , yet stuThe second point of caution is with respect to the interpretation of results from the standard practice of activating or inactivating neurons to understand how their (in)operation affects specific aspects of a given behavior . Such stWhile such detailed investigations at the physiological level are essential to devise pharmacological interventions for depression, a complementary approach practiced to a lesser extent is to conceptualize the phenomena and related deficits more broadly. Depressive behaviors have been noted to be often comorbid with a few neuropsychiatric disorders ,3,5,6. SB receptors as the common substrate whose function is compromised [B receptor antagonists in general show antidepressant effects, while temporal lobe epilepsy patients with depression and anxiety show an increased expression of GABAB receptors as determined by autoradiography studies [ceftriaxone, an antibiotic known to increase GLT-1 expression, normalized the hyperactivity of lateral habenula neurons in slices, and reversed depression-like and anxiety-like behaviors in rats undergoing alcohol-withdrawal [One commonality between symptoms of different conditions could be the neuromodulator system impacted. A common substrate altered in depression, chronic pain, and insomnia for instance is the dopaminergic function. Its role in arousal has been hypothesized as the potential common factor for the high frequency of the concurrence of these three disorders, each likely exacerbating the symptoms of the other conditions . Anxietypromised ,86. GABA studies , which sthdrawal . The latthdrawal . The phythdrawal , new insescitalopram in an initial evaluation study of combining pharmacotherapy with CBT [Recognition of conditions where mental illnesses are comorbid with depression is also critical to improve the overall clinical outcomes. Preventive measures to counsel subjects who are at high risk for a second disorder when presenting symptoms of the first among comorbid disorders could enhance treatment objectives and subject well-being. Treatment of one of the comorbid diseases may have positive effects on the treatment of other diseases if a common element is targeted. For example, in a study where Cognitive Behavioral Therapy (CBT) was used to alleviate symptoms of social anxiety disorder, a decrease in depressive mood episodes was also reported . Similarwith CBT . More suIn the context of studying depressive states holistically, psychedelic research has resurfaced in the past few years as an important avenue to seek solutions, after decades of research attempts being stifled by regulatory constraints. The modern era of psychedelic research can be traced back to the well-documented discovery of the properties of the synthetic psychedelic lysergic acid diethylamide (LSD) in 1938 . After aAn important step has been the recognition of the potential of psychedelics in treatments beyond their use as a medication to reduce the despair and suffering of patients in palliative care coping with a terminal illness . For exaEach psychedelic has a different profile of effects with a fair degree of overlap ,92,93,94While the research on potential mechanisms and symptom-level explanations is being investigated actively, a new animal study coincidentally connects these findings in humans to the lateral habenula. A recent study that modeled treatment-resistant depression in rats used optogenetic manipulation to silence the activity of the lateral habenula and examined the rodent DMN using high-resolution rodent fMRI . This pe2a, to be the molecular target of psychedelics [Pharmacologically, both Psilocybin and LSD, and other molecules that act via the serotonergic system have been categorized as psychedelics ,101,102.hedelics . As poinhedelics , it has hedelics . As IEGShedelics . One way forward for this research is to use the “mini-brains” or cortical organoids that show complex cellular organization and physiological responses . CerebraThe use of the cerebral organoids to uncover the molecular mechanisms of psychedelic action overcomes many limitations imposed by the lack of appropriate animal models and regulatory restrictions ,110,111.Another promising direction anticipated in the antidepressant research is to derive organoids for use in precision medicine type studies and examine the potential effects of antidepressants in the context of individual risk variants and known genetic susceptibilities . They maLateral habenula is one of the most intensely researched brain regions currently to find remedies for treating depression and several comorbid neuropsychiatric disorders. Methodological refinements in human studies, alongside an expansion of the animal systems used to model depression, are necessary to understand the role of this brain region in these disorders. Studies that address the sparsity of models investigating the common underlying molecular factors in comorbid disorders have the potential for discovering new therapeutic approaches. At the same time, understanding the antidepressant mechanism of psilocybin and psychedelics warrants scientific priority as the use of these agents has the possibility of providing profound insights not only into how to “rewire” a brain in depression but also into the normal operation of brains. We think it will also reveal the exact nature of the connections between these two areas of research that appear to be emerging .


Preterm birth is a global health concern and continues to contribute to substantial neonatal morbidity and mortality despite advances in obstetric and neonatal care. The underlying aetiology is multi-factorial and remains incompletely understood. In this review, the complex interplay between the vaginal microbiome in pregnancy and its association with preterm birth is discussed in depth. Advances in the study of bacteriology and an improved understanding of the human microbiome have seen an improved awareness of the vaginal microbiota in both health and in disease. Trichomonas vaginalis and Chlamydia trachomatis have long been associated with increased risk of PTB, recent applications of molecular-based profiling methods have provided new insights into the role that microbe-host interactions in pregnancy play in shaping PTB risk ..LactobacLactobacillus LBP. L. crispatus has been shown to inhibit growth of Streptococcus agalactiae (group B streptoccocus) in vitro. In non-pregnant women with a history of recurrent urinary tract infection, vaginal administration of L. crispatus following antibiotic treatment showed effective vaginal colonisation and a reduction in urinary tract infection recurrence [L. acidophilus and L. rhamnosus combined and L. crispatus has been shown a significantly reduced risk of recurrence in BV [L. crispatus represents a promising approach for beneficial modulation of the vaginal microbiota in pregnancy.An alternative approach is direct vaginal administration of currence . Vaginalce in BV , 135. TrLactobacillus crispatus. This opens the door to modulation through the use of live bio-therapeutic products.The introduction of high-throughput DNA sequencing techniques into microbiological research has confirmed what was previously known from culture-based classical microbiology and greatly expanded our ability to study communities of microorganisms. Whilst it is doubtful that a physiologically essential placental microbiome exists, it remains possible that some cases of preterm labour may be due to haematogenous spread of organisms to the placenta and uterus. Studying the role of the gut microbiota in pregnancy and the potential for gut microbial inflammation to be linked to PTB risk will be challenging, but could potentially be paradigm changing. The strongest evidence for the role of the microbiome in preterm birth relates to the vaginal microbiota. But there remain significant geographical and ethnic differences, the underlying mechanisms of which are yet unknown and whose elucidation will provide valuable insights into the mechanisms of preterm birth in different ethnic groups and communities. The most consistent finding across almost all studies is the benefit of a vaginal microbiota characterised by


Relative to the other techniques, the dolphin kick without a diving gear demonstrated the highest vav and low SI and VIVIndex values, which reflects the most advantageous economy of propulsion at given velocity. Given the lack of statistical differences, using the breaststroke kick and flutter kick when swimming with a diving gear seems to be comparable to dolphin-kick in terms of average velocity and parameters reflecting the economy of propulsion. Thus, a search for fin swimming techniques with the aim of achieving specific goals seemed reasonable. The results suggest, that performance achieved while using various fin swimming techniques was probably controlled by different strategies of leg movements. These strategies revealed differences in a spatiotemporal (SR-SL) structure of the stroke and they were closely associated in terms of the velocity variation decrease.The aim of this study was to compare underwater fin swimming performance using dolphin, flutter and breaststroke kicks with and without diving gear. Performance was evaluated in terms of average swimming velocity. The parameters of spatiotemporal structure of the stroke reflecting to the swimming economy were employed. Conscious modifications in propulsion technique were considered here with the aim of controlling swimming performance. A total of ten professional scuba divers swam at maximal speed underwater for 50m using each of three techniques: dolphin, flutter, or breaststroke kicks. Swimmers’ performance was compared between holding their breath and using breathing apparatus. Two cameras recorded their movements in sagittal and transverse planes. The average swimming velocity (v Fin swimming is a widely practiced aquatic activity. The large surface of the fin facilitates propulsion in competitive fin swimming and underwater hockey. Fins are also used in recreational swimming and scuba diving. They often constitute part of the personal equipment of lifeguards and are basic equipment for industrial and military divers. Various goals are implemented within a broad spectrum of these activities. In competitive fin swimming, the specific skills and goals imply maximizing performance and rational energy expenditure, allowing maintenance it at stable levels over the entire distance . Lifeguaav) is the best measure of swimming performance. However, its significance is more pronounced while swimming at a short distance than at a longer one ; and SR, defined as the average number of strokes per time unit [1/s]. Next, the SI was calculated  were used to film all of the divers underwater  at a samlculated  accordinIndex) was also estimated (The index of variation of intracycle velocity (VIVstimated . This inav) was used in this study as one of the main contributing factors, which determines performance. As swimming speed increases, the hydrodynamic resistance that the swimmer must overcome also rises, thus creating an increase in energy cost. Thus, the economy of propulsion can be assessed at given