Effects of Pasturella Multocida B:2 and its immunogens (LPS and OMP) on reproductive hormones in Nili-Ravi Buffaloes

Livestock is a fundamental part of the agriculture industry in Pakistan and contributes more than 11.53% to GDP. Among livestock species, the buffaloes are regarded as the black gold of Pakistan. Being the highest milk producers globally, Nili-Ravi buffaloes are the most famous ones. Buffaloes are affected by many endemic diseases, and "Hemorrhagic septicemia" (HS) is one of them. This study was designed to ascertain the effects of experimental exposure ofP. multocida B:2 (oral) and its immunogens, i.e., LPS (oral and intravenous) and OMP (oral and subcutaneous) on reproductive hormonal profiles in Nili-Ravi buffaloes. Repeated serum samples were collected from the jugular vein of experimental animals for 21 days (0, 02, 04, 08, 12, 16, 20, 24, 36, 48, 72, 120, 168, 216, 264, 360, 456 and 504 hours). Hormonal assays to determine the serum concentrations of Gonadotropin-releasing hormone (GnRH), Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Estrogen (E2) and progesterone (P4) were performed using (MyBioSource) commercial Elisa kits. The hormonal profile of all treatment groups of the buffalo heifers exhibited significant (P<0.05) variations as compared to the control group (G-1). These results indicate suppression in Nili-Ravi buffaloes' reproductive hormonal profile on exposure to P. multocida B:2 and its immunogens. This influence warrants that exposure to H.S may be a possible reason for delayed puberty and poor reproduction performance in Nili-Ravi buffaloes.

Effects of increased ambient temperature and supplemental altrenogest prior to pregnancy establishment in gilts

Heat stress (HS) mitigation strategies are critically needed to combat the substantial economic effects on animal agriculture. The manifestations of seasonal infertility include delayed puberty onset, reduced conception rates, decreased litter size, and increased wean to estrus interval. To assess the effects of HS during early gestation and evaluate a benefit of supplemental altrenogest (ALT) as a mitigation strategy, thirty crossbred post-pubertal gilts (157 ± 11 kg) were subjected to estrous synchronization via 14 d oral administration of ALT. Artificial insemination during estrus was performed and gilts were then placed into one of four treatment groups; heat stress (HS; 35 ± 1 οC for 12h/31.60 ± 1 οC for 12h) with (HSALT, n = 7) or without (HSCON, n = 7) 15 mg/d ALT supplementation or thermal neutral (TN; 20 ± 1 οC) conditions with (TNALT, n = 8) or without (TNCON, n = 8) 15 mg/d ALT supplementation until 12 d post-estrus (dpe). Administrating ALT occurred at 0600 h from 3-12 dpe and rectal temperatures (TR) and respiration rates (RR) were recorded. Blood was collected via jugular venipuncture on 0, 4, 8 and 12 dpe. Gilts were euthanized humanely at 12 dpe followed by collection of ovarian tissue, and uterine flushing for conceptus collection. In HS compared to TN gilts, RR and TR were increased (P &lt; 0.01) but unaffected by ALT supplementation. Feed intake (FI) was reduced (P &lt; 0.01) by HS but unaltered by ALT treatment. Corpora lutea (CL) weight was reduced (P &lt; 0.01) in HSCON gilts when compared to TNCON and HSALT gilts despite progesterone (P4) concentrations in serum and luteal tissue not being affected by treatment (P ≥ 0.10). CL diameter was reduced (P ≤ 0.05) in HSALT gilts compared to other treatments. Interleukin-1β (IL1B) uterine flush concentration was not affected (P &gt; 0.20) by environment or ALT supplementation, although moderate (P = 0.06) interaction between environment and ALT existed, as IL1B concentration in TNALT was increased (P = 0.03) compared to TNCON gilts. While environment did not affect conceptus development (P = 0.90), ALT supplementation advanced conceptus elongation (P &lt; 0.01). Collectively, these data demonstrate that HS may affect luteal development prior to pregnancy establishment, and ALT increases conceptus elongation by12 dpe.

Phenotypic spectrum of patients with mutations in CHD7: clinical implications of endocrinological findings

