Evaluation of the Effect of Early-Onset Steroid Treatment in the COVID-19-Positive Pregnant Women on Pregnancy Outcomes.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acute respiratory distress and preterm delivery are the two major complications induced by SARS-CoV-2 infection during pregnancy. In the presence of dyspnea, the use of systemic corticosteroids was recommended in pregnant and non-pregnant groups. Our primary aim was to investigate the effect of early-onset steroid treatment on mortality and adverse effects in pregnant women with COVID-19. Our secondary aim was to investigate the effect of steroid treatment on the length of hospital stay and intensive care unit (ICU) stay, and duration of treatment. The study also investigated infection, preterm birth, and ideal body weight (lbw) in newborns. METHODS: In this retrospective study, 253 patients were divided into three groups according to steroid administration. In Group 1 patients (n:112), treatment was started at the time of hospitalization. In Group 2 patients (n:90), treatment was started at least 24 h after hospitalization. Group 3 consisted of patients (n:51) who did not receive steroid treatment. Methylprednisolone (32 mg/day) was given to pregnant patients with a gestational age below 24 weeks or above 34 weeks, and dexametazone (6 mg/day) was given in four doses followed by 32 mg/day methylprednisolone for the others (whose baby was at a gestational age of 24 weeks and above but less than 34 weeks). RESULT: The hospital stay, ICU stay, and steroid administration time were significantly lower in the Group 1 when compared to the others (p < 0.05). The steroid treatment requirement was 4.4 days in Group 1 and 5.7 days in Group 2 (p < 0.05). While no death was observed in Group 1, one patient died in Group 2 and three patients died in Group 3. There was no difference between the groups in terms of complications, including preterm labor. CONCLUSIONS: No death was also observed with early-onset treatment. Early-onset treatment may be beneficial for fewer hospitalizations, fewer ICU stays, and less mechanical ventilation requirement in pregnant women with COVID-19. In addition, with early treatment, the total number of steroid administration days was reduced, which is important in terms of reducing the risk of side effects.

A mathematical model of mobility-related infection and vaccination in an epidemiological case.

In this study, we established a system of differential equations with piecewise constant arguments to explain the impact of epidemiological transmission between different locations. Our main goal is to look into the need for vaccines as well as the necessity of the lockdown period. We proved that keeping social distance was necessary during the pandemic spread to stop transmissions between different locations and that re-vaccinations, including screening tests, were crucial to avoid reinfections. Using the Routh-Hurwitz Criterion, we examined the model's local stability and demonstrated that the system could experience Stationary and Neimark-Sacker bifurcations depending on certain circumstances.

Modeling a SEIVRS dynamic behavior with transportation-related transmissionEstablishing a system of two urban as differential equations with piecewise constant argumentsStability analysis of disease-free and co-existing equilibrium pointsAnalyzing bifurcation types around the disease-free and co-existing equilibrium points.Illustrating numerical scenarios that were applied during the pandemic event.

Diagnostic approach of tuberculous lymphadenitis in a multicenter study.

INTRODUCTION: Tuberculous lymphadenitis (TBLN) is the most common infectious etiology of peripheral lymphadenopathy in adults, in Turkiye. This study aimed to identify the demographic, clinical, and laboratory variables that differentiate TBLN from non-tuberculous lymphadenitis (NTBLN), as well as the etiology of lymphadenopathy in adults. METHODOLOGY: Patients who were over 18 years old and were referred to the infectious disease outpatient clinics with complaints of swollen peripheral lymph nodes, and who underwent lymph node biopsy between 1 January 2010 and 1 March 2021, were included in this multicenter, nested case-control study. RESULTS: A total of 812 patients at 17 tertiary teaching and research hospitals in Turkiye were included in the study. TBLN was the most frequent diagnosis (53.69%). The proportion of patients diagnosed with TBLN was higher among females; and among those who had a higher erythrocyte sedimentation rate, positive purified protein derivative test, and positive interferon-gamma release test result (p < 0.05). However, TBLN was less frequent among patients with generalized lymphadenopathy, bilateral lymphadenopathy, axillary lymphadenopathy, inguinal lymphadenopathy, hepatomegaly, splenomegaly, leukocytosis, and moderately increased C reactive protein levels (p < 0.05). CONCLUSIONS: Identifying the variables that predict TBLN or discriminate TBLN from NTBLN will help clinicians establish optimal clinical strategies for the diagnosis of adult lymphadenopathy.