swimming velocity [Index, which represents the criterion for minimization of drag by means of avoiding changes in intracycle velocity, can be perceived as a parameter revealing of the economization of propulsion utilization. Increases or decreases in swimming velocity are determined by combined increases or decreases in SF and SL, respectively [Measuring swimming speed is considered a simple way for assessing the performance . Therefovelocity . In thisvelocity , in accovelocity , SI can velocity  Thus theectively ,17,18. Tectively , 20–22.The displacement of the hip of each swimmer was also tracked in one swimming stroke in the following manner: the beginning and the end of the stroke were carefully estimated during a digital motion analysis mentioned earlier. In the dolphin-kick—from the highest heel position before downward phase, until the highest heel position after the upward phase; in the flutter-kick—in the same way as in the dolphin kick, but with one (more visible) leg; for the breaststroke—from the beginning of the initial phase (the first motion after straightening of the legs), through push-off until the end of the gliding phase with the legs straight (beginning of the next movement).The center of mass of the air tank was also estimated experimentally (on land). The fulcrum in which the horizontally positioned tank remained in equilibrium was found. The projection of this point was transferred onto the tank body (as a line). Then, at this line the half the transverse dimension of the air tank was estimated with a caliper. In this point the center of mass was marked. This marker was visible when the air tank was inside the buoyancy jacket.The estimated cross-sectional areas of the divers’ bodies when swimming with or without diving gear were compared . This esStatistical analyses were performed using Statistica 12.0 software . The raw statistical analysis of the described parameters facilitated 3x2 analysis of variance for dependent samples . The variables were introduced as two groups of qualitative predictors: propulsion generation techniques  and diving gear (swimming with and without equipment). The results obtained (the average margin) were normalized. The statistical significance of each difference was estimated by Duncan’s post-hoc test, thus creating a foundation for research on the dependencies between all of the parameters (Spearman’s rank correlation).av) swimming technique in both trials. In addition, the stroke index (SI) strongly differentiated this technique from the others in swimming without diving gear (Index) significantly differ from the other techniques.As shown in ing gear . Moreoveav and VIVIndex, while significant differences between the dolphin kick and the breaststroke kick were found in vav when swimming using diving gear. It should be emphasized that for swimming without diving gear, no significant differences in SI between flutter and breaststroke kicks were found. The same statistical sense was observed in the case of differences between all kicking techniques for swimming with diving gear.In the swimming trials without diving gear, all three leg-kicking techniques were significantly differentiated by vIn both trials (swimming with and without diving gear) for all three fin swimming techniques studied, statistically significant differences  were fouav), stroke index (SI) and the index of variation of intracycle velocity (VIVIndex) were significantly  and economization of generation (SI) and utilization (VIVIndex) of kicking propulsion and completeness of them, allow to exemplify the cause-effect mechanisms determining the optimal fin swimming performance while employing different kicking techniques.The results of Spearman’s rank correlation between the studied parameters  were anaav was observed. For breaststroke kicking, a lack of significant correlations was noted between: vav and SI, SL; VIVIndex and SR, SL, SI; SI and SR.In the trials performed without diving gear , an inveav) of dolphin and flutter kicking without diving gear increase together with the lengthening of SL (positive correlation) and with the minimization of the variation in intracycle velocity—VIVIndex (negative correlation), as shown in av. The high average swimming velocity (vav) of breaststroke kicking seemed to be the result of a minimization of VIVIndex. On the other hand, a reduction of the SR in correlation with a lengthening of SL probably indirectly implied a higher value of the SI (in terms of SL to vav ratio).The average swimming velocity (vav) of dolphin kicking probably resulted from minimizing the SI (SL to vav ratio) minimizing the VIVIndex, together with lengthening of the SL, associated with reduced SR. For flutter kicking, increased vav went hand in hand with reduced VIVIndex and increased SR. The SI and SL did not have an influence on vav. In breaststroke kicking the vav increased only as a consequence of proportional relationships between the lengthening of SL and increased SI. It should be emphasized that the set of correlations between parameters relating to swimming with diving gear were suggestively less completed than in trials without the gear.In the trials performed with diving gear , the higIt was revealed that the cross-sectional areas of the scuba divers’ bodies wearing the equipment were +44.6% larger than when swimming without the gear .The inertia forces generated as a consequence of displacement of the mass of the air tank, and its influence on the intracycle velocity variations in the swimmer's body and air tank system were also taken into investigation. The sample charts of the intracycle velocity variations of the divers’ bodies (hip joint) and the air tank in time function  showed tIt should be noted that the series of intracycle velocity variations of the divers’ bodies in flutter and breaststroke kicking were shifted in phases from the series of velocity variations of the tank . IdenticThe results of a comparison of underwater fin swimming performance using dolphin, flutter and breaststroke kicks both with and without diving gear were interpreted in terms of average swimming velocity, employing the parameters of spatiotemporal structure of the stroke and with reflection to the swimming economy. Intentional controlling of the strategy of propulsion generation in order to achieve optimal performance—oriented on a particular goal of divers was also taken into consideration.The dolphin kick swimming was the fastest in both trials, . This fiIndex) when swimming with or without diving gear  while flutter kicking in both trials  propulsion utilization has been verified, although this relationship was seen more clearly in swimming without diving equipment.The lowest variations in intracycle velocity  has been used as a measure of technical skill in all swimming strokes performed in both long and short distances . Zaton ew extent . Even leIndex). The flutter kick was not as fast as dolphin kick, probably owing to the increasingly high frequency of leg movements (SR), which directly led to a shortening of the SL. Consequently, in breaststroke kicking, the strategy of low SR when lengthening the SL led to a reduction in the economy of propulsion generation (SI) as well as to the relatively large variations in intracycle velocity, limiting the economization of its utilization (VIVIndex). Finally, it can be assumed that an optimal strategy for controlling performance in various fin swimming techniques without diving gear comprises lengthening of the SL while keeping the SR at the highest level possible in dolphin and flutter kicking, yet increasing the SR while keeping the SL at the longest level possible in breaststroke kicking.A number of studies ,21,23,28Index) through reducing the SR in dolphin kicking, lengthening the SL in flutter kicking and adjusting the SR to keep the SL at the longest level possible in breaststroke kicking. It seems that divers in these trials were unable to control the relationships between SR and SL as precisely as when swimming without diving gear. Therefore, they probably did not meet all necessary conditions to obtain the relatively high performance.In underwater swimming with diving gear, a complete layout of the dependencies between the examined parameters was not found . Therefoav) across the three leg-kicking techniques proved similar despite different relationships between the examined parameters (Sanders  has statrameters . Indeed,rameters  significIn search of the causes of inferior performance in underwater swimming with equipment , Fig 4, s in order to reach specific goals.Finally, turning back to consideration of performance in various fin swimming techniques through the prism of praxeology, the thesis can be formulated, that underwater fin swimming performance could be increased through implementation of different kicking techniques as the action-oriented skillA small sample size may constitute a potential limitation of this study, however the number of military divers at the highest level of proficiency is a priori limited. Additionally, the nature of their military commitments implies another limitation. Regarding the breaststroke kick preformed while swimming with fins, we would like to point out a high negative impact of this movement structure on the knee function. The swimmers and scuba divers should be aware of possible injuries that might result from external rotation in the knee and hip joints, while applying this technique.The motor pattern of dolphin kick seems to be the best solution for diving practitioners to enhance in fin swimming performance when obtaining a high velocity is the goal of their activity in both swimming with and without diving gear.A priori negation of breaststroke kick as a source of propulsion during underwater fin swimming seems to be unjustified, especially when one swims with diving gear. These motor patterns, as is the case of the flutter kick, could be successfully employed to enhance the fin swimming performance when the water activities are more focused on obtaining the utilitarian goals than on fastest swimming.Given the various goals of underwater swimming, the premises for an optimal strategy of controlling performance should be focused on decreasing the velocity variation, irrespective of the various leg-kicking techniques available. In fin swimming without diving gear, these strategies include the following: lengthening the SL while keeping the SR at the highest level possible in dolphin and flutter kicking and increasing the SR while keeping the SL at the longest level possible in breaststroke kicking. Controlling the relationship between the SR and the SL when swimming underwater with fins and diving equipment may not be as precise as when swimming without them due to the large cross-sectional area of the unstreamlined body as well as large inertial forces induced by the displacement of the air tank relative to the swimmer’s body. Therefore, this strategy could be implemented by decreasing the stroke rate in dolphin kicking, increasing the stroke length in flutter kicking and adjusting the stroke rate in order to keep the stroke length at the longest level possible in breaststroke kicking.


