Morphometric Assessment of Facial Morphology in Infants with Orofacial Clefts up to two Years of Age: A Three-Dimensional Cross-Sectional Study.

OBJECTIVE: To assess modelled facial development of infants with unilateral cleft lip (CL) and cleft lip and palate (UCLP) compared to controls up to two years of age. DESIGN AND PARTICIPANTS: A total of 209 facial images of children (CL: n = 37; UCLP: n = 39; controls: n = 137) were obtained in four age categories (T0 = 0.2-0.5; T1 = 0.6-1.0; T2 = 1.1-1.5; T3 = 1.6-2.0 years) and were evaluated using stereophotogrammetry and geometric morphometry. All patients underwent lip surgery before T0, patients with UCLP underwent palatoplasty (T0, T1 before palatoplasty; T2, T3 after palatoplasty). RESULTS: In patients with CL, the forehead was significantly retracted (p ≤ 0.001), while the supraorbital and ocular regions were prominent (p ≤ 0.001). The oronasal region appeared convex (p ≤ 0.001). The lower lip and chin were non-significantly protruded. In patients with UCLP, a significantly retracted forehead and prominent supraorbital region were apparent (p ≤ 0.001). A retrusive oronasal region (p ≤ 0.001) was observed in the middle face. The chin was anteriorly protruded (p ≤ 0.01). No progression of deviations was found with increasing age. After the first year, a slight improvement in the morphological features became apparent. The shape variability of the clefts and controls overlapped, suggesting a comparable modelled facial development. CONCLUSIONS: The facial morphology of individuals with cleft was comparable to the norm. Shape deviation was apparent in the oronasal region, forehead, and chin, which minimised with increasing age even in complete clefts.

Catalogue of the Diptera (Insecta) of Morocco- an annotated checklist, with distributions and a bibliography.

The faunistic knowledge of the Diptera of Morocco recorded from 1787 to 2021 is summarized and updated in this first catalogue of Moroccan Diptera species. A total of 3057 species, classified into 948 genera and 93 families (21 Nematocera and 72 Brachycera), are listed. Taxa (superfamily, family, genus and species) have been updated according to current interpretations, based on reviews in the literature, the expertise of authors and contributors, and recently conducted fieldwork. Data to compile this catalogue were primarily gathered from the literature. In total, 1225 references were consulted and some information was also obtained from online databases. Each family was reviewed and the checklist updated by the respective taxon expert(s), including the number of species that can be expected for that family in Morocco. For each valid species, synonyms known to have been used for published records from Morocco are listed under the currently accepted name. Where available, distribution within Morocco is also included. One new combination is proposed: Assuaniamelanoleuca (Séguy, 1941), comb. nov. (Chloropidae).

Feasibility and Safety of Continuous Glucose Monitoring in Infants at Risk of Hypoglycemia in a Rooming-in Setting.

Background:Screening of neonatal hypoglycemia uses currently intermittent blood sampling. Continuous glucose monitoring (CGM) allows for tighter glucose control and better comfort for newborns and parents. CGM has previously been used in intensive care setting or blinded to clinicians. Our pilot study uses CGM in real time in rooming-in setting. Methods: CGM was attached within first two hours of life. Low glucose readings were verified to prevent overtreatment. Pairs of sensor readings and corresponding blood glucose measurements were assessed retrospectively. Neurodevelopmental evaluation was performed at 24 months. Results: 44 infants were enrolled. Three had verified hypoglycemia found due to CGM. No patient was below 2 standard deviations in any components of Bayley scales. Median scores were: Cognitive 100, language 86, motor 94. Conclusion: Use of CGM in a rooming-in environment is safe from clinical and neurodevelopmental point of view. Randomized trials are needed to evaluate superiority in longer term outcomes.

A new instrument to personalize ovarian stimulation: results of the CERES study after using a novel gonadotropin - follitropin delta.

