Author constructions: Drs Aifen Wang and Weidong Hu contributed to this article equally. Conceptualization, Aifen Wang and Weidong Hu; Methodology, Aifen Wang and Youguo Chen; Investigation, Aifen Wang; Writing – Original Draft, Aifen Wang, Weidong Hu, Jinsong Yang and Huiping Guo; Writing – Review & Editing, Aifen Wang, Jinsong Yang and Ziyue Zhang; Supervision, Aifen Wang and Youguo Chen.Disclosure statement: All authors declared no competing interests.SARS-CoV-2 was first noted in December 2019 in Wuhan, Hubei, China. The World Health Organization reported that more than 1,699,595 people had contracted COVID-19 and 106,138 people had died of SARS-CoV-2 on 12 April 2020. Men are more likely to contract COVID-19 than women.1-4 Limited evidence is available to identify whether pregnant women are susceptible to contracting COVID-19. However, in Soochow city, Jiangsu, where 10,625,700 residents live, the first patient with COVID-19 was confirmed on January 22, 2020. Between January 1 and March 31, 2020, 87 persons were confirmed as the COVID-19 infection. No new cases have been reported since February 18, 2020. All patients with COVID-19 were discharged on 10 March 2020. There was a total of 23493 pregnant women who did not contract COVID-19 and delivered their babies in hospitals, except for one pregnant woman who delivered by cesarean section in Soochow Fifth Hospital Affiliated to Soochow University, which is a designated hospital for COVID-195. In this report, we present our experience of the protection of pregnant women in an epidemic area.In Soochow, Jiangsu, all hospitals have developed detailed guidelines for protecting pregnant women since January 22, 2020. We have protective actions for pregnant women who had traveled from outside of Soochow city (algolithm1) and pregnant women suspected of COVID-19 infection (algolithm2). We take different levels of protective actions based on the status of patients. The first level of protective action are staff who wear surgical caps, surgical face masks, disposable coveralls and surgical gloves; the second level are staff who wear surgical caps, protective goggles, N95 face masks, disposable coveralls, surgical gloves, and shoe covers; and the third level of protective action are staff who wear surgical caps, face shields, N95 face masks, disposable coveralls, surgical gloves, and shoe covers. In Soochow city, everyone is obligated to apply for Health Code, which is two-dimensional barcodes based on travel history and possible signs of COVID-19, such as fever, dry cough, chest stress, and dyspnea, which were confirmed by physicians since February 22, 2020. The three codes are red code, yellow code, and green code. Red code is given to people who have traveled from a severe epidemic area or have not terminated the quarantine phase. Yellow code means people who live with someone who is in a quarantine room and has dry cough, fever and dyspnea. Green code is meant for people with no signs of COVID-19. People with red code have to be in the hospital or stay in a quarantine room for 14 days. People with yellow code should be in a quarantine room for seven days. People with red code or yellow code are suggested against being in public areas. All people are obligated to have Health Code and are involved in credit management. For those who need to stay in the hospital, all people, including patients and staff, are mandated to put on a face mask, whether symptomatic or not. At the entrance of the hospital and each ward, temperature monitoring is required for everyone, even staff. Only single rooms are provided for one patient and one visitor in the obstetrical ward. In the designated hospital, “fever clinic” is extremely effective in excluding patients suspected of COVID-19. When pregnant patients have fever, they will be consulted by physicians from the “fever clinic” as soon as possible. These patients will receive RT-PCR and immunoglobin tests for COVID-19 within two hours. All non-urgent gynecologic surgeries were suspended on January 25, 2020 and have resumed on March 23, 2020 due to uncontrolled COVID-19. In our community, we have volunteers that check the status of Health code to monitor people who have yellow or red code.Society of Obstetrics and Gynecology, Soochow, have taken measures in response to the COVID-19 outbreak. Substantial online education on protective actions for pregnant women was implemented for each obstetrician. Apps like WeChat and hotline have been set up for pregnant women to counsel their symptoms. Patients with abnormal complaints have received attention quickly. However, we still do not have efficient management of pregnant women with COVID-19. Due to extreme precautions, pregnant women were not profoundly affected by COVID-19 in Soochow.