This dataset provides the perceptions of ordinary people on the relationship between societal acceptance of bribery, anti-bribery measures, socio-economic impacts of bribery, demographic factors and persistence of bribery practices. A multi-stage sampling technique was used to target the respondents. A total of 887 grassroots respondents participated, out of which 836 responses were used for quantitative data analyses. Statistical Packages for Social Sciences (SPSS) version 23 and SmartPLS3.0 were used to determine the reliability and validity of the data. The data is useful to the authorities in formulating strategies to deal decisively with the issues of bribery practices in Nigeria. The data is useful, as there exists a paucity of research on the perception of grassroots on bribery practices in Nigeria; the focus has always been on the perceptions of high profile individuals such as top business executives, lawyers, and international institutions among others.•The dataset is also useful to the international and non-governmental organizations such as the United Nations (UN), World Bank, International Monetary Fund (IMF), Transparency International (TI), International Police (INTERPOL), Human Rights Watch, among others in their further researches on the impact of bribery practices especially in Nigeria and the world at large.•The data are also valuable to local, state and federal government in Nigeria in dealing decisively with the issues of bribery practices as perceived by the grassroots. This is because the data provided an in-depth insight into the extent of societal acceptance and impacts of bribery practices in Nigeria.1A survey questionnaire technique was employed to acquire the dataset. A 5 points Likert scale rating that range from ‘strongly disagree’ to ‘strongly agree’ was used in conducting the survey. The questionnaire consisted of five sections. Section A was designed to collect data on the demographics of the respondents: gender, age, marital status, family size, educational status, job status and annual income. Section B contains instruments meant to measure the dependent variable (perceptions on the persistence of bribery practices in Nigeria). Section C deals with instruments that measured respondents’ perception of societal acceptance of bribery in Nigeria. Section D comprises of instruments used to measure the respondents’ views on the impacts of anti-bribery measures in Nigeria. Finally, section E contains instruments employed to measures the respondents’ opinions on the socio-economic impacts of bribery practices in Nigeria. The questionnaire is provided as a supplementary material in this article. The individual response to the questionnaire are reported in the Mendeley dataset.The first construct is the demographic factors of the respondents that represent the influence of the factors towards perceiving persistence of bribery practices in Nigeria where five items gender, marital status, family size, educational qualification and job status were included. The second construct is the persistence of bribery practices (dependent variable) that represents the respondents perception about widespread, continuity and permanency of bribery practices among others where ten items PBR_1 –PBR_10 were coded.The third construct is societal acceptance of bribery practices that assesses the respondents’ opinion of justification, tolerance and openness of bribery practices in Nigeria where nine items SAC_1 – SAC_9 were coded. Anti-bribery measures is the fourth construct that assesses perception of the respondents towards the impacts of policies, institutions and programs put in place to reduce bribery practices in Nigeria where twelve items ABM_1-ABM_12 were coded.Socio-economic impacts of persistence of bribery practices is the fifth construct that measures the socio-economic damages of persistence of bribery practices based on the perception of the respondents where fourteen items IMP_1-IMP_14 were coded. All the items are shown in In terms of marital status, The educational status of the respondents was also shown in Statistically, The issue of multicollinearity in the data was measured using tolerance (TV) and variance inflation factor (VIF) in SPSS version 23. The result is presented in The reliability and validity of the questionnaire items in respect of their corresponding constructs were thoroughly investigated using partial least squares-structural equation modeling (PLS-SEM) as recommended 2The data were acquired using a multiple stage sampling technique. The sampling was carried out in four phases (stages) and it involves clusters and simple random sampling methods. The first phase of the sampling involves dividing Abuja into six districts (clusters) namely; Abaji, Central Business, Bwari, Gwagwalada, Kuje and Kwali districts.At the second stage, two districts were selected by simple random sampling from the six districts  Through these process Central Business and Bwari Districts were selected.At the third stage, for each of the two districts selected at the second stage , three (3) area councils were selected also by a simple random sampling method as described above. In the Central Business district, Garki, Maitama and Wuse areas were selected. In Bwari District, Dutsen Alhaji, Kubwa and Katampe areas were selected. The six areas selected became the sampling frame.The fourth stage involves self-administering of 1000 questionnaires by the researcher and six research assistants. The target participants were identified by the researchers using heads of human resource departments in public and private institutions, whereas officials of associations of self-employed individuals were used to identify self-employed respondents. An introductory letter issued by the researcher's institution was provided to officials of the targeted participants as evidence for data collection purposes.The participants that were identified by the officials were randomly selected and handed the questionnaire. The participants were given two days to complete the questionnaire. In Garki, Maitama, Dutsen Alhaji, Kubwa and Katampe 140 questionnaires each were administered respectively while 160 were administered in Wuse to the grassroots.The data collected from the respondents totaling 887 were screened for missing values and outliers in SPSS version 23, 836 responses were found to be useful for data analyses. The SmartPLS3.0 was used to analyze the useful data.The authors have obtained informed consent from the participants after assurances were given to the participants that no one will be identified in this data collection exercise .Abubakar Saddiq Sani: Definition, Conceptualization, Investigation, Writing-original draft, Investigation, Formal analysis and Visualization. Abu sufian Abu bakar: Methodology, Software, Validation, Writing-Review and Editing and SupervisionThe authors hereby declared that they have no known competing interest financial or personal that could have influenced the outcome of this article.


In this report, we aim to present our algorithm and results of patients with congenital cardiac disorders who underwent surgical or interventional procedures during the peak phase of the pandemics in our country.The first COVID-19 case was diagnosed in Turkey on 11 March, 2020, and the peak phase seemed to end by the end of April. All the patients whom were referred, treated, or previously operated but still at the hospital during the peak phase of COVID-19 pandemics in the country were included into this retrospective study. Patient’s diagnosis, interventions, adverse events, and early post-procedural courses were studied.Thirty-one patients with various diagnoses of congenital cardiovascular disorders were retrospectively reviewed. Ages of the patients ranged between 2 days and 16 years. Seventeen cases were males and 14 cases were females. Elective cases were postponed. Priority was given to interventional procedures, and five cases were treated percutaneously. Palliative procedures were preferred in patients whom presumably would require long hospital stay. Corrective procedures were not hesitated in prioritised stable patients. Mortality occurred in one patient. Eight patients out of 151 ICU admissions were diagnosed with COVID-19, and they were transferred to COVID-19 ICU immediately. Three nurses whom also took care of the paediatric cases became infected with SARS-CoV-2; however, the children did not catch the disease.Mandatory and emergent congenital cardiac percutaneous and surgical procedures may be performed with similar postoperative risks as there are no pandemics with meticulous care and preventive measures. It is accepted as an escalating pandemic by World Health Organization2 it is a necessity to postpone elective cardiovascular procedures to the end of the pandemics in order to minimise the risk of transmission of the disease to an operated patient which may end up with the death of the case. It is also important to provide additional ICUs and ward beds for the patients infected with SARS-CoV-19 who require hospitalisation.As it is advised by worldwide national and international cardiology and cardiovascular surgery societies including our national society for cardiovascular surgery,3 Some of the cases are elective, whereas some require emergent procedures. Some has to be operated with robust timing; otherwise, they may lose the chance of ideal anatomical corrective option  or second-stage interventions . In addition, it is also possible to perform less invasive palliative and protective operations and postpone the main surgical treatment to a more appropriate stage to decrease the risk of the case . Moreover, with the increasing advances in technology and percutaneous techniques, many patients with congenital cardiac lesions also benefit from catheter-based treatment modalities.Patients with congenital cardiac defects account for a specific subgroup among patients with cardiovascular diseases, and indications for surgical and/or percutaneous interventions are diverse and versatile.There are no literature data regarding the results of congenital cardiac surgical or percutaneous interventions during the COVID-19 pandemics. In this report, we aim to present our institutional experiences with congenital cardiac patients during the COVID-19 pandemics.4 Since then tremendous switch in the healthcare system and social security services was pronounced. Our hospital was announced among the healthcare providers during the pandemics as a “pandemics hospital,” and various alterations were executed for the care of the patients with COVID-19 disease. Although a separate building was provided for the care of these patients, unfortunately, it became rapidly full and the main building, including the floor of the cardiovascular surgery ward, as well as other wards were started to be occupied with SARS-CoV-19-infected patients.The Ministry of Health officially declared the diagnosis of first COVID-19 case in Turkey by 11 March, 2020.The isolated ICU of the