: Objective: The aim of the study CERES (CzEch REkovelle real life Study) was to gather experience with the use of a novel gonadotrophine, to evaluate the efficacy of follitropin delta in Czech clinical settings and to compare our results with the clinical trial ESTHER-1. METHODS: Individualized follitropin delta daily dose in µg based on the patient's anti-Müllerian hormone (AMH) level and body weight (AMH < 15 pmol/ L: 12 µg/ d; AMH > 15 pmol/ L: 0.10­0.19 µg/ kg/ d; max. 2 µg/ d). RESULTS: A total of 85 women (aged 24-42 years) was included in the study. The average patients age was 32.9 years, the average body weight was 67.8 kg, and the mean level of AMH was 23.2 pmol/ L. There were initiated 85 controlled ovarian stimulations with follitropin delta and 84 egg collections. Forty patients (47%) had optimal number of retrieved eggs (8-14), 75 patients (88%) had embryotransfer, 10 patients (12%) had no embryo suitable for transfer, 65 patients had single embryo transfer and 10 patients had 2 embryos for transfer. There were reported 37 clinical pregnancies (43.5% cPR - clinical pregnancy rate), 30 live births (35.3% LBR - live birth rate), 3 (3.5%) early moderate ovarian hyperstimulation syndroms (OHSS) and no hospitalization due to the treatment. CONCLUSION: Individualized ovarian stimulation optimizes ovarian response, maintains treatment efficacy and improves safety by reducing OHSS incidence. The results of the Czech population study are fully comparable with the international, randomized, assessor-blinded trial ESTHER-1.

Palatal growth changes in newborns with unilateral and bilateral cleft lip and palate from birth until 12 months after early neonatal cheiloplasty using morphometric assessment.

OBJECTIVES: To compare palatal growth changes in infants with complete unilateral (UCLP) or bilateral (BCLP) cleft lip and palate during the first year of life. MATERIALS AND METHODS: Upper dental arches of 68 neonates with UCLP and BCLP were evaluated using 2D and 3D morphometry based on dental casts obtained in two age categories (T0 before early neonatal cheiloplasty-UCLP 4 ± 3 days, BCLP 6 ± 5 days; T1 before palatoplasty-UCLP 10 ± 2 months, BCLP 12 ± 3 months). RESULTS: Intensive palatal growth was manifested in both directions of the palate. Palatal growth in the anterior direction was not restricted, despite the intercanine (CC´) and anterior (LL´) widths being significantly narrowed in the BCLP group (CC´ p = 0.019, LL´ p = 0.009). The posterior dental arches were significantly enlarged (UCLP p ≤ 0.001; BCLP p ≤ 0.001). The negative effect of cleft severity on palatal length was not confirmed (p = 0.802). Variability of the palate was immense mainly in BCLP infants (T0); however, it decreased in both cleft types, confirming the formative effect of palatal growth leading to alveolar cleft closure (UCLP p ≤ 0.001; BCLP p = 0.006 on the right, 0.005 on the left). CONCLUSIONS: Both analyzed cleft groups (UCLP, BCLP) grew favorably during the first year of life, and the palatal growth was not limited in any direction. CLINICAL RELEVANCE: Geometric morphometry allowed a comprehensive analysis of the palate, which can contribute to the improvement of surgical methods.

Duration of Surgery, Ventilation, and Length of Hospital Stay Do Not Affect Breastfeeding in Newborns After Early Cleft Lip Repair.

OBJECTIVE: There are minimal data available on nutrition after early repair of cleft lip and the factors influencing initiation of breastfeeding. This study assessed the impact of the length of surgery, length of ventilation support, and duration of hospital stay on breastfeeding rates after early cleft lip surgery. DESIGN: This is a prospective observational cohort study comparing 2 hospitals providing early surgical repair of facial clefts from January 2014 to December 2016. Both hospitals are designated as Baby-Friendly Hospitals. Demographic and anthropometric data from mothers and newborns were recorded. SETTING: Tertiary neonatal and pediatric surgery center. PATIENTS: Hospital A: 61 newborns, Hospital B: 157 newborns. INTERVENTIONS: Early (day 5 to 14) cheiloplasty in newborns with cleft lip or cleft lip and palate. MAIN OUTCOME MEASURES: Influence of duration of hospital stay, length of operation, and artificial ventilation on the rate of breastfeeding. RESULTS: Significantly, more newborns were breastfed following early surgical repair of an isolated cleft lip compared to those with both cleft lip and palate, in both hospitals (hospital A 82% vs 0%, P = .0001, hospital B 66% vs 5%, P = .0001). Duration of hospital stay, length of operation, and duration of artificial ventilation did not significantly affect the rate of breastfeeding. CONCLUSIONS: The factors associated with early cleft lip repair (length of operation, length of ventilation support, and duration of hospital stay) do not affect breastfeeding rate.