Background: The COVID-19 pandemic represents one of the most stressful events of recent times. Among the population, healthcare professionals who treat COVID-19 patients are most likely to develop psychological distress and posttraumatic stress symptoms (PTSS). The present study thus aimed to investigate the psychological impact of the COVID-19 outbreak on Italian healthcare workers. Methods: The responses of 145 healthcare workers (72 medical doctors and 73 nurses) were included in the final dataset. Participants were asked to provide sociodemographic and clinical information, and to complete: 1) quality of life and health-related Visual Analogue Scales, 2) State-Trait Anxiety Inventory-Form Y1, 3) Beck Depression Inventory, and 4) PTSD Checklist for DSM-5. Results: A comparison between healthcare professionals working in COVID-19 wards and other units revealed that the former reported higher levels of both depressive symptoms and PTSS. Moreover, the results of regression analyses showed that in healthcare professionals working with COVID-19 patients, gender and marital status, and gender and age significantly predicted depressive symptoms and PTSS, respectively. Particularly, being female and not in a relationship were found to be associated with higher levels of depressive symptoms, whereas being female and older were found to be related to higher levels of PTSS. Conclusions: The current findings suggest that specific predisposing factors could identify healthcare workers who are at high risk of developing mental health symptoms when faced with COVID-19 patients.

Rationale, aims and objectives: This study was designed to evaluate intraoperative case irrelevant communications (CICs) by content, initiator, recipient and interference via a real-time operative room analysis Method: The CICs in the operative room across a purposive sample of 52 surgical procedures were evaluated as recorded by a tripod-capable camera in the operative room in this prospective observational study. The CICs were evaluated by initiator, recipient and interference. Results: Overall 106 CIC events were recorded across 52 operations (2.03/operation). Most (35.8%) of CICs referred to irrelevant comment by context, while 28.3% of CICs referred to other patients. Individually, external personnel (24.5%) were the most likely initiators of a CIC, while surgical group was most likely initiator (28.3%) of as well recipient (49.0%) of CIC. Overall every CIC interfered with surgical work-flow, by distracting more than one member of the team in 34.9% of cases, only one member of the team in 33.0% of cases and the entire team in 14.1% of cases for a long-term. Conclusions: In conclusion, this real-time operative room analysis revealed CICs to be mainly referred to small talk or other patients for case co-ordination and organization, while emphasize the particular role of external staff as the most likely initiator of CICs and operating and assisting surgeons as the most likely initiator and receiver of CICs. Our findings seem to indicate the majority of intraoperative CICs to interfere with surgical work-flow by causing a long-term distraction in at least one member of the operative room team.

Monocyte subset analysis by flow cytometry has been shown to be a useful diagnostic tool in chronic myelomonocytic leukemia in adults. An increase in the classical monocyte fraction (CD14++/CD16-) greater than 94.0% of total monocytes is considered highly sensitive and specific in distinguishing CMML from other myeloproliferative disorders. In a pilot study of juvenile myelomonocytic leukemia cases, we noted that CD14++/CD16- monocyte fraction was >95% in de novo JMML with somatic PTPN11 mutations but normal in those with monosomy 7 or Noonan syndrome. Monocyte subgroup profiling by itself is not diagnostic of JMML but may distinguish molecular subgroups within JMML.

A 57 year old lady with no underlying structural heart disease presented with recurrent episodes of paroxysmal palpitation with documented adenosine responsive narrow QRS tachycardia. 12 lead surface electrocardiograms showed no pre-excitation. She underwent an electrophysiology (EP) study. Anterograde study demonstrated dual AV physiology. A regular narrow QRS tachycardia similar to clinical tachycardia was induced in the EP study with atrial pacing protocols. Ventricular overdrive pacing (VOD) was performed during the tachycardia. What are the circuits involved in the tachycardia?