cardiovascular surgery branch with 18 beds with 4 isolated rooms spared for transplant cases became a general ICU. The other two high-volume ICUs of the hospital were reserved for the patients with the confirmed diagnosis of COVID-19, and the non-infected patients requiring intensive care were moved to cardiovascular surgery ICU. Unless confirmed with COVID-19, all the patients requiring intensive care and postoperative patients requiring ICU follow-up were allocated at the cardiovascular surgery ICU. If they are diagnosed with COVID-19 by nasopharyngeal swab, Polymerase Chain Reaction (PCR), or computerised tomography, they are transferred to one of the COVID-19 ICUs. The patients whom underwent cardiovascular surgery procedures were also followed at this ICU. Care was provided to all patients from different branches by the experienced constant staff of the cardiovascular surgery reanimation and nurse teams. Discharge from the ICU was adjusted between the reanimators and related branch physicians.The children with congenital cardiac disorders whom required ICU follow-up following percutaneous or surgical interventions were also allocated in this originally cardiovascular surgery, however, former general ICU. Paediatric cardiac patients were either transferred to the new born ICU when they are extubated and completely weaned off inotropes or discharged from the hospital directly from this unit with seldom ward follow-up.The patients whom were referred from other centres or admitted to our institution with the diagnosis or suspicion of congenital cardiac disorders during the peak period of the COVID-19 pandemics in the country or whom were previously operated; however, required hospitalisation after the first diagnosed case in the country on 11 March, 2020 was also included into this retrospective research. They were thoroughly investigated and evaluated by the paediatric cardiologists, paediatric cardiac surgeons, and anaesthesiologists and then the strategies were determined. All the patients coming from home without any infectious symptoms were either directly operated or percutaneously intervened. The cases with a history of hospitalisation longer than 24 hours were admitted to the isolation section of the ICU or refused if there were no available beds as a policy of the hospital. Patients were tested against COVID-19 and interventions were planned, unless emergent. The age, gender, body weight, diagnosis, history of previous interventions, the current procedures, duration of interventions, inotrope requirement, duration of mechanical ventilation, ICU and hospital stays, and adverse events were obtained from the institutional files. As a policy, all the studies regarding COVID-19 pandemics required special permission from Republic of Turkey, Ministry of Health. The study was approved by the Republic of Turkey, Ministry of Health. Further ethical approval was not obtained from the institutional ethics committee due to the retrospective nature of the research; however, the directors of the hospital were informed about the study.There were 31 patients whom were referred or admitted to our institution with the diagnosis of congenital cardiac defects between 10 March and 30 April, 2020. As a consensus of the hospital, all the elective and stable cases were postponed by 15 March, 2020. Among the postponed cases, there was a female patient aged 8 months with the diagnosis of tetralogy of Fallot with normal growth, oxygen saturation above 90%, and without hypoxic spells. There were two girls at the age of 40 months and 44 months with the diagnosis of large ostium secundum-type atrial septal defect and superior-type secundum atrial septal defect with partial pulmonary venous return anomaly, respectively, with stable conditions and they were advised to re-admit for surgical treatment following COVID-19 pandemics, unless an emergency situation occurs. There was a single ventricle case in stable conditions and with oxygen saturation around 88% whom actually require bidirectional Gleen and his procedure was postponed. There was another boy aged 4 months with the diagnosis of perimembraneous ventricular septal defect sized 7 mm in the maximum diameter with normal growth and without any anticongestive therapy and without frequent pulmonary infections; and surgical treatment was also postponed for this particular case.We were not able to accept a 10-day-old patient with the diagnosis of coarctation of aorta with depressed myocardial functions (ejection fraction: 40%–45%) whom was referred from another hospital, due to unavailability of isolation bed at our unit. We were informed that this baby was accepted by another hospital in the city for surgical treatment. The features of the patient whom were consulted but not treated at our institution are presented in Table In total, there were 25 patients whom received either surgical treatment or interventional procedure or both at our institution during the pandemics period in the country until the end of April. The demographic, interventional, operative, and postoperative features of the patients are summarised in Table Two patients were referred from another well-known institution. They had been operated, however, were on mechanical ventilator for 40 and 140 days, respectively. They received only supportive care at the cardiovascular surgery ICU of the institution; however, together with the COVID-19 adaptations of that university hospital, the paediatric cardiac cases were transferred to the paediatric ICU. Their primary physician was changed. Together with the change of their primary physician, better care and additional diagnostic measures to clarify the reason of not being able to be weaned off the ventilators were seeked. The patients were consulted with us. The diagnosis of the first case was intact ventricular septum with pulmonary atresia whom underwent left modified Blalock-Taussig shunt through left thoracotomy at the neonatal period followed by another modified Blalock-Taussig shunt between the brachiocephalic trunk and the main pulmonary artery (operation timing could not be identified). His last operation was a bidirectional Glenn procedure in February 2020. Investigations revealed increased Glenn pressure and occlusion of the left pulmonary artery. We attempted to percutaneously open the left pulmonary artery, however, could not be successful. The patient underwent surgical off pump left pulmonary artery thromboendarterectomy, left pulmonary artery reconstruction with a pericardial patch reaching till the left pulmonary hilus, a shunt from the brachiocephalic trunk to the left pulmonary artery, and right pulmonary artery banding. The surgical exploration of the mediastinum and the left pulmonary artery revealed extensive use of absorbable haemostatic materials over the pulmonary arteries, and lesser curvature of the aortic arch , undivided and not explored left modified Blalock-Taussig which was thought to be one of the facilitating reasons of left pulmonary occlusion due to intimal hyperplasia inside the graft and at the anastomosis line. The other patient had undergone arterial switch and ventricular septal defect closure procedures at the age of 10 days which was followed by right ventricular outflow tract reconstruction 44 days after the Jatene procedure. He was tracheostomised and on ventilator. Echocardiography at our institution revealed a 7 mm diameter inlet muscular ventricular septal defect with additional at least two 2–3 mm in diameter apical ventricular septal defects. The largest of the ventricular septal defect was closed percutaneously with a device. Both patients were transferred to the referring university hospital’s paediatric ICU. They are still followed at the paediatric ICU, require supportive ventilation therapy, receive antibiotherapy, and planned to be discharged as soon as optimal conditions are achieved.There were three patients with transposition of great arteries. Two of the patients had very small inlet-type ventricular septal defects. Two of the patients underwent balloon atrial septostomy preoperatively. All the patients were operated on the first 10 days of their lives. Arterial switch operations together with ventricular and atrial septal defects closures were performed in all patients. The postoperative courses were uneventful. Patients could be extubated in 72 hours and were transferred to the new born ICU free of inotropic support and without the need for inotropes. These patients were discharged from the hospital 25, 10, and 9 days after surgery. All the patients required change in the antibiotherapy from cefazolin to piperacillin and tazobactam combination.Three patients aged less around 1 month with the diagnosis of unbalanced atrioventricular septal defect, double inlet-double outlet single ventricle, and large perimembraneous (2 cm) and apical (1 cm) ventricular septal defects, respectively, underwent pulmonary banding operations with ductus ligation through left anterior thoracotomy. The patients weaned off the ventilator in 48 hours and were transferred to the new born ICU in good conditions. Two of the patients required antibiotherapy change to piperacillin and tazobactam combination. Another patient aged 83 days with the diagnosis of complete atrioventricular septal defect was at the hospital since birth. She had annulary pancreas and had abdominal surgery. She experienced sepsis attacks and alimentation problems. She received intravenous antibiotic and antifungal treatments and was in a critical condition. We performed patent ductus arteriosus ligation and pulmonary artery banding through left anterior thoracotomy in this case. Unfortunately, unexplained sudden death occurred in this patient on the 6th postoperative day.One patient aged 16 days with the diagnosis of aortic coarctation underwent coarctation repair (extended resection and end-to-end anastomosis). The other patient was an 86-day-old male with the diagnosis of aortic coarctation and small atrial and ventricular septal defects with a history of aortic balloon angioplasty. He underwent aorta patchplasty, weaned off the ventilator in 6 hours, and transferred to the ward in 2 days. However, the ventilation time was 96 hours due to increased secretions for the first case and transferred to the new born ICU 5 days after the operation. We had to change the antibiotherapy of the case to ceftriaxone and to piperacillin and tazobactam combination.A 6-month-old baby with large perimembraneous ventricular septal defect and systemic pulmonary hypertension with Down syndrome, growth retardation, and congestive heart failure despite anti-congestive therapy underwent ventricular septal defect closure. Ventilation time of the child was 24 hours, followed by 48 hours ICU stay, and 5 days hospitalisation.A 60-month-old girl with congenital atrioventricular block whom received pacemaker implantation through left thoracotomy in whom the battery had been implanted over the left diaphragm at the neonatal period underwent battery exchange. The