Three-dimensional development of the palate in bilateral orofacial cleft newborns 1 year after early neonatal cheiloplasty: Classic and geometric morphometric evaluation.

OBJECTIVES: The aim of this study was to assess palatal growth in newborns with complete bilateral cleft lip and palate (cBCLP) and bilateral cleft lip and palate with tissue bridges (BCLP + B) 1 year after early neonatal cheiloplasty (ENC). MATERIAL AND METHODS: The methodology was based on classic and morphometric analysis of dental models of newborns with cBCLP or BCLP + B. These analyses included metric analysis, coherent point drift-dense correspondence analysis, superprojection methods, and multivariate statistics. Dental casts were observed in two age categories, which were compared with each other. The first cast was obtained from each patient before ENC (T0, 5 ± 5 days) and the second one prior to palatoplasty (T1, 12 ± 6 months). RESULTS: Fifty-two dental models obtained from 26 newborns with cBCLP and BCLP + B were evaluated. The results showed that over the 12-month period, alveolar clefts were narrowed in both cleft types due to anterior growth combined with the formative effect of suturing. This was confirmed by decreases in the dimensions of the right (T0 9.93 ± 2.80 mm, T1 6.64 ± 2.43 mm; p ≤ 0.003) and left (T0 10.71 ± 4.13 mm, T1 6.69 ± 4.29 mm; p ≤ 0.003) alveolar clefts in cBCLP patients. Similar reductions in alveolar cleft widths occurred on the left side (T0 11.69 ± 4.75 mm, T1 4.34 ± 2.97 mm; p ≤ 0.001) of BCLP + B patients, while on the right side, which was connected by a combined tissue bridge, there was non-significant narrowing of the alveolar cleft (T0 1.61 ± 1.34 mm, T1 1.04 ± 0.70 mm; p = 0.120). The ENC did not restrict posterior palatal growth, meaning that intertuberosity width was extended in cBCLP (T0 32.80 ± 3.15 mm, T1 35.86 ± 2.80 mm; p ≤ 0.001) and in BCLP + B neonates (T0 34.01 ± 2.15 mm, T1 36.21 ± 2.14 mm; p ≤ 0.004). Width and length measurements in the observed groups showed growth tendencies equivalent to those in noncleft or LOP patients. Palatal variability was greater in neonatal cBCLP, but was reduced during the monitored period, approximating that for BCLP + B. Regions with the most notable palatal growth were located primarily at the premaxilla and at the anterior and partially posterior ends of the maxillary segments. CONCLUSION: Early neonatal cheiloplasty had no negative effect on palatal growth in any direction. There was no reduction in the length or width of the palate during the first year of life, nor was there narrowing of the dentoalveolar arch. The formative effect of the operated lip on the anterior part of the palate was confirmed. This, in combination with the favorable growth, lead to closure of the alveolar cleft.

Continuous glucose monitoring as a screening tool for neonatal hypoglycemia in infants of diabetic mothers.