Objective: Heterozygous CHD7 mutations cause a broad spectrum of clinical phenotypes ranging from typical CHARGE syndrome to self-limited delayed puberty. This study aimed to investigate the clinical characteristics of endocrine dysfunction in patients with CHD7 mutations. Methods: The clinical features and endocrine findings from 30 patients with CHD7 variants were retrospectively reviewed. A diagnosis of CHARGE syndrome was based on the Verloes diagnostic criteria. Results: Seventeen patients fulfilled the criteria for typical CHARGE syndrome, one patient for partial/incomplete CHARGE, and the remaining 11 patients had atypical CHARGE syndrome. One patient was diagnosed with Kallmann syndrome and unilateral deafness. The most frequently observed features were inner ear anomalies (80.0%), intellectual disability (76.7%), and external ear anomalies (73.3%). The mean height and weight SDSs at diagnosis were -2.6 ± 1.3 and -2.2 ± 1.8, respectively. Short stature was apparent in 18 patients (60%), and one patient was diagnosed with growth hormone deficiency. Seventeen males showed genital hypoplasia, including micropenis, cryptorchidism, or both. Seven patients after pubertal age had hypogonadotropic hypogonadism with hyposmia/anosmia and olfactory bulb hypoplasia. Truncating CHD7 mutations were the most common (n = 22), followed by missense variants (n = 3), splice-site variants (n = 2), and large deletion (n = 2). Conclusions: A diverse phenotypic spectrum was observed in patients with CHD7 variants, and endocrine defects such as short stature and delayed puberty occurred in most patients. Endocrine evaluation, especially for growth and pubertal impairment, should be performed during diagnosis and follow-up to improve the patient’s quality of life.

Hypogonadism in male infants and adolescents: new androgen formulations

Background Male hypogonadism may be associated with micropenis and cryptorchidism in newborn, absent or incomplete pubertal development when it occurs during childhood. During puberty, androgen replacement therapy plays a pivotal role in subjects with hypogonadism to induce sexual maturation, growth acceleration, anabolic effects on fat-free mass growth increasing muscle strength, directly and indirectly on the attainment of peak bone mass in young men. Moreover, in newborns with congenital hypogonadism, androgen therapy could be effective to increase genital size. Summary Testosterone replacement therapy (TRT) represents the cornerstone of the management of hypogonadism in boys. During puberty, replacement therapy needs to be modulated with gradual dosing increase to better mimic the physiologic pubertal development. Currently, intramuscular testosterone esters (in particular testosterone enanthate, TE) and subcutaneous testosterone pellets are the only formulations approved by the US Food and Drug Administration (FDA) for delayed puberty, while no preparation is approved for long-term use in the adolescent age. Several new testosterone (T) formulations (as transdermal, nasal, subcutaneous, and oral formulation) are recently developed to improve the pharmacokinetic profile and to ease the administration route increasing patient compliance in adult males with hypogonadism. All these formulations are not approved for pediatric age, although some of them are used as “off-label” regimens. This special issue is aimed to illustrate new T formulations and their potential role as replacement therapy in the pediatric population, as well as to highlight investigational areas to contribute to health care improvement in these patients. Key Messages. Despite the lack of evidence-based guidelines regarding the choice of T formulation in the pediatric population, new formulations appear to have a potential role for TRT in adolescent age. They have been designed for adult age with a little flexibility of dosage, although a few formulations may be attractive for pubertal induction and penile enlargement thanks to their greater flexibility and easing of administration. On the other hand, long-acting and stable formulations could meet post-pubertal needs, increasing TRT compliance in a critical phase as the adolescent age. Further controlled, long-term safety, and efficacy studies for all these new T formulations within the pediatric population are needed.

Body image, self-perception and satisfaction among girls with Turner syndrome-A prospective cross-sectional study

Objectives Delayed puberty & short stature in girls with Turner syndrome(TS) can lead to low body image, self-esteem & satisfaction. We aimed to evaluate body image, self-perception, and satisfaction among girls with TS using Multi-Dimensional Body Image Self Relations Questionnaire -Appearance Scale (MBSRQ-AS). Methods Patients with karyotype-proven diagnosis of TS between 15-21 years were included after they achieved final adult height. We used MBSRQ-AS instrument with 5 sub-scales: Appearance Evaluation(AE), Appearance Orientation(AO), Body Areas Satisfaction Scale(BASS), Overweight Preoccupation(OWP) and Self Classified Weight(SCW) sub-scales. Mean scores were compared to available sex matched population norms & compared between different sub-cohorts. Results Of 59 eligible girls, 37 girls agreed to participate with mean age : 17.35 ±1.6 years. Turner girls had significantly lower scores compared to sex-matched population norms in AO [mean(SD): 3.32(0.42) vs 3.91(0.6)]; (p&lt;0.001) and SCW [mean(SD): 3.26(0.71) vs 3.57(0.73); (p=0.01)] sub-scales. In contrast, they had slightly higher scores in BASS [ mean(SD): 3.38(0.74) vs 3.23(0.74); (p=0.23)] & OWP [mean(SD): 3.12(0.39) vs 3.03(0.96); (p=0.21)] sub-scales though not statistically significant. Girls with classic 45 X karyotype and those who were overweight/obese had lower scores in AE & AO sub-scales compared to normal population (p&lt;0.05). Conclusion Compared to sex-matched population norms, Turner girls are not reporting negative effects due to their appearance & report general satisfaction with most areas of their body; however, Turner girls with classic karyotype or who were obese/overweight were generally unhappy with their physical appearance. They also seem to not focus their attention on their appearance.