battery was removed from the left hemithorax and the new battery was implanted under the rectus fascia on the left abdominal wall. The patient was from another town, kept in the hospital and could be discharged from the hospital 5 days after as soon as a special permit for intercity transfer was received.A 10-day-old girl with the diagnosis of supracardiac-type total anomalous pulmonary venous return underwent a corrective procedure. The sternum was left open for 48 hours and 2 days after sternal closure the patient could be extubated. She is still at the ICU at present in good condition. We needed to convert her antibiotherapy to meropenem and then added vancomycin.2 values.A boy aged 3 years with single ventricle physiology whom had undergone a modified Blalock-Taussig shunt operation at the neonatal period followed by a bidirectional Glenn and stent implantation to the right pulmonary artery presented to the clinic with 57% oxygen saturation. The catheterisation indicated stenosed right pulmonary stent and extensive arteriovenous fistulae in the right lung. The heart team decision was right pulmonary reconstruction and right pulmonary shunt and the patient underwent removal of the pulmonary stent, pulmonary reconstruction with a pericardial patch, and central shunt from the ascending aorta to the right pulmonary artery. By 1st of May, the patient is still on mechanical ventilator, with oxygen saturation ranging between 60% and 70% despite 80%–90% FiOAt the very early periods of the disease in the country, there were relatively five elective patients. The first case had undetermined double inlet and outlet ventricle with pulmonary atresia whom underwent right modified Blalock-Taussig shunt followed by bidrectional Glenn procedure previously and underwent fenestrated Fontan procedure. Total correction  was performed for the patient with tetralogy of Fallot. Another case was referred with the diagnosis of double aortic arch with feeding difficulties and dyspnoea and the patient underwent division of the non-dominant arch. The last case had large apical and perimembraneous ventricular septal defects with a history of pulmonary banding and the band occluding the right pulmonary artery underwent closure of the ventricular septal defects and pulmonary artery reconstruction. The last elective patient was a 16-year-old girl with Marfan syndrome with the diagnosis of anuloaortic ectasia whom was operated before the diagnosis of first COVID-19 case in the country, on 10 March, 2020. She underwent Benthall-deBono procedure. Either the ICU or the hospital stays of these patients exceeded the first diagnosis of COVID-19-positive patient in the country; thus, these patients were also added to the cohort. The single ventricle case was extubated in 6 hours. ICU stay was 2 days; however, the ward stay was complicated with alimentation and drainage complications and the patient could be discharged home after 13 days. The ventilation time and ICU stay for the patient with tetralogy of Fallot were 24 hours and 48 hours, respectively, and he was discharged home after 7 days. The patient with double aortic arch stayed 1 day at the ICU and discharged from the hospital in 4 days. The postoperative course of the patient with ventricular septal defects was complicated with rhythm problems, convulsions, and pulmonary infections leading to multiple intubations and extubation attempts and ICU stay lasted 18 days, but the patient could be discharged home on the postoperative 26th day. The Marfan syndrome patient stayed 1 night at the ICU and discharged home after 7 days.Except the balloon atrial septostomy performed for the cases with transposition of great arteries, one postoperative case who received percutaneous ventricular septal closure and another patient with unsuccessful pulmonary dilatation, there were seven other patients whom underwent catheterisation procedures. Five patients underwent diagnostic or percutaneous interventional procedures. A 2-day-old baby with ventricular septal defect and pulmonary atresia received diagnostic catheterisation which revealed sufficient pulmonary circulation through major aortopulmonary collaterals and oxygen saturation above 85%. The decision for the particular case was followed up at least during the COVID-19 pandemics and the patient was discharged home. Two patients with pulmonary stenosis  received successful balloon pulmonary valvuloplasty. A 14-month-old girl with the diagnosis of outlet muscular ventricular septal defect with growth retardation, dilated left heart chambers, and aortic insufficiency received transcatheter defect closure. A 156-month-old boy with previous stent implantation for the relief of aortic coarctation presented with uncontrolled hypertension and frequent headache attacks underwent percutaneous balloon dilatation of the stent. The isolated pulmonary stenosis case is still at the hospital due to bronchopulmonary dysplasia. The other pulmonary balloon case could be discharged from the ICU 3 days after the intervention. The remaining cases were discharged home the next day after catheterisation.Since the patients were followed at the general ICU, the beds of the patients were next to the beds of the patients of general ICU. The same nurse had to take care of the adult patients and paediatric cases at the same time. Between the first diagnosis of the COVID-19 disease in Turkey and till the end of April 2020, there were 151 patients admitted to our ICU. Eight patients whom were formerly negative for COVID-19 were later on diagnosed with the disease and were immediately transferred to the COVID-19 ICU of the hospital. One head nurse and two other staff nurses were diagnosed with COVID-19 during the 2-month period and were sent home for medical treatment and 14 days quarantine. Two nurses returned back to work with confirmed negative tests after quarantine. All the nurses also took care of the children until their COVID-19 diagnosis. The patients whom received care by these staff were tested against COVID-19 as soon as their nurses were diagnosed COVID-19 positive; however, serial tests ended up with negative results in these children.1 It is probably the second pandemics after the H1N1 flu in 20095; however, the most serious pandemics of the new century so far.COVID-19 has become a serious health problem rapidly after its initial diagnosis in December 2019 in Wuhan, China. The disease is caused by SARS-CoV-2, a virus that belongs to corona virus family. It is highly contagious and has been obvious that by the end of April 2020, COVID-19 is evident all around the world infecting people in all nations. The World Health Organization has announced COVID-19 as pandemics by 11 March, 2020.Unfortunately, the disease has not been taken into account very seriously despite warnings as a result of the lessons learned from increased mortality, morbidity, and hospitalisation rates from the initial experiences by many populations which ended up with a disaster with as high as 1000s of deaths every day and very sadly even inability to hospitalise many patients. Moreover, the economical power and development status of many countries have been insufficient to overcome the need for medical care of the patients despite converting many closed facilities including schools, dormitories, stadiums, or even the high-velocity trains into “mobile hospitals”.6 is able to estimate accurately the extent to which COVID-19 will affect the population in terms of rates of incidence, duration, and recovery.7 On the other hand, the healthcare politics and strategies against the dissemination of COVID-19 or treatment of patients with COVID-19 seems to be successful so far with the decreasing number of cases by the end of April 2020 as well speculations through certain graphics indicating a possible end of the disease soon in our country. The novel corona virus has infected more than 200,000 people all around the world, affecting daily lives and changing the world into an economical burden.8 The pandemic also has changed the daily routine of doctors including cardiovascular surgeons through different ways.As the number of cases starts to increase across our country, public health authorities strongly advised social distancing, self-isolation, and self-quarantine which were supported by the medical societies as well as social media. The government also announced certain precautions including curfew of elderly (above 60 years of age) and youngsters (below 20 years of age) at first. It was followed by national curfew staring at the weekends and followed by curfew at the weekends as well as certain other days to constrain COVID-19 and limit its transmission. However, nobody as in other countries9 ranging between increased incidence of venous thrombosis11 and myocarditis leading to decreased ejection fraction.12 In addition, the course of the disease is also more severe in patients with existing cardiovascular disorders. It may even be worse in a postoperative cardiac case, as the postoperative period is an inflammatory state and if the patient is infected with corona virus, the course of the pulmonic viral infection may be drammatic.7Certain issues have to be addressed regarding the cardiovascular disorders during the course of the pandemics and COVID-19 disease. Although COVID-19 is primarily a disease of the lungs, lessons learnt through its course indicated at least 15% patients face with cardiovascular comorbidities7 Obviously, everything is spared for the care of COVID-19-positive cases requiring hospitalisation. An additional issue rose with the risk of infection of the healthcare providers and non-COVID-19 patients requiring hospitalisation. Eventually, many doctors, nurses, and other healthcare personnel got infected, many of them catching the disease most probably at the hospitals. Hence, it has been logic and ethical to postpone elective procedures which have to be decided by a team. Mavioglu et al13 developed a level of priority statement for adult cardiovascular procedures and concluded that cases should be considered on an individualised basis by a heart team. Because, not only the patients themselves are at risk of COVID-19 but also the family members would be at substantial risk.The pandemic very shortly ended up in extreme shortage of available ICUs and ward beds, ventilators and other medical equipment, medications, blood and blood products, and also shortage of healthcare providers all around the world.14 Congenital cardiac surgery and cardiology are two dedication branches and have to be performed by highly skilled and well-educated physicians; otherwise, outcomes of the patients may be incomplete or disastrous. In addition to the capacity and capability of the physicians dealing with congenital cardiac disorders, they need to be backed up appropriately to save the lives of the children with congenital cardiac pathologies. Because of the current challenging pandemic status of the healthcare facilities, congenital cardiac procedures have to be