Objective: To assess the plausibility of using the continuous glucose monitoring as a sole source of data for the screening of the neonatal hypoglycemia.Study design: Infants of mothers with diabetes were screened for neonatal hypoglycemia (less than 2.5 mmol/l after 4 h of life). Initial measurement was performed using point of care analyzer. We applied continuous glucose monitoring system subsequently. Infants were monitored up to 5 days or until discharge.Results: Out of 32 infants 11 had postnatal hypoglycemia resolved within 12 h of life. Two infants had hypoglycemia found due to continuous glucose monitoring after 24 h of life when sufficient feeding was established and they did not show any signs of hypoglycemia. We did not have any false negative measurements. No infant showed clinical signs of neonatal hypoglycemia.Conclusions: Continuous glucose monitoring is plausible and safe to use for screening of neonatal hypoglycemia. It operates well within the range that is accepted as safe for neurodevelopment. In addition, it can be used after first day of life where regular screening ends. Limitation of this method is possible alarm negligence of caregivers.

Three-dimensional assessment of facial asymmetry in preschool patients with orofacial clefts after neonatal cheiloplasty.

OBJECTIVES: To evaluate facial asymmetry changes in pre-school patients with orofacial clefts after neonatal cheiloplasty and to compare facial asymmetry with age-matched healthy controls. METHODS AND MATERIALS: The sample consisted of patients with unilateral cleft lip (UCL), unilateral cleft lip and palate (UCLP), and bilateral cleft lip and palate (BCLP). The patients were divided in two age groups with a mean age of 3 years (n = 51) and 4.5 years (n = 45), respectively, and 78 age-matched individuals as controls. Three-dimensional (3D) facial scans were analyzed using geometric morphometry and multivariate statistics. RESULTS: Geometric morphometry showed positive deviations from perfect symmetry on the right side of the forehead in the intervention groups and the controls. The UCL groups showed the greatest asymmetric nasolabial area on the cleft-side labia and the contralateral nasal tip. The UCLP group showed, moreover, asymmetry in buccal region due to typical maxillar hypoplasia, which was accentuated in the older group. The BCLP groups showed slightly similar but greater asymmetry than the control groups, except for the philtrum region. CONCLUSIONS: Asymmetry of each of the cleft groups significantly differed from the controls. Except for the buccal region in the UCLP and BCLP groups, asymmetry did not significantly increase with age.

Treatment of gynecological cancers diagnosed during pregnancy.

Because of a notable increase in age at delivery, the incidence of malignancy diagnosed during pregnancy has substantially increased. This review aims to summarize the literature and expert knowledge on gynecologic cancers diagnosed in pregnancy regarding epidemiology, examination and staging procedures, description of treatment modalities and management of gynecological malignancies with special interest in cervical and ovarian cancer. Thorough attention is paid to the surgery and chemotherapy administration for early-stage cervical cancer diagnosed during pregnancy.

Microcirculatory blood flow during cardiac arrest and cardiopulmonary resuscitation does not correlate with global hemodynamics: an experimental study.

BACKGROUND: Current research highlights the role of microcirculatory disorders in post-cardiac arrest patients. Affected microcirculation shows not only dissociation from systemic hemodynamics but also strong connection to outcome of these patients. However, only few studies evaluated microcirculation directly during cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). The aim of our experimental study in a porcine model was to describe sublingual microcirculatory changes during CA and CPR using recent videomicroscopic technology and provide a comparison to parameters of global hemodynamics. METHODS: Cardiac arrest was induced in 18 female pigs (50 ± 3 kg). After 3 min without treatment, 5 min of mechanical CPR followed. Continuous hemodynamic monitoring including systemic blood pressure and carotid blood flow was performed and blood lactate was measured at the end of baseline and CPR. Sublingual microcirculation was assessed by the Sidestream Dark Field (SDF) technology during baseline, CA and CPR. Following microcirculatory parameters were assessed off-line separately for capillaries (≤20 µm) and other vessels: total and perfused vessel density (TVD, PVD), proportion of perfused vessels (PPV), microvascular flow index (MFI) and heterogeneity index (HI). RESULTS: In comparison to baseline the CA small vessel microcirculation was only partially preserved: TVD 15.64 (13.59-18.48) significantly decreased to 12.51 (10.57-13.98) mm/mm(2), PVD 15.57 (13.56-17.80) to 5.53 (4.17-6.60) mm/mm(2), PPV 99.64 (98.05-100.00) to 38.97 (27.60-46.29) %, MFI 3.00 (3.00-3.08) to 1.29 (1.08-1.58) and HI increased from 0.08 (0.00-0.23) to 1.5 (0.71-2.00), p = 0.0003 for TVD and <0.0001 for others, respectively. Microcirculation during ongoing CPR in small vessels reached 59-85 % of the baseline values: TVD 13.33 (12.11-15.11) mm/mm(2), PVD 9.34 (7.34-11.52) mm/mm(2), PPV 72.34 (54.31-87.87) %, MFI 2.04 (1.58-2.42), HI 0.65 (0.41-1.07). The correlation between microcirculation and global hemodynamic parameters as well as to lactate was only weak to moderate (i.e. Spearman's ρ 0.02-0.51) and after adjustment for multiple correlations it was non-significant. CONCLUSIONS: Sublingual microcirculatory parameters did not correlate with global hemodynamic parameters during simulated porcine model of CA and CPR. SDF imaging provides additional information about tissue perfusion in the course of CPR.