A mathematical model of COVID-19 and the multi fears of the community during the epidemiological stage.

Within two years, the world has experienced a pandemic phenomenon that changed almost everything in the macro and micro-environment; the economy, the community's social life, education, and many other fields. Governments started to collaborate with health institutions and the WHO to control the pandemic spread, followed by many regulations such as wearing masks, maintaining social distance, and home office work. While the virus has a high transmission rate and shows many mutated forms, another discussion appeared in the community: the fear of getting infected and the side effects of the produced vaccines. The community started to face uncertain information spread through some networks keeping the discussions of side effects on-trend. However, this pollution spread confused the community more and activated multi fears related to the virus and the vaccines. This paper establishes a mathematical model of COVID-19, including the community's fear of getting infected and the possible side effects of the vaccines. These fears appeared from uncertain information spread through some social sources. Our primary target is to show the psychological effect on the community during the pandemic stage. The theoretical study contains the existence and uniqueness of the IVP and, after that, the local stability analysis of both equilibrium points, the disease-free and the positive equilibrium point. Finally, we show the global asymptotic stability holds under specific conditions using a suitable Lyapunov function. In the end, we conclude our theoretical findings with some simulations.

Evaluation of clinical and laboratory findings in severe group COVID-19 pregnants without comorbidity.

BACKGROUND: COVID - 19 disease may be seen with different clinical presentations in pregnant women. Comorbid diseases are important factors affecting the progression of this disease. In this study, we aimed to evaluate the clinical and laboratory findings in pregnant women with COVID - 19 who had no comorbid disease. METHODS: This retrospective designed study included 217 patients with Covid PCR positive in typically COVID - 19 clinic. The patients were classified into asymptomatic, nonsevere, and severe disease groups. The symptoms, laboratory results, hospital followups and intensive care records of the patients and the findings of new borns are presented. RESULTS: Most of the patients (78%) were in the third trimester of pregnancy, and 103 patients in the study group had severe disease. Fever in the non-severe group and respiratory distress in the severe group were the most common symptoms in the patients. The severe clinical manifestations were specifically observed in the third trimester patients. In the severe group, neutrophil, lactat dehydrogenase, ferritin, CK - MB, IL - 6, and hospital stay were statistically higher than those in other groups (p < 0.05). Increase in BUN and creatine were the most predictive parameters in intensive care admission. While the intensive care unit (ICU) requirement was higher in patients in the severe group, premature birth was observed more frequently in the severe group (p < 0.05) .

A fractional-order model of COVID-19 considering the fear effect of the media and social networks on the community.

Since December 2019, the world has experienced from a virus, known as Covid-19, that is highly transmittable and is now spread worldwide. Many mathematical models and studies have been implemented to work on the infection and transmission risks. Besides the virus's transmission effect, another discussion appears in the community: the fear effect. People who have never heard about coronavirus, face every day uncertain and different information regarding the effect of the virus and the daily death rates from sources like the media, the medical institutions or organizations. Thus, the fear of the virus in the community can possibly reach the point that people become scared and confused about information polluted from different networks with long-term trend discussions. In this work, we use the Routh-Hurwitz Criteria to analyze the local stability of two essential critical points: the disease-free and the co-existing critical point. Using the discretization process, our analysis have shown that one should distinguish between the spread of "awareness" or "fear" in the community through the media and others to control the virus's transmission. Finally, we conclude our theoretical findings with numerical simulations.

Maternal deaths due to COVID-19 disease: The cases in a single center pandemic hospital in the south east of Turkey.