adjusted wisely. Prioritisation, difficult decisions, and triage of patients have to be adjusted by highly specialised heart team composed of cardiac surgeons, cardiologists, and anaesthesiologists having experience with congenital cardiac pathologies. Luckily, unlike adults, the major problem has not been related to COVID-19 disease itself in the paediatric population; however, routine care of the children with CHDs has been compromised due to the restriction of the healthcare resources including available beds, ventilators, or healthcare providers solely for CHD patients. Even the paediatric cardiac surgeons are deployed for the care of the patients with COVID-19 temporarily.3Incidence of congenital cardiovascular disorders is approximately 1% and babies will continue to be born.It was the same situation at our institution. We postponed all the elective patients with congenital cardiac pathologies and operated on only emergency cases or patients otherwise would lose the chance of corrective or secondary procedures such as patients with transposition of great arteries or patients with single ventricle physiologies. We preferred palliative procedures in patients whom presumed to have a long ICU stay, e.g., pulmonary band for a critically ill baby with atrioventricular septal defect or a borderline right ventricular volume in a patient with large ventricular septal defects. Additionally, the tendency was percutaneous procedures such as dilatation of the previously implanted stents, ductal and right ventricular outflow tract balloons, or stents instead of shunt procedures or device closure of septal defects.3 If possible, online or phone conversations rather than face to face at the hospital setting should be preferred. It is important to minimise the exposure of patients from outside visitors including families in case of a pandemic situation. Every visitor has the risks of carrying infection to the hospital as well as getting infected at the hospital environment especially when considering asymptomatic shedding of the truly infected people by the SARS-CoV-2. Social distancing and wearing face masks are crucial for the prevention of the transmission of airborne viral diseases.3 Although psychologically it is not easy for the families having their children receiving congenital cardiac surgery, the ICU visits of the babies were prohibited at our institution and breast milk is accepted which is prepared at home. The ward stays were as short as possible and only one parent is allowed with the child. In order to minimise the risk of being infected by increased exposure or because of allocation for the care of the COVID-19 cases, the training activities of the residents are also postponed. The cardiac surgeons or paediatric cardiac surgery residents may also play a crucial role during the extracorporeal membrane oxygenation support of the hypoxic COVID-19 cases.3The timing of surgery in CHDs is determined depending on patient-related factors as well as guidelines. The responsibility of the patient in such a pandemic situation should be taken with a heart team, and the pros and cons of the decision should be discussed with the families in details and with transparency.3 Isolation beds may also be preferred until the results of the tests from outside hospital admissions. Additionally, the procedures or even the decisions regarding the procedures of the paediatric cases may be postponed until the results of the tests. Otherwise, in case of emergency settings and especially patients with a history of COVID-19 exposure or symptoms of airway tract infection, it may be wise to perform the procedures in operating theatres spared only for COVID-19-positive cases.Testing of children and hospital admitants against COVID-19 should have an important influence during decision making for the paediatric cardiac patients.All of our patients had to stay next to the adult patients from various specialties including general surgery, neurosurgery, orthopedics, etc. or patients requiring ICU follow-up in a COVID-19-negative ICU. We believe such kind of hospitalisation may have contributed to especially the additional antibiotherapy and lengthy hospital stays.There are three major limitations of the study. First of all, it is a retrospective research. The second limitation is the small size of the cohort. When taking into account all the factors such as the first patient diagnosed in the country and the peak period until the end of April, together with preventive and economic measures to spare healthcare supplies for COVID-19 cases as well as strategy to postpone elective cases, we ended up with 25 cases. Two of our cases were referred from another university hospital paediatric ICU, and as soon as the patients are stabilised after their interventions, they were transferred to the referring centre for ICU follow-up in order to provide bed for the other patients requiring intervention at our institution. The same was also applied for the patients coming from the neonatal ICU of our institution. Otherwise, probably we would not be able to reach that number of cases due to the shortage of the ICU beds. The last limitation is the short postoperative follow-up period of the patients to the maximum of less than 2 months. Still some of our patients are at the hospitals or ICUs. Despite three of the nurses at our ICU were diagnosed with COVID-19, two have returned back to work after their treatment and quarantine. The patients whom received care from these nurses did not catch the disease confirmed with serial SARS-CoV-2 PCR presumably due to meticulous preventive measures such as routine use of masks. The lengthy stay of the cases or change in the antibiotic regimes may be due to other reasons including patient-related factors as well as mixed hospitalisation with patients from other medical divisions and chronic ICU patients.14 Unlike many branches, cardiac evaluation and required interventional procedures have to continue to save the lives of many patients with congenital cardiac disorders. Literature lacks a level of priority statement for the patients with congenital cardiac disorders; however, the decisions have to be made with a multidisciplinary paediatric heart team approach. Despite many preventive measures, either we or the patients will inevitably somehow catch SARS-CoV-2. Despite limited resources and risk of infection, it is still possible to conduct congenital cardiac procedures with meticulous care and physician protective equipments to prevent disease transmission to the patients.Birth is inevitable, and the percentage of congenital cardiac defects has not changed for long as being 1%.


Given increasing interest in using the capability approach for health economic evaluations and a growing literature, this paper aims to synthesise current information about the characteristics of capability instruments and their application in health economic evaluations.A systematic literature review was conducted to assess studies that contained information on the development, psychometric properties and valuation of capability instruments, or their application in economic evaluations.The review identified 98 studies and 14 instruments for inclusion. There is some evidence on the psychometric properties of most instruments. Most papers found moderate-to-high correlation between health and capability measures, ranging between 0.41 and 0.64. ASCOT, ICECAP-A, -O and -SCM instruments have published valuation sets, most frequently developed using best–worst scaling. Thirteen instruments were originally developed in English and one in Portuguese; however, some translations to other languages are available. Ten economic evaluations using capability instruments were identified. The presentation of results show a lack of consensus regarding the most appropriate way to use capability instruments in economic evaluations with discussion about capability-adjusted life years (CALYs), years of capability equivalence and the trade-off between maximisation of capability versus sufficient capability.There has been increasing interest in applying the capability-based approach in health economic evaluations, but methodological and conceptual issues remain. There is still a need for direct comparison of the different capability instruments and for clear guidance on when and how they should be used in economic evaluations. Economic evaluations assess whether an intervention provides value for money through the comparative analysis of alternative courses of action in terms of both costs and consequences . The assThere has been increasing interest in developing instruments for using the capability approach in the measurement and valuation of outcomes for health economic evaluations. Capability instruments have been in the public domain for over a decade and publications have started to shift from methodological issues towards use of the measures within economic evaluations. Some decision-making institutions currently recommend the inclusion of capability measures in economic evaluations in certain contexts. The Zorginstituut in the Netherlands  recommenHowever, the choice between instruments and their practical application in particular contexts lack a systematic approach. For instance, the ICECAP-O recommended by NICE is targeted at a subgroup of the population (older adults), whilst the ASCOT was specifically developed for the assessment of social care interventions. A recent review of the literature examined current trends in the application of ICECAP-O . The autThe identification of papers was based on two main approaches: a traditional systematic literature search and a comprehensive pearl growing method . The greFirstly, we conducted a systematic literature search. Search terms combined expressions for economic evaluation and frequently used terms for the capability approach, including synonyms and names of instruments most well-known in the area of health economics. Search terms are presented in Appendix The term ‘capability’ produces very broad ranging results when used as a search term due to its wide range of meanings, including lay meanings. The so-called comprehensive pearl growing method  is a tecTwo waves of the pearl growing method were conducted: one focusing on the development of instruments and a second wave related to the application of the instruments. A third wave was deemed unnecessary because the identified last generation of seminal papers were published only recently and have not been cited yet. The results are presented in Table English or German languages. (2) Scope of study is the area of health or health-related interventions, including any interventions specifically targeting the promotion of health and prevention and treatment of ill-health irrespective of the sector where these were implemented. Hence, our study also included potentially relevant studies from the social care and public health sectors. (3) Focus of research is the evaluation or assessment of the outcomes of interventions using the