Early and late operation of cleft lip and intelligence quotient and psychosocial development in 3-7 years.

BACKGROUND: Early and late operations of the cleft lip represent exposure to general anesthesia during the first year of life. The early exposure to the anesthetics may influence long term neurological outcome. Timing of the operation may also influence the quality of life as babies with early repair might be accepted better by their families. AIMS: The aim of the study was to compare outcomes between two groups of patients operated on for the cleft lip in the first year of life. STUDY DESIGN: Observational cohort study. SUBJECTS: Early repair group included patients operated on in the first eight days of life and late repair group those operated on between 3 and 10 months. OUTCOME MEASURES: Intelligence quotient (IQ) and psychosocial development of children who were operated on for cleft lip were compared at the age of 3-7 years. RESULTS: No differences were found between early (n=15) and late (n=17) repair group in terms of IQ. In both IQ was within the normal range: 100.00 (SD 13.867), 98.76 (SD 10.109), respectively. Significantly better results in physical functioning (P=0.042) and self-esteem (P=0.014) concepts in early repair group were found. CONCLUSIONS: We compared outcomes of two groups of patients operated on for cleft lip in the first year of life. The earlier anesthesia did not show a negative impact on intelligence quotient in 3-7 years compared to later anesthesia. The earlier repair of the cleft lip showed a significant positive impact on psychosocial development in 2 out of 13 concepts tested.

Experience with real time continuous glucose monitoring in stabilising fluctuating glycaemia during intensive care of the preterm infant of a diabetic mother.

OBJECTIVE: The newborns of diabetic mothers suffer from perinatal complications more frequently than the newborns of healthy women. METHODS: We used for 7 days a real time continuous glucose monitoring system (RT-CGMS) to monitor glucose homeostasis and manage glucose administration in a premature newborn of a diabetic mother. RESULTS: The boy was born at 35 + 5 gestational weeks with typical signs of diabetic fetopathy. RT-CGMS revealed 2 late hypoglycaemia episodes on the 2nd and 4th days. The sensor readings correlated well with glycaemia measured in the laboratory (r = 0.908, p = 0.005). To support conclusions of this case report, we attached the data of five other preterm newborns of diabetic mothers who were later successfully treated according to the RT-CGMS data as well. CONCLUSIONS: This approach allows timely response to glycaemia instability and is applicable even in preterm infants.

Delayed delivery of a twin - a hazard or an acceptable method? Prospective study.

OBJECTIVE: To examine the possibility of postponement of the delivery of fetus B after preterm delivery or late abortion of fetus A in multiple pregnancy. METHODS: Between January 2000 and September 2010, we tried to delay delivery of the second twin in 18 cases. Group A includes women that experienced a preterm premature rupture of the membranes in fetus A (PPROM), group B includes women who presented with regular uterine activity and the vaginal finding indicated unavoidable late miscarriage or preterm delivery. RESULTS: Thirteen (72.22%) of the 18 attempts were evaluated as unsuccessful. The interval of delay of delivery of fetus B ranged between 24 and 384 hours. Five cases were successful. CONCLUSION: Indication for applying this therapeutic procedure to a pregnant woman must be strictly selective. The procedure will be also in future more or less reserved for women in which subsequent pregnancy is for different reasons highly improbable.