Coronavirus-19 disease is still a pandemic health problem and uncertainty in the management of severe or critically ill pregnant women confuses continually the obstetricians. The nationwide maternal mortality rate due to covid-19 still has not been presented in any study in Turkey. The study includes four maternal mortality cases in a referral single pandemic center in our country. Case 1, a 34-year-old, 34 weeks of gestation with moderate disease. The cesarean section was performed due to nonreassuring nonstress tests. She died on the postpartum seventh day. Case 2, a 37-year-old, at 36 weeks of gestation. The symptoms consisted of dry cough, shortness of breath and labor pain, and 3 cm cervical opening. Her second cesarean section was performed and she died at postpartum ninth day. Case 3, 33 years old, 33 weeks of gestation with moderate/severe stage of the disease. A few days after the treatment, CS was performed due to her severe condition and she died at postpartum 15th day. Case 4, 39 years old, 35 weeks of gestation, she was at a severe stage of the disease. On the second day after the treatment, CS was performed due to her severe condition and she died at postpartum seventh day. The postpartum period after cesarean section should be followed cautiously under the appropriate treatment of the COVID-19 disease. Unfortunately, the reason for this rapid deterioration which we observed in our cases is not well known and appropriate medications and algorithms should be established as soon as possible.

Stability analysis and simulation of the novel Corornavirus mathematical model via the Caputo fractional-order derivative: A case study of Algeria.

The novel coronavirus infectious disease (or COVID-19) almost spread widely around the world and causes a huge panic in the human population. To explore the complex dynamics of this novel infection, several mathematical epidemic models have been adopted and simulated using the statistical data of COVID-19 in various regions. In this paper, we present a new nonlinear fractional order model in the Caputo sense to analyze and simulate the dynamics of this viral disease with a case study of Algeria. Initially, after the model formulation, we utilize the well-known least square approach to estimate the model parameters from the reported COVID-19 cases in Algeria for a selected period of time. We perform the existence and uniqueness of the model solution which are proved via the Picard-Lindelöf method. We further compute the basic reproduction numbers and equilibrium points, then we explore the local and global stability of both the disease-free equilibrium point and the endemic equilibrium point. Finally, numerical results and graphical simulation are given to demonstrate the impact of various model parameters and fractional order on the disease dynamics and control.

Serum TNF-α, IL-1ß, and IL-6 levels in chronic HBV-infected patients.

BACKGROUND: The objective of the study was to evaluate the serum levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 in chronic HBV-infected patients. METHODS: The present study was a single centre, prospective and randomised controlled trial. Twenty healthy volunteers and thirty HBeAg-negative patients with planned liver biopsy and treatment-naive diagnosed with chronic hepatitis B (CHB) were included in the study. TNF-α, IL-1ß and IL-6 levels were measured in the serum of CHB patient and control groups using an ELISA. Results were compared statistically using a Mann-Whitney U test. RESULTS: The mean age of the CHB group (20 men, 10 women) and the control group (10 men, 10 women) was 33.3 ± 9.7 (17-55) and 26.1 ± 12.3 (16-57), respectively. When the two groups were compared with the Mann-Whitney U-test, TNF-α and IL-6 levels were found to be significantly higher in the CHB group compared to the control group (P = .003, P < .0001, respectively). Although IL-1ß levels were not statistically significant, they were higher in the CHB group compared to the controls (P = .07). CONCLUSIONS: The results of our study showed that serum levels of TNF-α and IL-6 are increased in CHB patients.

Fever of unknown origin (FUO) on a land on cross-roads between Asia and Europa; a multicentre study from Turkey.

AIMS: The differential diagnosis of Fever of Unknown Origin (FUO) is still a major clinical challenge despite the advances in diagnostic procedures. In this multicentre study, we aimed to reveal FUO aetiology and factors influencing the final diagnosis of FUO in Turkey. METHODS: A total of 214 patients with FUO between the years 2015 and 2019 from 13 tertiary training and research hospitals were retrospectively evaluated. RESULTS: The etiologic distribution of FUO was infections (44.9%), malignancies (15.42%), autoimmune/inflammatory (11.68%) diseases, miscellaneous diseases (8.41%) and undiagnosed cases (19.62%). Brucellosis (10.25%), extrapulmonary tuberculosis (6.54%) and infective endocarditis (6.54%) were the most frequent three infective causes. Solid malignancies (7.1%) and lymphoma (5.6%), adult-onset still's disease (6.07%) and thyroiditis (5.14%) were other frequent diseases. The aetiological spectrum did not differ in elderly people (P < .05). Infections were less frequent in Western (34.62%) compared with Eastern regions of Turkey (60.71%) (P < .001, OR: 0.31, 95% Cl: 0.19 to 0.60). The ratio of undiagnosed aetiology was significantly higher in elderly people (p: 0.046, OR: 2.34, 95% Cl: 1.00 to 5.48) and significantly lower in Western Turkey (P: .004, OR: 3.07, 95% Cl: 1.39 to 6.71). CONCLUSIONS: Brucellosis, extrapulmonary tuberculosis and infective endocarditis remain to be the most frequent infective causes of FUO in Turkey. Solid tumours and lymphomas, AOSD and thyroiditis are the other common diseases. The aetiological spectrum did not differ in elderly people, on the other hand, infections were more common in Eastern Turkey. A considerable amount of aetiology remained undiagnosed despite the state-of-the-art technology in healthcare services.