capability approach. (4) Paper includes information on the use (or recommended use) of the capability approach in economic evaluations. (5) Paper is an applied evaluation OR focuses on the development, psychometric validation (or comparison to other tools) or preference valuation of instruments.Titles and abstracts were sifted by two researchers (TL and AL) and studies were included for further assessment if they met the following inclusion criteria: (1) Full paper available in The full paper was retrieved if a study met the inclusion criteria based on its title and abstract. Consequently, full papers were assessed by two researchers (TH and AL) for inclusion based on their contribution to at least one of the aims of this literature review and subsequently allocated to the categories of either (i) applied evaluations  or  methods papers. Methods papers were further categorised based on their relevance to the identification, measurement and valuation of outcomes, as well as the practical application of tools and theoretical contributions. Papers were grouped into categories of (ii) instrument development, (iii) psychometric validation or quantitative comparison of instruments, (iv) preference valuation of instruments and (v) methods for incorporation of the capability approach in economic evaluations. The latter one includes potential fields of application, approaches to use the results, incorporation of the results into a potential framework, for instance, Capability-Adjusted Life Years (CALYs), years of full capability or years of sufficient capability equivalence, etc. Some of the studies with significant theoretical contributions to the application of the capability approach in health economic evaluations which did not fit the above criteria were noted for discussion.No specific quality assessment was applied, all studies which provided information on either the psychometric properties or use of capabilities instruments in economic evaluations were included. The instruments were assessed based on their psychometric properties according to the COSMIN checklist , feasibiSeparate data extraction forms were created for empirical and psychometric evaluation (and other methods) studies. The search for information on valuation included any kind of preference-based valuation of instruments (or their dimensions/domains) and the existence of value sets. Further information on data extraction is presented in Appendix Trends in the literature were analysed based on the number of different types of studies published each year. The information elicited from the studies was structured according to the capability instrument in question. Information about economic evaluations, and the psychometric properties and correlation coefficients from studies comparing instruments are presented in review tables. Due to the variability of methods used in the validation and comparison studies, only narrative synthesis, including tabulation and frequency analyses, was conducted as no statistical pooling was possible. The information gathered was synthesised in a qualitative rather than quantitative manner by TH.The literature search identified 98 studies for inclusion  were found between capability instruments: ASCOT/ICECAP-O  and ICECn = 23) of the included validation and comparison studies as a HRQoL measure. In most cases, the 5L version of the EQ-5D instruments provided higher correlation coefficients compared to the 3L version. The higher correlation with capability instruments could be explained by lower ceiling effects and higher sensitivity to minor changes in the 5L version compared to the 3L version.The examined studies provided very diverse estimates for the correlations between Health-related Quality of Life (HRQoL) and the different capability instruments. Most studies compared the ASCOT, ICECAP-A and ICECAP-O instruments with either disease-specific or generic HRQoL instruments. A wide range of disease-specific instruments were applied across studies, mainly being used when informants consisted of patients and social care recipients. EQ-5D-3L/-5L was used in 92%  of Dutch, community-dwelling frail older adults. Simon et al. [In terms of ease of understanding, Bailey et al.  investign et al.  exploredn et al. .The sensitivity of the capability instruments to measure changes is generally reported to be higher than in case of HRQoL measures , 31–34. From the reviewed 14 capability instruments, only four have a published valuation set. These used the best–worst scaling method, most often relying on the MaxDiff model. Informants mainly came from the general public. There is no published evidence available for the valuation of the remaining ten capability questionnaires Table .Table 6VTen applied evaluations were identified in this review that have used a capability-based instrument as secondary outcome measure in health economic evaluations. No economic evaluation was found where a capability instrument was used as a primary measure of health outcomes. The information extracted from the applied evaluations is presented in Table The number of economic evaluations reporting the use of a capability instrument has increased in recent years and further increases can be expected given that this search identified a number of recent study protocols  physical activity and diet; (2) patient empowerment; (3) multidimensional poverty and (4) assessments of health and social care interventions. The authors also noted that there is a noticeable non-reliance on health status as a sole indicator of capability in health, and differences were found across studies in approaches to applying mixed methods, selecting capability dimensions and weighting capabilities. The current review identified applied economic evaluations from areas with widely accepted issues related to outcomes beyond the QALYs framework, e.g. mental health, visual impairment, chronic diseases and health decline in older people.A recent review  focused in high-income countries. Second, questions of the relevant instruments should capture voluntary and involuntary positions because an applied conceptualization of the capability approach includes opportunity as well as achievement. Third, methods for weighting capability and threshold values should be established, similar to QALYs. Finally, a trade-off should be made between the maximisation of capability and equity.The presentation of results in the included economic evaluations demonstrate that there is a lack of consensus regarding the most appropriate way to use capability instruments in economic evaluations. Some authors present cost and outcome data separately and conduct a cost-consequence analysis –45, whilMitchell et al.  proposedrepresent only one combination and ignore the value of choice in the capability set, or represent one combination that is not actually achievable by the individual. In addition, existing methods of valuing capability may be inadequate because they do not consider that capability is a set. (Although the Oxford instruments were developed based on Nussbaum’s 10 basic human capabilities.) Hence, it may be practically more feasible to measure and value capability approximately rather than directly. Nevertheless, the argument is based on the questionable assumption that all capabilities have to be traded against other capabilities.The current state of the art identified in the reported economic evaluations applying the capability approach to their assessment are in line with the previously identified main challenges , includiThis systematic literature review about capability instruments in economic evaluations of health-related interventions included 98 articles and identified 14 capability-based instruments. It provides a unique, comprehensive synthesis of the relevant evidence by focusing on the full spectrum of potentially available capability measures and summarising the practical and theoretical aspects of use of these instruments in economic evaluations. Most identified information related to the ASCOT, ICECAP-A, ICECAP-O and OxCAP-MH instruments.The development of capability instruments relies on methods similar to those applied in the case of HRQoL measures. Capability instruments were often compared to EQ-5D, but less often to each other. Possible reasons for this are that some instruments are population or disease-specific, and that the inclusion of two instruments measuring the same concept in an applied evaluation study is assumed to unnecessarily increase participants’ completion burden. In general, the information identified in the literature regarding the comparison of capability measures with other instruments could not be used for a pooled analysis. This is mainly due to the vast variation in the correlation measures used, the instruments compared, the characteristics of the populations and the number of informants. Despite the diverse quantitative estimates for the correlations with EQ-5D, the different capability instruments and the limited available data, this review confirms that capability measures capture a wider range of outcomes than the EQ-5D and may be more responsive when an intervention is likely to have broad impacts on HRQoL. Following the guidelines  to evaluThree of the identified 14 capability instruments were used in applied economic evaluation of interventions in the health and social care field; however, only as secondary outcome measures. Eight of the identified ten applied economic evaluations were conducted in the United Kingdom. This may be the result of the fact that the measures were developed in the UK and only available in English for some years. From the perspective of  economists concerned with economic evaluations, a good outcome measure should possess three main characteristics . First, Major limitations of this study design include that the search was limited to English and German. Next, this review only assessed instruments and studies reported in the literature, and a thorough grey literature search could not be conducted due to difficulties with the search term capability. In terms of grey literature, only dedicated websites of capability instruments were reviewed for relevant information. This resulted in some limitations, for instance, some cost-effectiveness components of studies that have used ASCOT have not been written up as journal articles and fell therefore outside the findings of this review , 119. FuThere has been an increasing interest in the application of the capability-based approach in economic evaluations of health-related interventions. Different instruments are available and the choice between them should be based on both the research question and the characteristics of the instruments. Further research should focus on the comparison of the existing capability instruments and examining the correlation across capability measures. This would help future researchers in choosing the most suitable capability instrument for their study and provide further information for instrument developers.