Keratin 8 sequence variants in patients with pancreatitis and pancreatic cancer.

Keratin 8 (KRT8) is one of the major intermediate filament proteins expressed in single-layered epithelia of the gastrointestinal tract. Transgenic mice over-expressing human KRT8 display pancreatic mononuclear infiltration, interstitial fibrosis and dysplasia of acinar cells resulting in exocrine pancreatic insufficiency. These experimental data are in accordance with a recent report describing an association between KRT8 variations and chronic pancreatitis. This prompted us to investigate KRT8 polymorphisms in patients with pancreatic disorders. The KRT8 Y54H and G62C polymorphisms were assessed in a cohort of patients with acute and chronic pancreatitis of various aetiologies or pancreatic cancer originating from Austria (n=16), the Czech Republic (n=90), Germany (n=1698), Great Britain (n=36), India (n=60), Italy (n=143), the Netherlands (n=128), Romania (n=3), Spain (n=133), and Switzerland (n=129). We also studied 4,234 control subjects from these countries and 1,492 control subjects originating from Benin, Cameroon, Ethiopia, Ecuador, and Turkey. Polymorphisms were analysed by melting curve analysis with fluorescence resonance energy transfer probes. The frequency of G62C did not differ between patients with acute or chronic pancreatitis, pancreatic adenocarcinoma and control individuals. The frequency of G62C varied in European populations from 0.4 to 3.8%, showing a northwest to southeast decline. The Y54H alteration was not detected in any of the 2,436 patients. Only 3/4,580 (0.07%) European, Turkish and Indian control subjects were heterozygous for Y54H in contrast to 34/951 (3.6%) control subjects of African descent. Our data suggest that the KRT8 alterations, Y54H and G62C, do not predispose patients to the development of pancreatitis or pancreatic cancer.

A degradation-sensitive anionic trypsinogen (PRSS2) variant protects against chronic pancreatitis.

Chronic pancreatitis is a common inflammatory disease of the pancreas. Mutations in the genes encoding cationic trypsinogen (PRSS1) and the pancreatic secretory trypsin inhibitor (SPINK1) are associated with chronic pancreatitis. Because increased proteolytic activity owing to mutated PRSS1 enhances the risk for chronic pancreatitis, mutations in the gene encoding anionic trypsinogen (PRSS2) may also predispose to disease. Here we analyzed PRSS2 in individuals with chronic pancreatitis and controls and found, to our surprise, that a variant of codon 191 (G191R) is overrepresented in control subjects: G191R was present in 220/6,459 (3.4%) controls but in only 32/2,466 (1.3%) affected individuals (odds ratio 0.37; P = 1.1 x 10(-8)). Upon activation by enterokinase or trypsin, purified recombinant G191R protein showed a complete loss of trypsin activity owing to the introduction of a new tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis. In conclusion, the G191R variant of PRSS2 mitigates intrapancreatic trypsin activity and thereby protects against chronic pancreatitis.

Haplotype block structure study of the CFTR gene. Most variants are associated with the M470 allele in several European populations.

An average of about 1700 CFTR (cystic fibrosis transmembrane conductance regulator) alleles from normal individuals from different European populations were extensively screened for DNA sequence variation. A total of 80 variants were observed: 61 coding SNSs (results already published), 13 noncoding SNSs, three STRs, two short deletions, and one nucleotide insertion. Eight DNA variants were classified as non-CF causing due to their high frequency of occurrence. Through this survey the CFTR has become the most exhaustively studied gene for its coding sequence variability and, though to a lesser extent, for its noncoding sequence variability as well. Interestingly, most variation was associated with the M470 allele, while the V470 allele showed an 'extended haplotype homozygosity' (EHH). These findings make us suggest a role for selection acting either on the M470V itself or through an hitchhiking mechanism involving a second site. The possible ancient origin of the V allele in an 'out of Africa' time frame is discussed.