Demographic, clinical and laboratory characteristics for differential diagnosis of peripheral lymphadenopathy (LAP) and the etiologic distribution of LAP in adults; a multicenter, nested case-control study including 1401 patients from Turkey.

Peripheral lymphadenopathy (LAP) is an important and common abnormal finding of the physical exam in general medical practice. We aimed to reveal the LAP etiology and demographic, clinical and laboratory variables that may be useful in the differential evaluation of LAP. This multicenter, nested case-control study including 1401 patients between 2014 and 2019 was conducted in 19 tertiary teaching and research hospitals from different regions in Turkey. The ratio of infectious, malign and autoimmune/inflammatory diseases was 31.3%, 5% and 0.3%, respectively. In 870 (62%) of patients had nonspecific etiology. Extrapulmonary tuberculosis (n: 235, 16.8%) was the most frequent cause of LAP. The ratio of infective etiology of LAP was significantly lower in patients older than 65 years-old compared to younger patients with the rate of 66.67% and 83.84%, respectively (p 0.016, OR 0.386, 95% Cl 0.186-0.803). The probability of malign etiology was higher both in patients who are older than 45 years-old (p < 0.001, OR 3.23, 95% Cl 1.99-5.26) and older than 65 years-old (p 0.002, OR 3.36, 95% Cl 1.69-6.68). Age, localization and duration of LAP, leukocytosis, anemia, thrombocytopenia, CRP and sedimentation rate were important parameters to differentiate infections. Size of lymph node and splenomegaly in addition to the parameters above were useful parameters for differentiating malign from benign etiology. Despite the improvements in diagnostic tools, reaching a definite differential diagnosis of lymphadenopathy is still challenging. Our results may help clinicians to decide in which cases they need an aggressive workup and set strategies on optimizing the diagnostic approach of adulthood lymphadenopathy.

Predictive hematological and immunological parameters associated with postpartum progressed Covid-19 disease.

Background: In pregnancy, Coronavirus disease-2019 (COVID-19) infection disease may be more severe due to existing physiological changes. Similarly, changes during and after birth can make the patient more subceptible. Objective: To investigate possible laboratory findings that was related to postpartum progression of COVID-19 disease. Methods: Pregnant women who are pregnant at 28 weeks or more and who are COVID-19 positive at the time of delivery were investigated in this study. Progressed post- delivery and non-progressed COVID-19 positive pregnants' laboratory findings were analyzed. Hematological and immunological parameters associated with postpartum progressed COVID-19 disease were evaluated. Results: Totally 151 individuals were conducted to the study. In the prenatal analysis, higher BMI and lower albumin levels were detected in the progressed group (p<0.05). In the postpartum analysis; White Blood Cell, lymphocyte and albumin were increased, while neutrophil, NLR, LDH, CK, D-DIMER, Ferritin, CRP and IL-6 were decreased in the non-progressed group as opposite of the progressed group (p<005). Conclusion: We observed that prenatal low albumin and high BMI may be related to progression of the COVID-19 disease after delivery. In progressed group, inflammatory markers were increased after delivery while in non-progressed group they were improved. These markers may be warning for the postpartum progression of COVID-19 disease.

A mathematical model of the evolution and spread of pathogenic coronaviruses from natural host to human host.