To the Editor,We have read with great interest the article entitled ‘Management of Patients with Interrupted Inferior Vena Cava Requiring Electrophysiology Procedures’ by Hanley et al1 in the latest issue of the journal. We would like to thank the authors for their difficult case series with interrupted vena cava inferior and for successfully performed electrophysiologic studies. Electrophysiologic procedures including mapping and percutaneous catheter ablation of left-sided accessory pathways via the retrograde transaortic approach have been successfully applied techniques in patients with supraventricular tachycardia with and without Wolff-Parkinson-White electrocardiographic pattern for a long time.2 If no anatomic obstacles are found, a deflectable mapping catheter can easily be advanced from the femoral artery and positioned in the mitral annulus to localize the accessory pathway, even in patients with congenital anomalies.3 One should keep in mind that the retrograde transaortic approach has the potential adverse events related to percutaneous arterial access and tight contact with valvular leaflets although it seems as a simpler and less time consuming approach requiring less specialized equipment compared to the transseptal way.Mapping and percutaneous catheter ablation of the atrioventricular node or the His bundle can also be performed from the left side via the retrograde transaortic approach. Some electrophysiologists prefer the retrograde transaortic route as a first-line approach although most operators perform catheter ablation from the venous side.The electrophysiologists’ preferences are generally based on experience, familiarity with the equipment and the procedure, and personal thoughts about the patient.Keywords: ablation; left-sided; retrograde transaortic approach

ABSTRACT Background and Purpose: Abnormal hepatic insulin signaling is a cause or consequence of hepatic steatosis. DPP-4 inhibitors might be protective against fatty liver. We previously reported that the systemic inhibition of insulin receptor (IR) and IGF-1 receptor (IGF1R) by the administration of OSI-906 (linsitinib), a dual IR/IGF1R inhibitor, induced glucose intolerance, hepatic steatosis, and lipoatrophy in mice. In the present study, we investigated the effects of a DPP-4 inhibitor, linagliptin, on hepatic steatosis in OSI-906-treated mice. Experimental Approach: We treated C57BL/6J male mice either with vehicle, linagliptin, OSI-906 or OSI-906 + linagliptin for 7 days. We also conducted proteomic and phosphoproteomic analyses of the liver from those mice. Key Results: Unlike high-fat diet-induced hepatic steatosis, OSI-906-induced hepatic steatosis is not characterized by elevations in inflammatory responses or oxidative stress levels. Linagliptin improved OSI-906-induced hepatic steatosis via an insulin-signaling-independent pathway, without altering glucose levels, free fatty acid levels, gluconeogenic gene expressions in the liver, or visceral fat atrophy. Hepatic quantitative proteomic and phosphoproteomic analyses revealed that perilipin-2 (PLIN2), major urinary protein 20 (MUP20), cytochrome P450 2b10 (CYP2B10), nicotinamide N-methyltransferase (NNMT), and sirtuin families are possibly involved in the process of the amelioration of hepatic steatosis by linagliptin. Conclusion and Implications: Linagliptin improved hepatic steatosis induced by IR and IGF1R inhibition via a previously unknown mechanism that did not involve gluconeogenesis, lipogenesis, or inflammation, suggesting the non-canonical actions of DPP-4 inhibitors in the treatment of hepatic steatosis under insulin-resistant conditions.

Background: The aim of the current study was to investigate and track the SARS-CoV-2 in Iranian Coronavirus Disease 2019 (COVID-19) patients using molecular and phylogenetic methods. Methods: We enrolled seven confirmed cases of COVID-19 patients for the phylogenetic assessment of the SARS-CoV-2 in Iran. The nsp-2, nsp-12, and S genes were amplified using one-step RT-PCR and sequenced using Sanger sequencing method. Popular bioinformatics software were used for sequences alignment and analysis as well as phylogenetic construction. Results: The mean age of the patients in the present study was 60.42±9.94 years and 57.1% (4/7) were male. The results indicated high similarity between Iranian and Chinese strains. We could not find any particular polymorphisms in the assessed regions of the three genes. Phylogenetic trees by neighbor-joining and maximum likelihood method of nsp-2, nsp-12, and S genes showed that there are not any differences between Iranian isolates and those of other countries. Conclusion: As a preliminary phylogenetic study in Iranian SARS-CoV-2 isolates, we found that these isolates are closely related to the Chinese and reference sequences. Also, no sensible differences were observed between Iranian isolates and those of other countries. Further investigations are recommended using more comprehensive methods and larger sample sizes.