New and consolidated therapeutic options for pubertal induction in hypogonadism: in-depth review of the literature

Delayed puberty (DP) defines a retardation of onset/progression of sexual maturation beyond the expected age due to either a lack/delay of the hypothalamo-pituitary-gonadal (HPG) axis activation or a gonadal failure. DP usually gives rise to concern and uncertainty in patients and their families, potentially affecting their immediate psychosocial well-being and also creating longer-term psychosexual sequelae. The most frequent form of DP in younger teenagers is self-limiting and may not need any intervention. Conversely, DP due to hypogonadism requires prompt and specific treatment that we summarize in this review. Hormone therapy primarily targets genital maturation, development of secondary sexual characteristics and the achievement of target height in line with genetic potential, but other key standards of care include body composition and bone mass. Finally, pubertal induction should promote psychosexual development and mitigate both short- and long-term impairments comprising low self-esteem, social withdrawal, depression and psychosexual difficulties. Different therapeutic options for pubertal induction have been described for both males and females but we lack the necessary larger randomized trials to define the best approaches for both sexes. We provide an in-depth and updated literature review regarding therapeutic options for inducing puberty in males and females, particularly focusing on recent therapeutic refinements that better encompass the heterogeneity of this population, and underlining key differences in therapeutic timing and goals. We also highlight persistent shortcomings in clinical practice, wherein strategies directed at “the child with delayed puberty of uncertain aetiology” risk being misapplied to older adolescents likely to have permanent hypogonadism.

Whole exome sequencing identifies deleterious rare variants in CCDC141 in familial self-limited delayed puberty

Developmental abnormalities of the gonadotropin-releasing hormone (GnRH) neuronal network result in a range of conditions from idiopathic hypogonadotropic hypogonadism to self-limited delayed puberty. We aimed to discover important underlying regulators of self-limited delayed puberty through interrogation of GnRH pathways. Whole exome sequencing (WES) data consisting of 193 individuals, from 100 families with self-limited delayed puberty, was analysed using a virtual panel of genes related to GnRH development and function (n = 12). Five rare predicted deleterious variants in Coiled-Coil Domain Containing 141 (CCDC141) were identified in 21 individuals from 6 families (6% of the tested cohort). Homology modeling predicted all five variants to be deleterious. CCDC141 mutant proteins showed atypical subcellular localization associated with abnormal distribution of acetylated tubulin, and expression of mutants resulted in a significantly delayed cell migration, demonstrated in transfected HEK293 cells. These data identify mutations in CCDC141 as a frequent finding in patients with self-limited delayed puberty. The mis-localization of acetylated tubulin and reduced cell migration seen with mutant CCDC141 suggests a role of the CCDC141-microtubule axis in GnRH neuronal migration, with heterozygous defects potentially impacting the timing of puberty.

Study Tanner staging of β- thalassemic patients attending thalassemic Center in Ibn Al-Atheer Teaching Pediatric Hospital

Purpose: determine any relationship between tanner staging of the patients and transfusion program, iron overload and chelation therapy and study tanner staging of β- thalassemic patients attending Thalassemic Center in Ibn Al-Atheer Teaching Pediatric Hospital. Patients and Methods: A descriptive-analytic study (case series study) was done on β- thalassemic patients attending Thalassemia Center in Ibn Al- Atheer Teaching Hospital in Mosul, during the period from the 1st of January to the 30th of June 2019.Sixty patients with β- thalassemia, 45 of them are β- thalassemia major cases and 15 are β- thalassemia intermedia cases. The patients of the major type were sub-classified into 3 groups according to their ages: Group 1, Patients from the age of ≥ 13 years; Group 2, Patients from the age of 14 years to 16 years and Group 3, Patients from the age of more than 17 years. Results: current study showed male (77.78, 66.67) % more than female (22.22; 33.33) % in both types of thalassemia (Major and Intermedia) respectively.so the most of the patients in this study live in urban areas (58.33%) and (41.67%) in rural areas, mean age at diagnosis of thalassemia major was 7.16 months, Delayed tanner staging was found in 64.44% of patients with thalassemia major, while in thalassemia intermedia only 33.33% were considered to be on a delayed stage. as well as 4(80%) of Tanner Stage (II) for pateints in age group (≥ 13) years compare to 20% for stage (III), so 50% for both stage (II and III) respectively in age group (14-16) years. Conclusion: Two-third of the patients with thalassemia major had delayed puberty (64.44%), while one- third of the patients with thalassemia intermedia had delayed pubertal development (33.33%).