Coronaviruses are highly transmissible and are pathogenic viruses of the 21st century worldwide. In general, these viruses are originated in bats or rodents. At the same time, the transmission of the infection to the human host is caused by domestic animals that represent in the habitat the intermediate host. In this study, we review the currently collected information about coronaviruses and establish a model of differential equations with piecewise constant arguments to discuss the spread of the infection from the natural host to the intermediate, and from them to the human host, while we focus on the potential spillover of bat-borne coronaviruses. The local stability of the positive equilibrium point of the model is considered via the Linearized Stability Theorem. Besides, we discuss global stability by employing an appropriate Lyapunov function. To analyze the outbreak in early detection, we incorporate the Allee effect at time t and obtain stability conditions for the dynamical behavior. Furthermore, it is shown that the model demonstrates the Neimark-Sacker Bifurcation. Finally, we conduct numerical simulations to support the theoretical findings.

Prognostic value of Golgi P 73 and Beta 2-microglobulin in patients with Viral Hepatitis B.

Previous studies detected higher Golgi protein 73 levels in the serum of patients with chronic liver disease. The Beta-2 microglobulin levels were also observed to be higher in patients with chronic hepatitis B infection compared to the inactive carriers and the protein plays an important role in the response to viral infections. The aim of the present study was to assess the liver fibrosis through non-invasive methods in chronic hepatitis B patients. Three groups were included in the study. The first group comprised of the patients who were admitted to the Infectious Diseases and Clinical Microbiology clinic to undergo a liver biopsy, while the second group included the patients who were admitted inactive hepatitis B carriers. The third group comprised the healthy controls. The Golgi p-73 and Beta-2 microglobulin levels in the plasma were determined using the ELISA method. Beta-2 microglobulin level was highest in the patients group and the difference was statistically significant. No significant difference was observed between the carriers group and the group of healthy controls. The Golgi P-73 values were significantly higher in the patients group in comparison to both other groups. However, the mean Golgi p-73 value was also significantly higher in the carrier group compared to the control group. In patients who are followed up with the diagnosis of chronic hepatitis B and who have undergone biopsies as candidates for treatment, the Beta-2 microglobulin and Golgi p-73 values may be important markers since they indicate the extent of the liver damage.

Analysis of the outbreak of the novel coronavirus COVID-19 dynamic model with control mechanisms.

The mathematical models of infections are essential tools in understanding the dynamical behavior of disease transmission. In this paper, we establish a model of differential equations with piecewise constant arguments that explores the outbreak of Covid-19 including the control mechanisms such as health organizations and police supplements for the sake of controlling the pandemic spread and protecting the susceptible population. The local asymptotic stability of the equilibrium points, the disease-free equilibrium point, the apocalypse equilibrium point and the co-existing equilibrium point are analyzed by the aide of Schur-Cohn criteria. Furthermore and by incorporating the Allee function at time t, we consider the extinction case of the outbreak to analyze the conditions for a strong Allee Effect. Our study has demonstarted that the awareness of the police personal and the management of professional health organizations play a vital role to protect the susceptible class and to prevent the spreading. Numerical simulations are presented to support our theoretical findings. We end the paper by a describtive conclusion.

A rare cause of intermittent respiratory distress and epiphora in the newborn: congenital dacryocystocele.

Congenital dacryocystocele is a malformation of the nasolacrimal system. Most of the cases can be successfully treated with conservative treatment options such as sac massage. Congenital dacryocystoceles with concomitant intranasal cysts causing respiratory distress in the newborns are rarely published. In this case report we presented a 2-week-old newborn with bilateral congenital dacryocystoceles causing intermittent respiratory distress. We discuss the importance of nasal endoscopic treatment and multidisciplinary approach for these rare malformations in the light of the current literature.

Orbital Metastasis of Multiple Myeloma: Case Report.

A 68-year-old woman with a history of multiple myeloma presented to the clinic with pain and vision loss in her right eye. Proptosis was observed in her right eye and eye movements were restricted in all directions. Best corrected visual acuity was 3/10 in her right eye. On biomicroscopic examination, hyperemia and subconjunctival hemorrhage were present. Fundus examination of the right eye revealed optic disc edema and choroidal folds. In magnetic resonance imaging two orbital masses were detected. Based on the patient's history and ocular examination, we evaluated the masses as orbital metastasis of multiple myeloma. Palliative radiotherapy was recommended.

Brucella Infection Associated with Complete Atrioventricular Block.