Abstract Aim: Off-label drug use in neonates remains a global problem. The retrospective, multicenter study was to study the rates and reasons of off-label drug use among representative NICUs in Henan, China. Methods: Prescriptions were randomized sampled from eight NICUs. Patient characteristics and diseases were collected. Classifications of off-label drug use including age, frequency, dose, indication and route of administration were analyzed. Results: 1770 neonates sampled from eight NICUs were evaluable in the study, with a mean body weight 2.98 kg (SD = 0.80, range 0.78-6.0), 92.03% of whom were exposed to ≥ 1 off-label prescription. 5813 prescriptions with 113 drugs were registered, 84.62% of which were off label. 63.03% of the off-label use was in relation to age. Conclusion: Off-label drug use among neonates remains fairly prevalent in Henan, China. Initiative and effective implementation is urgently required to improve this situation.

Background and Purpose: Heart failure can reflect impaired contractile function at the myofilament level. In healthy hearts, myofilaments become more sensitive to Ca2+ as cells are stretched. This represents a fundamental property of myocardium that contributes to the Frank-Starling response, although the molecular mechanisms underlying the effect remain unclear. Mavacamten is a drug that binds to myosin, which is under investigation as a potential therapy for cardiovascular disease. We tested how mavacamten affects the sarcomere-length dependence of Ca2+-sensitive isometric contraction to determine how mavacamten might modulate the Frank-Starling mechanism. Experimental Approach: Multicellular preparations from the left ventricular free wall of hearts procured from organ donors were chemically permeabilized and Ca2+-activated in the presence or absence of 0.5 μM mavacamten at 1.9 or 2.3 µm sarcomere length (37°C). Isometric force and frequency-dependent viscoelastic myocardial stiffness measurements were made. Key Results: At both sarcomere lengths, mavacamten reduced maximal force and Ca2+-sensitivity of contraction. In the presence and absence of mavacamten, Ca2+-sensitivity of force increased as sarcomere length increased. This suggests that the length-dependent activation response was maintained in human myocardium, even though mavacamten reduced Ca2+-sensitivity. There were subtle effects of mavacamten reducing force values under relaxed conditions (pCa 8.0), as well as slowing myosin cross-bridge recruitment and speeding cross-bridge detachment under maximally activated conditions (pCa 4.5). Conclusion and Implications: Mavacamten did not eliminate sarcomere length-dependent increases in the Ca2+-sensitivity of contraction in myocardial strips from organ donors at physiological temperature. Pharmaceuticals that modulate myofilament function may be useful therapies for cardiovascular disease.

Infective endocarditis and vertebral osteomyelitis are rare infections, most commonly caused by methicillin-sensitive Staphylococcus aureus (MSSA). The eustachian valve is an embryological remnant of the inferior vena cava that has the potential to harbor a nidus leading to infective endocarditis. Eustachian valve endocarditis has been documented in the literature on less than 50 occasions and has yet to be documented in the presence of concomitant vertebral osteomyelitis. In this case, we present a 43-year-old African American male presenting with vertebral osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA). Persistent bacteremia prompted the identification of a vegetative growth on a eustachian valve remnant. This case helps mend the gap in the literature by documenting the treatment considerations in a patient with eustachian valve endocarditis in the presence of osteomyelitis caused by MRSA.