Stem cell therapy provides new insights for the treatment of diseases or disorders that cannot yet be successfully managed through conventional care. Current cell-based approaches are mainly focused on the use of Mesenchymal Stem Cells (MSCs) which are multipotent stem cells with unique biological properties and are readily available from almost every organ and tissue. MSCs are becoming widely used to improve outcomes for multiple clinical scenarios: heart failure, wound healing, bone regeneration, and many others. Despite promising in vitro and in vivo results, the need for extensive manipulation steps to obtain sufficient cell numbers for delivery significantly increases the regulatory, practical, and financial barriers for the routine use of these novel therapies. Helping to overcome some of these limitations, the use of micrografts represents a suitable approach for tissue regeneration. Micrografting can be used to deliver not only progenitor cells but also growth factors and matrix extracellular components naturally available in the tissues which further increase the regenerative potential.Only few clinical trials have reported the efficacy of stem cell therapy; further research must be conducted to investigate also the safety of these techniques in the long term. Micrografting is attracting a growing interest from the research community since it involves easy/quick and simple procedures which reduce the amounts of donor tissues required while reducing morbidity.In this special issue, new procedures able to promote repair or regeneration in areas such as plastic surgery and wound healing are reported, using both stem cells and micrografts. In the manuscript by M. M. Bashir et al., the authors evaluate the effect of adipose tissue grafts mixed with adipose tissue-derived stem cells (ASCs) to promote fat graft retention in patients with contour deformities of the face showing an improvement in clinical outcomes when compared to the control group. The papers from M. Riccio et al. and M. M. Tresoldi et al. report the results from two clinical trials investigating the use of dermal micrografts in the treatment of traumatic or complex wounds in different patient populations. M. Riccio et al. present the management of 70 patients affected by traumatic wounds of the lower and upper limbs characterized by an extensive loss of substance. The results showed complete wound healing after 35 to 84 days. On the other hand, M. M. Tresoldi et al. treated elderly patients with wither micrografts or another dermal skin substitute, aiming to compare the efficacy for wound repair of both tissue replacement therapies. All patients reached a good degree of reepithelialization, but the authors failed to demonstrate a statistically significant difference between both groups. Finally, the study from A. Andreone et al. proposes a new approach for the management of burns based on the combination of platelet-rich fibrin and micrografts as a spray-on skin, reporting a rapid reepithelialization and impressive resurfacing.This special issue also introduces the reader to fine original basic research focused on the biological and cellular mechanisms involved in tissue repair in different conditions, helping to better elucidate some of the key players activated in these processes. The study conducted by C. Zhang et al. assessed the role of autophagy in cavernosal endothelial dysfunction of diabetic rats, explaining the therapeutic effect of urine-derived stem cells (USCs) which upregulated autophagic activity in the cavernosal endothelium, ameliorating cavernosal endothelial dysfunction and improving erectile dysfunction. Another interesting study carried out by F. Wang et al. explored the potential of injectable hydrogels as cell-carrying scaffolds able to mimic the condition of the natural extracellular matrix (ECM) of nucleus pulposus (NP), providing binding sites for cells. The authors reported that, in rats, the transplantation of injectable hydrogel-loaded NP-derived MSCs can delay the level of intervertebral disc (IVD) degeneration while promoting its regeneration and restoring the structure and ECM content of degenerated NP eight weeks after treatment.Skeletal muscle has a remarkable capacity to regenerate following injury due to the presence within the adult muscle of a tissue-resident stem cell population known as satellite cells (SC). These cells remain quiescent until physical exercise, or muscle damage induces their activation. In the manuscript by S. Aguanno et al., the researchers present a culture model of the myogenic C2C12 cell line in suspension, able to self-assemble in three-dimensional cultures and to form a system able to preserve the quiescence and the staminality of these cells. The findings from this study support the conclusion that this model could be used to investigate the pathways controlling SC quiescence entrance and maintenance.Micrograft therapies are a promising and affordable alternative to improve skin regeneration through enhancement of the endogenous wound repair processes. In the publication from M. Balli et al., the authors provide new insights which might contribute to a better understanding of the molecular pathways involved in micrograft-induced wound repair. Remarkably, the authors identified new key players in the wound healing process such as the active protein-1 (AP-1) and member Fos-related antigen-1 (Fra-1) which enhanced cell migration in mouse adult fibroblasts and human keratinocytes treated with soluble. These results were confirmed when inhibition of both ERK and AP-1 completely reverted the in vitro wound closure otherwise induced by the soluble micrograft treatment. This outcome highlights the important role of ERK-dependent transcriptional activity of AP-1 in the promotion of micrograft-induced wound closure.We sincerely hope that the articles published in this special issue can help researchers to better understand the potential roles of stem cell therapy and micrografting techniques for tissue regeneration, including the different advantages and disadvantages of both approaches. Further, the basic research manuscripts included in the issue provide new insights that improve the current understanding of the cellular and molecular mechanisms involved in the wound healing process, especially in pathological conditions such as diabetes or intervertebral disc degeneration.


Phototransduction reactions in the rhabdomeric photoreceptor are profoundly stochastic due to the small number of participating molecules and small reaction space. The resulting quantum bumps (QBs) vary in their timing (latency), amplitudes and durations, and these variabilities within each cell are not correlated. Using modeling and electrophysiological recordings, we investigated how the QB properties depend on the cascade speed and how they influence signal transfer. Parametric analysis in the model supported by experimental data revealed that faster cascades elicit larger and narrower QBs with faster onsets and smaller variabilities than slower cascades. Latency dispersion was stronger affected by modification of upstream than downstream activation parameters. The variability caused by downstream modifications closely matched the experimental variability. Frequency response modeling showed that corner frequency is a reciprocal function of the characteristic duration of the multiphoton response, which, in turn, is a non-linear function of QB duration and latency dispersion. All QB variabilities contributed noise but only latency dispersion slowed and spread multiphoton responses, lowering the corner frequency. Using the discovered QB correlations, we evaluated transduction noise for dissimilar species and two extreme adaptation states, and compared it to photon noise. The noise emitted by the cascade was non-additive and depended non-linearly on the interaction between the QB duration and the three QB variabilities. Increased QB duration strongly suppressed both noise and corner frequency. This trade-off might be acceptable for nocturnal but not diurnal species because corner frequency is the principal determinant of information capacity. To offset the increase in noise accompanying the QB narrowing during light adaptation and the response-expanding effect of latency dispersion, the cascade accelerates. This explains the widespread evolutionary tendency of diurnal fliers to have fast phototransduction, especially after light adaptation, which thus appears to be a common adaptation to contain stochasticity, improve SNR and expand the bandwidth. Phototransduction cascades in the rhabdomeric photoreceptors of invertebrates and the ciliary photoreceptors of vertebrates, while similar in their first stages, differ in their outcomes and regulation mechanisms. One salient difference is that in the photoreceptors of many insect species the delay of small responses decreases drastically after light adaptation. Here we performed an in-depth analysis of phototransduction in the insect microvillus and discovered hitherto unknown dependencies between the parameters of the cascade output, the quantum bump, and the cascade speed, supported by experimental data. Faster cascades produced faster, larger and narrower quantum bumps with smaller variabilities than slower cascades. We show that the differences in the cascade speed, either between species occupying dissimilar visual ecological niches, or between adaptation states, have profound consequences for photoreceptor signaling. Firstly, narrow and more synchronous bumps produced by fast cascades better transfer higher frequencies contained in visual signals, increasing the photoreceptor bandwidth. Secondly, a decrease in the level of noise due to the cascade acceleration compensates for the loss of signaling accuracy, which occurs when the signal duration decreases. We propose that acceleration of phototransduction is a powerful mechanism in both evolutionary and situational optimization of photoreceptor signaling. These two sources of noise, correspondingly the extrinsic photon and the intrinsic phototransduction (or transduction) noises, change with light intensity and photoreceptor adaptation state, and represent two main determinants of the overall noise in the graded voltage response. They limit information transfer by the photoreceptor and generally the reliability of motion detection in the visual system  interval for the lognormal and  interval for the normal distribution both contain approximately 2/3 of the probability. In our experiments, the standard deviations computed for the lognormally-distributed latencies differed little from the scatter values (the differences were in most instances within 10%). Because of the negligible differences between the two dispersion measures and for the sake of convenience, we used standard deviations in the various composite response reconstruction experiments presented.Both in simulations and experiments, QB latency distributions were best described by a probability density function of the lognormal distribution, although as mean latency decreased, the shape of the distribution approached the normal distribution. We fitted the latency distributions with lognormal equations and determined the medians and measures of scatter. The scatter interval can be defined as:In contrast, amplitude distributions obtained in simulations were characterized by variable skewness. For instance, as the cascade slowed the shape of the amplitude distribution evolved from a pronounced positive to negative skew. This did not allow using a lognormal distribution to describe the amplitude statistics. In the experiments, we observed both clearly lognormal and normal amplitude distributions. However, the former were caused by a loss of smaller amplitudes during QB detection since reliable separation of voltage bumps from the membrane noise of similar amplitude was usually impossible. Therefore, here we used mean values and standard deviations to describe the QB amplitude statistics. Likewise, the QB half-width and 25–75% rise slope distributions were generally normal and thus described using means and standard deviations.Spearman’s rank order correlation coefficient  was used in analyses of correlations. The data presented in figures can be found in the supporting S1 Data(XLSX)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S1 Text(DOCX)Click here for additional data file.