BACKGROUND: The clinical spectrum of Brucella infection is quite diverse and characterized by multi-system involvement. Patients present with myocarditis, endocarditis, or pericarditis. Infective endocarditis is the most common cardiovascular complication in patients with brucellosis. Although conduction abnormalities are seen in cases with endocarditis, they are reported very rarely in the setting of cardiac Brucella infection. CASE REPORT: An eight and a half-year-old male patient was referred to our clinic due to inadequate response to cotrimaxazole plus streptomycin treatment at the 15th day of admission. Although local hospital records on the patient showed a heart rate of 80 bpm, we determined a heart rate of 46 bpm. The electrocardiogram showed complete atrioventricular (AV) block. The average heart rate was determined as 48 bpm with 24-hour Holter electrocardiogram (ECG) monitoring. The echocardiographic examination showed normal-sized heart chambers and the absence of valvular involvement. An agglutination test for brucellosis was found to be positive with a titer of 1/320. High fever, arthralgia, and splenomegaly regressed following doxycycline plus rifampicin therapy, but there was no improvement in the AV block. A permanent pacemaker was implanted because of the detection of an average heart rate of 48 bpm. CONCLUSION: Because cardiac failure and rhythm abnormalities are reported in the course of Brucella infection and may be associated with significant outcomes, cases with brucellosis should be evaluated carefully in terms of cardiac involvement. This report aims to draw attention to complete AV block as an extremely rare complication of Brucella infection.

Risk factors for infection with colistin-resistant gram-negative microorganisms: a multicenter study.

BACKGROUND: Knowing risk factors for colistin resistance is important since colistin is the only remaining choice for the treatment of infections caused by multi-drug resistant microorganisms. OBJECTIVE: Evaluate risk factors associated with infection by colistin-resistant microorganisms. DESIGN: Retrospective study. SETTING: Tertiary healthcare centers. PATIENTS AND METHODS: An e-mail including the title and purpose of the study was sent to 1500 infec.tious disease specialists via a scientific and social web portal named "infeksiyon dunyasi (infection world)". Demographic and clinical data was requested from respondents. MAIN OUTCOME MEASURE(S): Colistin-resistance. RESULTS: Eighteen infectious disease specialists from twelve tertiary care centers responded to the invitation data was collected on 165 patients, 56 cases (39.9%) and 109 (66.0%) age- and sex-matched controls. The colistin-resistant microorganisms isolated from cases were 29 Acinetobacter baumannii (51.8%), 18 Pseudomonas aeruginosa (32.1%) and 9 Klebsiella spp. Colistin, carbapenem, and quinolone use in the last three months were risk factors for colistin resistance in the univariate analysis. Previous quinolone use in the last three months (P=.003; RR:3.2; 95% Ci:1.5-6,7) and previous colistin use in the last three months (P=.001; RR: 3.6; 95% CI: 1.63-7.99) were significant risk factors in the multivariate analysis. CONCLUSION: Clinicians should limit the use of quinolones and remain aware of the possibility of resistance developing during colistin use. LIMITATIONS: The lack of a heteroresistance analysis on the isolates. no data on use of a loading dose or the use of colistin in combination.

Causative pathogens and antibiotic resistance in diabetic foot infections: A prospective multi-center study.

AIM: Clinical practice guidelines for the management of diabetic foot infections developed by the Infectious Diseases Society of America (IDSA) are commonly used worldwide. The issue of whether or not these guidelines need to be adjusted for local circumstances, however, has seldom been assessed in large prospective trials. METHODS: The Turk-DAY trial was a prospective, multi-center study in which infectious disease specialists from centers across Turkey were invited to participate (NCT02026830). RESULTS: A total of 35 centers throughout Turkey enrolled patients in the trial. Overall, investigators collected a total of 522 specimens from infected diabetic foot wounds for culture from 447 individual patients. Among all isolates, 36.4% were gram-positive organisms, with Staphylococcus aureus the most common among these (11.4%). Gram-negative organisms constituted 60.2% of all the isolates, and the most commonly isolated gram-negative was Escherichia coli (15%). The sensitivity rates of the isolated species were remarkably low for several antimicrobials used in the mild infection group. CONCLUSIONS: Based on our findings, several of the antimicrobials frequently used for empirical treatment, including some also recommended in the IDSA guidelines, would not be optimal for treating diabetic foot infections in Turkey. Although the IDSA guideline recommendations may be helpful to guide empiric antimicrobial therapy of DFIs, they should be adjusted to local conditions.