At the date of writing this editorial, there is growing agreement amongst experts that the first wave of the COVID-19 pandemic is in decline. The number of deaths reported each day is now around 1% of the cumulative total and falling. In general, the approach to predicting pandemic policy has been through a comparison of inter-country performance in managing this crisis. While all countries are paying a high price in economic slowdown and lives lost, the health consequences in terms of cases and deaths have varied considerably. Countries with lower relative mortality and infection numbers have shown a more structured logical approach to pandemic management. There is a very real urgency to learn lessons immediately given the pressure to reduce the home confinement policy as soon as possible. While this is clearly a challenging time for policy makers, public health messaging is often emotive around concepts such ‘being at war’ with the virus, and other similar statements. We propose that a more rational approach to moving forward is required to avoid a second wave. Understanding this rational approach can be found through an evaluation of not only how other countries are approaching this challenge, but also from history.

COVID-19 is characterized by fever, cough, shortness of breath, myalgia, and headache. The disease also takes a more severe form with life-threatening manifestations of acute respiratory distress syndrome (ARDS), acute cardiac injury, acute kidney injury, disseminated intravascular coagulopathy, and cytokine storm. It has been elucidated that like its predecessor, the SARS CoV, the SARS CoV-2 utilizes the ACE2 receptor to enter cells. This knowledge brought into speculation the effects of a dysregulated Renin-Angiotensin system (RAS) in the pathogenesis of COVID-19. It has been proposed that the effects of a dysregulated RAS would lead to an inflammatory cascade and contribute to the cytokine storm that is central to the disease. This paper looks at the RAS pathway and the hypothesizes the possibility of a positive RAS feedback loop in the pathogenesis of COVID-19. We also propose possible drug targets for the treatment of COVID-19.

Numerous studies have been carried out over the years to substantiate the claims that Nigella sativa oil or Kalonji oil has immune-modulatory properties and has a positive effect on diverse conditions resulting from deficiencies or abnormalities of the immune system. In this review article, few clinical trials have been looked into in order to determine the specific effects of NS on the immune system and whether the existing literature is substantive.

Abstract In recent years, immune checkpoint therapy to reverse NK and T cell exhaustion has emerged as a promising treatment in various cancers. Recently, the FDA has approved anti-PD-1 pembrolizumab for patients with recurrent or metastatic cervical cancer. Other checkpoint molecules, such as TIGIT and Tim-3 have yet to be fully explored in this disease. Here, we found that PD-1, TIGIT, and Tim-3 are over-expressed on some peripheral blood CD56dim and CD56bright NK cells and T cells in cervical cancer patients and women with premalignant lesions. However, we observed stronger significance and separation between groups when these three molecules were examined together. These cells, with an apparently “exhausted” phenotype, were significantly augmented in patients. Different PD-1 levels (PD1low, PD1int, PD-1hi) on T cells were used to further define checkpoint positive populations. Soluble PD-L1 was observed to be increased in cervical cancer. Within the cancer group, the highest levels of sPD-L1 and triple positive or double positive cells and tumor stage were found similarly within tumors of different stages. Our results might show an overview of what is happening in patients with precancerous lesions and cervical cancer, and may give an early clue as to whom to administer monoclonal checkpoint blocking therapies.

Allergic airway disorders such as asthma and allergic rhinitis are mainly caused by inhaled allergen-induced improper activation and responses of immune- and non-immune cells. One important response is the production of IL-27 by macrophages and dendritic cells (DCs) during the early stage of airway allergies. IL-27 exerts powerful modulatory influences on the cells of innate immunity [e.g., neutrophils, eosinophils, mast cells, monocytes, macrophages, dendritic cells (DCs), innate lymphoid cells (ILCs), natural killer (NK) cells and NKT-cells)] and adaptive immunity (e.g. Th1-, Th2-, Th9-, Th17-, regulatory T-, CD8+ cytotoxic T- and B-cells). The IL-27-mediated signaling pathways may be modulated to attenuate asthma and allergic rhinitis. In this review, a comprehensive discussion concerning the roles carried out by IL-27 in asthma and allergic rhinitis was provided, while evidences are presented favouring the use of IL-27 in the treatment of airway allergies.

A peer-reviewed article of this Preprint also exists. Journal: Biomedicine & PharmacotherapyDOI:  https://doi.org/10.1016/j.biopha.2020.110982 The pathogenesis of Coronavirus disease 2019 is still obscure, indeed it’s only few months since it has been first reported on December 2019, yet the need for exploration of possible mechanisms, suggestion of new drugs should never be delayed. In this communication, the author proposes an integrated pathophysiological as well as pharmacological COVID-19 approach to recommend using anti-inflammatory drugs, other than glucocorticoids, suggesting ibuprofen as an example, to be added to his recently published suggested COVID-19 early management protocol. A possible explanation for the potential failure of hydroxychloroquine for COVID-19 is also explained according to the suggested concept. The author is fully aware of the ibuprofen contradictory hypothesis; as discussed and argued against in this report.

Introduction: WHO has considered Major Congenital Anomalies (MCA) as a recognizable cause of morbidity and mortality in infants and children under five years of age. Method: This is a descriptive study of antenatal MCA over 10 years period from January 2009 to December 2018. All data were analyzed statistically using STATA software (Stata Corporation, College Station, TX). Results: During the study period, there were 147563 patients. Of which, 1502 cases found to have major congenital anomalies, among them 947 (63.05 %) fetuses with isolated major anomalies and 555 cases (36.95%) with MCA. The average antenatal prevalence of MCA for 10 years was 10.1 per 1000 pregnancies. The mean gestational age during the first visit was 27(5.5) weeks with range from 10 to 40 weeks. The maternal age was 30 (6.0) years. Coexisting maternal factors were observed in 481 (32%) of patients including gestational diabetes (8.8%), maternal age (6.59%) and recurrent early pregnancy loss (7.12%). Nervous system was the most common (29%) abnormalities observed and cardiothoracic system (24.9%) was the second most common. Perinatal outcomes showed that 9.6 % had early neonatal death, 19% had still births and 4 % had neonatal death. The perinatal mortality rate was 32.6% among fetuses with major congenital anomalies. Conclusions: The prevalence of major congenital anomalies in our papulation is double the international figures. This study emphasizes the need of national surveillance system and database for congenital anomalies and efforts should be focused in rising awareness of the occurrence and risk factors of congenital anomalies.

Gene drives in malaria control: What we need to know aReagan Mudziwapasi*, bMunyaradzi Christopher Changara, aAbigarl Ndudzo, bTinotenda Kaseke, Farai Godobo, cRyman Shoko, dFanuel Songwe, aSakhile Ndlovu and bSandra Sibonani MlamboaDepartment of Crop and Soil Sciences (Applied Biotechnology Program), Lupane State University, P. O. Box 170, Lupane, ZimbabwebDepartment of Biotechnology, Chinhoyi University of Technology, P. O. Box 7724, Chinhoyi, ZimbabwecDepartment of Biology, Chinhoyi University of Technology, P. O. Box 7724, Chinhoyi, ZimbabwedDepartment of Biosciences and Biotechnology, Midlands State University, P. Bag 9055 Senga Road, Gweru, Zimbabwe  *Corresponding author: reaganmudziwapasi@yahoo.com

Full genome analysis of a young girl with deafness, dystonia, central hypomyelination, refractory seizure, and fluctuating liver function impairment revealed a heterozygous, de novo variant in the BCAP31 gene on chromosome X28q (NC_000023.11(BCAP31_v001):c.92G>A), mutations of which caused the X-linked recessive severe neurologic disorder DDCH (Deafness, Dystonia, and Cerebral Hypomyelination, OMIM#300475). Reverse transcription-PCR (RT-PCR) of the patient’s white blood cells showed the absence of wild-type BCAP31 mRNA but the presence of two novel BCAP31 mRNAs. The major alternatively-spliced mRNA is due to exon 2 skipping and the utilization of a new initiation site in exon 3 that leads to a frameshift and truncated transcript while the minor novel mRNA has a 110 nucleotide insertion to exon 2. Phasing studies showed that the de novo variant arose in the paternal X chromosome. X chromosome inactivation assay was done and confirmed that the patient’s maternal X chromosome was preferentially inactivated, providing evidence that the mutated BCAP31 gene was the predominantly expressed. According to the ACMG guideline, this variant is deemed “pathogenic” (PS2, PS3, PM2, PP3, PP4) and deleterious. This is the first reported female patient in BCAP31-related syndrome resulted from skewed X-inactivation and a de novo mutation in the active X chromosome.

Although parathyroid tissue auto-transplantation is useful for preventing hypoparathyroidism during thyroidectomy, hyperparathyroidism may occur due to proliferation of the transplanted parathyroid tissue. Hyperparathyroidism due to the autografted parathyroid gland should be suspected in patients who undergone parathyroid auto-transplantation.

Adenoid Cystic Carcinoma (AdCC) is a malignant tumor mostly occurring in the head and neck salivary glands. In this article, two rare cases of adenoid cystic carcinoma occurring in the buccal mucosa with their treatment and long-term follow-up are presented.

Premature ovulation may occur during controlled ovarian stimulation. Usually, this is noticed and treatment is canceled before ovum pick up (OPU). In this case, a 24-year-old woman naturally conceived during the stimulation and OPU was successfully performed afterwards. Despite developing severe ovarian hyperstimulation syndrome, she delivered a healthy baby.

Pregnancy provides optimal opportunities for health promotion and disease prevention. Smoking before and during pregnancy is one of the largest modifiable risk factors for a range of adverse pregnancy outcomes. Concerns over the risks of smoking motivate many pregnant smokers to quit. However, most of their partners continue to smoke throughout pregnancy. More than one-third (35%) of men in the world smoke, and just over 6% of women do (Ritchie et al. Published online at OurWorldInData.org 2020). The impact of paternal smoking, second-hand or third-hand smoking on the perinatal health is largely overlooked. Given the vast majority of studies focusing on the pregnant smokers, less is known about paternal smoking on their future children.In this paper (Zhou et al. BJOG 2020), using a large national prepregnancy registry database, Zhou et al. found that paternal smoking may be associated with birth defects such as congenital heart diseases, limb abnormalities and neural tube defects in the offspring. The result was consistent with previous retrospective studies, but a medium to large effect size was seen. All of the odd ratios exceeded 2.5, with one even over 20 (congenital heart diseases OR=2.51, 95%CI 1.04-6.05; limb abnormalities OR=20.64 95%CI 6.46-68.02; digestive tract anomalies OR=3.67 95%CI 1.44-9.37; neural tube defect OR=4.87,95%CI 1.66-14.28). Such difference might be partially explained by potential confounding factors. For example, the extent of tobacco exposure, in the National Birth Defects Prevention Study (Malik et al. Pediatrics 2008; 121: e810), compared with light smoking exposure (<14 cigarettes per day), heavy smoking women (≥25 cigarettes per day) were more likely to have infants with septal defects (OR 2.06; 95%CI: 1.20-3.54), suggesting a dose-dependent relationship between tobacco exposure and birth defects.In addition, a reduced risk of birth defects after changing smoking behaviors was found in Zhou’s paper. It is no surprise that paternal smoking cessation could improve the adverse outcomes. Limited evidences address whether there is a critical window period by which smoking must be stopped to prevent subsequent adverse perinatal outcomes. Results from a retrospective case-control study indicated that the risk of fetal congenital heart diseases increased as women smoked during the first trimester (Sullivan et al. J Pediatr; 2015; 166:978). In a prospective cohort study (McCowan et al. BMJ 2009; 338: b1081), the authors concluded that stopping smoking early in pregnancy, and certainly by 15-16 weeks’ gestation, may minimize the adverse effects of smoking on late pregnancy complications and should be an important goal for pregnant smokers. Yet, such critical time for paternal smoking cessation remains unknown.Tobacco smoke is also a human germ cell mutagen. It is estimated that with even a modest 25% increase in sperm mutation frequency caused by smoke-exposure, for each generation across the global population there will be millions of smoking-induced de novo mutations transmitted from father to offspring (Beal et al. Mutation Research;2017; 773:26).Therefore, it is strongly recommended that women and men should immediately stop smoking in advance of reproduction.No disclosures: A completed disclosure of interest form is available to view online as supporting information.